Neuromuscular Block in Patients 80 Years and Older

A Prospective, Controlled Study

Denis Schmartz; Raouf Sghaier; Paul Bernard; Jean Francois Fils; Thomas Fuchs-Buder


BMC Anesthesiol. 2021;21(225) 

In This Article


The research protocol was approved by the institutional review committee (Comité de Protection des Personnes EST III, 10 September 2018, referral number 200, chairperson Pr Y. Martinet) and registered at (NCT03551652 on 29/05/2018) before enrollment of the first patient. All patients gave written informed consent, and all clinical data were obtained in our department. 35 patients scheduled for a surgical procedure under general anesthesia were included between 15 May 2020 and 16 March 2021. Exclusion criteria were hypersensitivity to rocuronium or any other of the drugs used during this study, contraindication to rocuronium, planned rapid sequence induction (RSI), refusal to participate, and the absence of written informed consent. This study is reported according to the STROBE statement.

Patients were included in one of two groups based on age: an elderly cohort in group 80+ (≥ 80 years old) and a younger cohort in group 20–50 (age 20–50 years).

Anesthesia Technique

Monitoring established on arrival in the operating room included electrocardiography, non-invasive arterial pressure, pulse oximetry, and capnography. After preoxygenation, total intravenous anesthesia (TIVA) was induced in all patients with 1.5–2.5 mg/kg propofol and 10 μg sufentanil and maintained with 4–10 mg/kg/h propofol and bolus doses of sufentanil (5–10 μg). Nitrous oxide and halogenated agents were avoided. Neuromuscular block was established with a single dose of rocuronium 0.6 mg/kg without any further injection. The bolus of rocuronium was given over 5 s. By using a warming blanket, the central temperature was maintained over 35 °C and the peripheral body temperature measured at the thenar eminence of the palm was maintained at least at 32° C. End tidal pressure of carbon dioxide was maintained between 32–36 mm Hg.

Neuromuscular Monitoring

Neuromuscular blockade was quantified with TOFscan (IMED, Marseille, France) according to Good Clinical Research Practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents.[13] This device has an adapter with a built-in three-dimensional acceleration transducer applying a constant preload. The TOFScan hand adapter was fixed on the dominant hand and surface electrodes were placed on the cleaned skin over the corresponding ulnar nerve as described previously.[14] The negative electrode was placed near the wrist and the positive electrode 3 cm proximally and the arm and fingers were secured with velcro straps to prevent movement artifacts during stimulation. Neuromuscular monitoring was started after induction of anesthesia but before administration of rocuronium. The current intensity was fixed at 50 mA. To obtain raw TOF ratio's the T4/T2 algorithm of the device was inactivated. After some initial TOF stimulation, a 5 s, 50 Hz tetanic stimulation was applied followed by TOF stimulations for 10–15 min until a stable response was achieved—defined as less than 5% variation in the TOF-ratio for at least 2 min. Thereafter the device was set to deliver TOF stimulations at a 15 s interval and the following time intervals were measured as defined: onset time, defined as the time from start of injection of rocuronium to no response to TOF stimulation (TOF count = 0); clinical duration defined as the time from start of injection of rocuronium to the return of the 4th response of the TOF (TOF count = 4) and recovery to the TOF-ratio of 0.9 and 1.0, defined as the time from start of injection of rocuronium to a TOF ratio above 0.9 and 1.0, respectively. For each time interval, the first of three consecutive corresponding values were considered. In addition, the deepest level of neuromuscular block during onset was also quantified.


Recovery to a TOF ratio ≥ 0.9 was the primary endpoint of this study. Secondary outcomes were onset time, maximum depth of neuromuscular block, clinical duration and recovery to a TOF ratio ≥ 1.0.

Statistical Analysis

A sample size estimation was done to detect a difference of at least 30% in the recovery to a TOF ratio ≥ 90%. Under intravenous anesthesia mean time to a TOF ratio recovery ≥ 0.9 for adult patients is 60 min with a standard deviation of 11 min.[15] With an alpha risk of 5% and a power of 90%, 14 patients needed to be included in each group. In order to compensate for possible dropouts, 35 patients were included in total.

When continuous variables were compared between 2 groups, the assumptions in the t-test, i.e. homogeneity of variances and normality of residuals were tested by the Bartlett's test of homogeneity of variances and the Shapiro-Wilks test for the normality of the residuals. If the underlying assumptions were met, a t-test was performed, and data are presented as mean ± standard deviation; if not, a nonparametric Wilcoxon rank test was used and data are presented as median and interquartile range. Discrete variables were compared using a Pearson Chi-square test. When paired differences were tested for continuous variables, a t-test for paired data was used on variables for which a normal distribution is observed for the difference between the two variables and data are presented as mean ± standard deviation. Otherwise, a Wilcoxon test for paired data was used and median and inter-quartile range are presented.