Prevention of Postoperative Events following Reversal with Sugammadex or Neostigmine (the P-PERSoN Trial): Pilot Data Following Early Termination of a Prospective, Blinded, Randomised Trial

Benjamin Olesnicky, Matthew Doane, Clare Farrell, Greg Knoblanche, Anthony Delaney, Benjamin Olesnicky, Matthew Doane, Clare Farrell, Greg Knoblanche, Anthony Delaney

Abstract

Background: Residual paralysis following anaesthesia is common and can lead to postoperative morbidity. While sugammadex has been shown to be effective in minimising residual paralysis, uncertainty exists as to whether its use reduces any associated morbidity. We designed this trial to determine if the use of sugammadex for the reversal of intraoperative aminosteroid neuromuscular blockade results in improvements in postoperative pulmonary complications, complications in the recovery unit, postoperative nausea and vomiting, and patient satisfaction, when compared to reversal with neostigmine.

Methods: A prospective, double-blind, randomised controlled trial in adult patients admitted for surgical operations at two Australian hospitals between December 2018 and March 2019 was performed comparing the reversal of neuromuscular paralysis using sugammadex 2 mg/kg versus neostigmine 50mcg/kg. Statistical analysis of continuous data was performed using two tailed t-tests, with categorical and ordinal data being assessed by chi-squared analysis.

Results: The trial was terminated due to a combination of resource constraints and the 2019 novel coronavirus disease (COVID-19) pandemic. Of 51 patients screened, 33 were eligible for participation and 30 subsequently recruited and randomised. All patients received the intended treatment allocated. Data for the primary outcome was obtained in all patients. There was no difference in the rates of postoperative pulmonary complications between the sugammadex and neostigmine groups (0% (0/19) vs 9% (1/11) RR 5.0 (95% CI 0.22-113) p=0.37. There was no difference in any of the secondary outcomes between the groups.

Conclusions: The P-PERSoN trial showed no difference in postoperative pulmonary complications between sugammadex and neostigmine based reversal of aminosteroid neuromuscular block, but was underpowered to show any difference due to early trial termination. The randomisation and data collection was feasible. We support the need for an adequately resourced and funded randomised controlled trial to address this important clinical question.

Conflict of interest statement

The authors declare that there are no conflicts of interest.

Copyright © 2022 Benjamin Olesnicky et al.

Figures

Figure 1
Figure 1
CONSORT flowchart for the P-PERSoN trial.

References

    1. Bissinger U., Schimek F., Lenz G. Postoperative residual paralysis and respiratory status: a comparative study of pancuronium and vecuronium. Physiological Research . 2000;49(4):455–462.
    1. Murphy G. S., Szokol J. W., Marymont J. H., Greenberg S. B., Avram M. J., Vender J. S. Residual neuromuscular blockade and critical respiratory events in the postanesthesia care unit. Anesthesia & Analgesia . 2008;107(1):130–137. doi: 10.1213/ane.0b013e31816d1268.
    1. Murphy G. S., Szokol J. W., Franklin M., Marymont J. H., Avram M. J., Vender J. S. Postanesthesia care unit recovery times and neuromuscular blocking drugs: a prospective study of orthopedic surgical patients randomized to receive pancuronium or rocuronium. Anesthesia & Analgesia . 2004;98(1):193–200. doi: 10.1213/01.ane.0000095040.36648.f7.
    1. Berg H., Roed J., Viby-Mogensen J., et al. Residual neuromuscular block is a risk factor for postoperative pulmonary complications. a prospective, randomised, and blinded study of postoperative pulmonary complications after atracurium, vecuronium and pancuronium. Acta Anaesthesiologica Scandinavica . 1997;41(9):1095–1103. doi: 10.1111/j.1399-6576.1997.tb04851.x.
    1. Cammu G. V., Smet V., de Jongh K., Vandeput D. A prospective, observational study comparing postoperative residual curarisation and early adverse respiratory events in patients reversed with neostigmine or sugammadex or after apparent spontaneous recovery. Anaesthesia & Intensive Care . 2012;40(6):999–1006. doi: 10.1177/0310057x1204000611.
    1. Booij L. H. D. J. Cyclodextrins and the emergence of sugammadex. Anaesthesia . 2009;64:31–37. doi: 10.1111/j.1365-2044.2008.05868.x.
    1. Ledowski T., Hillyard S., O’Dea B., Archer R., Vilas-Boas F., Kyle B. Introduction of sugammadex as standard reversal agent: impact on the incidence of residual neuromuscular blockade and postoperative patient outcome. Indian Journal of Anaesthesia . 2013;57(1):p. 46. doi: 10.4103/0019-5049.108562.
    1. Brueckmann B., Sasaki N., Grobara P., et al. Effects of sugammadex on incidence of postoperative residual neuromuscular blockade: a randomized, controlled study. British Journal of Anaesthesia . 2015;115(5):743–751. doi: 10.1093/bja/aev104.
    1. Kotake Y., Ochiai R., Suzuki T., et al. Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block. Anesthesia & Analgesia . 2013;117(2):345–351. doi: 10.1213/ane.0b013e3182999672.
    1. Togioka B. M., Yanez D., Aziz M. F., Higgins J. R., Tekkali P., Treggiari M. M. Randomised controlled trial of sugammadex or neostigmine for reversal of neuromuscular block on the incidence of pulmonary complications in older adults undergoing prolonged surgery. British Journal of Anaesthesia . 2020;124(5):553–561. doi: 10.1016/j.bja.2020.01.016.
    1. Kheterpal S., Vaughn M. T., Dubovoy T. Z., et al. Sugammadex versus neostigmine for reversal of neuromuscular blockade and postoperative pulmonary complications (stronger): a multicenter matched cohort analysis. Anesthesiology . 2020;132(6):1371–1381. doi: 10.1097/aln.0000000000003256.
    1. Kirmeier E., Eriksson L. I., Lewald H., et al. Post-anaesthesia pulmonary complications after use of muscle relaxants (popular): a multicentre, prospective observational study. Lancet Respiratory Medicine . 2019;7(2):129–140. doi: 10.1016/S2213-2600(18)30294-7.
    1. Li G., Freundlich R. E., Gupta R. K., et al. Postoperative pulmonary complications’ association with sugammadex versus neostigmine: a retrospective registry analysis. Anesthesiology . 2021;134(6):862–873. doi: 10.1097/aln.0000000000003735.
    1. The National Health and Medical Research Council tARCaUA. National Statement on Ethical Conduct in Human Research . Sydney, Australia: Commonwealth of Australia bank; 2007.
    1. (ICH) ICfHoTRfPfHU. Integrated addendun to ICH E6(R1): guideline for good clinical practice. .
    1. Olesnicky B. L. D. M., Farrell C., Knoblanche G., Delaney A. Prevention of postoperative events following reversal with sugammadex or neostigmine (the P-PERSoN trial) – pilot data following early termination of a prospective, blinded, randomised trial. .
    1. Mazo V., Sabate S., Canet J., et al. Prospective external validation of a predictive score for postoperative pulmonary complications. Anesthesiology . 2014;121(2):219–231. doi: 10.1097/aln.0000000000000334.
    1. Jammer I., Wickboldt N., Sander M., et al. Standards for definitions and use of outcome measures for clinical effectiveness research in perioperative medicine: European perioperative clinical outcome (EPCO) definitions: a statement from the ESA-ESICM joint taskforce on perioperative outcome measures. European Journal of Anaesthesiology . 2015;32(2):88–105. doi: 10.1097/eja.0000000000000118.
    1. Stark P. A., Myles P. S., Burke J. A. Development and psychometric evaluation of a postoperative quality of recovery score: the QoR-15. Anesthesiology . 2013;118(6):1332–1340. doi: 10.1097/aln.0b013e318289b84b.
    1. Apfel C. C., Laara E., Koivuranta M., Greim C. A., Roewer N. A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers. Anesthesiology . 1999;91(3):p. 693. doi: 10.1097/00000542-199909000-00022.
    1. Jerath A., Austin P. C., Wijeysundera D. N. Days alive and out of hospital: validation of a patient-centered outcome for perioperative medicine. Anesthesiology . 2019;131(1):84–93. doi: 10.1097/aln.0000000000002701.
    1. Myles P. S., Shulman M. A., Heritier S., et al. Validation of days at home as an outcome measure after surgery: a prospective cohort study in Australia. BMJ Open . 2017;7(8) doi: 10.1136/bmjopen-2017-015828.e015828
    1. Schulz K. F., Altman D. G., Moher D., Group C. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ . 2010;340:p. c332. doi: 10.1136/bmj.c332.

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