Respiratory muscle activity after spontaneous, neostigmine- or sugammadex-enhanced recovery of neuromuscular blockade: a double blind prospective randomized controlled trial

Abstract

Background: The use of neostigmine after neuromuscular blockade (NMB) has been associated with postoperative respiratory complications. In previous studies, we found lower diaphragmatic activity after neostigmine reversal of NMB, compared to sugammadex. It is still unclear whether the adequate use of neostigmine guarantees normal respiratory muscle function after NMB. In this study, we wanted to assess the effect of commonly used degrees of NMB and their possible reversal strategies on respiratory muscle activity after the return of normal neuromuscular transmission.

Methods: This is a randomized, controlled, parallel-group, single-centre, double-blind study in patients scheduled for intracranial surgery at a tertiary academic hospital in Belgium. All participants received target controlled propofol/remifentanil anesthesia and were randomized into one of five groups, receiving either a shallow NMB with no reversal (shallow/saline), a shallow NMB with sugammadex reversal (shallow/sugammadex), a moderate NMB with neostigmine reversal (moderate/neostigmine), a moderate NMB with sugammadex reversal (moderate/sugammadex), or a deep NMB with sugammadex reversal (deep/sugammadex). Primary and secondary outcome parameters were diaphragm and intercostal electromyographic (EMG) activity at the moment of resumed spontaneous breathing activity, defined as a maximal interval of 10 min after the first spontaneous breath.

Results: For the five groups, a total of 55 patients could be included in the final analysis. Median time of spontaneous breathing analyzed was 5 min (IQR 3-9.5 min). Both the moderate/sugammadex and the moderate/neostigmine groups had lower levels of diaphragm EMG compared to the shallow/sugammadex group. The moderate/neostigmine group had lower levels of intercostal EMG activity compared to the shallow/saline group.

Conclusions: In this study, the depth of neuromuscular blockade and type of reversal strategy impacts respiratory muscle activity at the moment of resumed spontaneous breathing and recovery of neuromuscular blockade. Both groups that received moderate NMB had lower levels of diaphragm EMG, compared to the shallow NMB group with sugammadex reversal. Compared to the shallow NMB group with no reversal, the moderate NMB with neostigmine reversal group had lower intercostal EMG activity.

Trial registration: Clinicaltrials.gov NCT01962298 on October 9, 2013 and EudraCT 2013-001926-25 on October 10, 2013.

Keywords: Neostigmine; Neuromuscular blockade; Neuromuscular blocking agents; Respiratory outcome; Sugammadex.

Conflict of interest statement

TS and VS have received research grants from Merck & Co / MSD. TS has received travel funding from Merck & Co / MSD. All other authors have no conflicts of interest related to this article.

Figures

Fig. 1

Sample of unfiltered EMG data. Top curve (“P3”) shows the pressure/flow signal, indicating inspiratory and expiratory flow. The following 5 curves show the raw EMG per set of leads for the diaphragm and the intercostal muscles. Bottom 5 show amplitudes of these raw signals. To obtain these data, electrodes are positioned bilaterally on the chest wall, on the mid-axillary and midclavicular lines just below the costal margins. The intercostal electrodes are positioned on the mid-clavicular line as well. Changes in electrical currents are measured in between a pair of electrodes, with a reference electrode positioned on the sternum. Currents flowing from the two right and left sided electrodes were labeled aR Dia and aL Dia, those in between the electrodes on the midclavicular line aF Dia, and those placed laterally aD Dia. The final data combined the signals from left and right

Fig. 2

Simplified CONSORT flowchart. Legend: NMB: neuromuscular block