Lidocaine combined with magnesium sulfate preserved hemodynamic stability during general anesthesia without prolonging neuromuscular blockade: a randomized, double-blind, controlled trial

Waynice N Paula-Garcia, Gustavo H Oliveira-Paula, Hans Donald de Boer, Luis Vicente Garcia, Waynice N Paula-Garcia, Gustavo H Oliveira-Paula, Hans Donald de Boer, Luis Vicente Garcia

Abstract

Background: Lidocaine and magnesium sulfate have become increasingly utilized in general anesthesia. The present study evaluated the effects of these drugs, isolated or combined, on hemodynamic parameters as well as on the cisatracurium-induced neuromuscular blockade (NMB).

Methods: At a university hospital, 64 patients, ASA physical status I and II, undergoing elective surgery with similar pain stimuli were randomly assigned to four groups. Patients received a bolus of lidocaine and magnesium sulfate before the tracheal intubation and a continuous infusion during the operation as follows: 3 mg.kg- 1 and 3 mg.kg- 1.h- 1 (lidocaine - L group), 40 mg.kg- 1 and 20 mg.kg- 1.h- 1 (magnesium - M group), equal doses of both drugs (magnesium plus lidocaine - ML group), and an equivalent volume of isotonic solution (control - C group). Hemodynamic parameters and neuromuscular blockade features were continuously monitored until spontaneous recovery of the train of four (TOF) ratio (TOFR > 0.9).

Results: The magnesium sulfate significantly prolonged all NMB recovery features, without changing the speed of onset of cisatracurium. The addition of lidocaine to Magnesium Sulfate did not influence the cisatracurium neuromuscular blockade. A similar finding was observed when this drug was used alone, with a significantly smaller fluctuation of mean arterial pressure (MAP) and heart rate (HR) measures during anesthesia induction and maintenance. Interestingly, the percentage of patients who achieved a TOFR of 90% without reaching T1-95% was higher in the M and ML groups. Than in the C and L groups. There were no adverse events reported in this study.

Conclusion: Intravenous lidocaine plays a significant role in the hemodynamic stability of patients under general anesthesia without exerting any additional impact on the NMB, even combined with magnesium sulfate. Aside from prolonging all NMB recovery characteristics without altering the onset speed, magnesium sulfate enhances the TOF recovery rate without T1 recovery. Our findings may aid clinical decisions involving the use of these drugs by encouraging their association in multimodal anesthesia or other therapeutic purposes.

Trial registration: NCT02483611 (registration date: 06-29-2015).

Keywords: General anesthesia; Hemodynamic parameters; Lidocaine; Magnesium sulfate; Neuromuscular blockade.

Conflict of interest statement

Hans D. de Boer received research grants from Merck and is treasurer of the ERAS Society.

Figures

Fig. 1
Fig. 1
Flow chart of patient participation. C: control group; M: magnesium sulfate group; ML: magnesium sulfate combined with lidocaine group
Fig. 2
Fig. 2
Area under the curve (AUC) of hemodynamic parameters. a AUC of the mean arterial pressure (MAP) in the induction period. b AUC of the MAP during the maintenance period. c AUC of heart rate (HR) in the induction period. d AUC of HR during the maintenance period. C: control group; M: magnesium sulfate group; ML: magnesium sulfate combined with lidocaine group. Values are the mean change and 95% CI

References

    1. Herroeder S, Schonherr ME, De Hert SG, Hollmann MW. Magnesium--essentials for anesthesiologists. Anesthesiology. 2011;114(4):971–993. doi: 10.1097/ALN.0b013e318210483d.
    1. Weibel S, Jokinen J, Pace NL, Schnabel A, Hollmann MW, Hahnenkamp K, Eberhart LH, Poepping DM, Afshari A, Kranke P. Efficacy and safety of intravenous lidocaine for postoperative analgesia and recovery after surgery: a systematic review with trial sequential analysis. Br J Anaesth. 2016;116(6):770–783. doi: 10.1093/bja/aew101.
    1. Gupta S, Mohta A, Gottumukkala V. Opioid-free anesthesia-caution for a one-size-fits-all approach. Perioper Med (Lond) 2020;9:16. doi: 10.1186/s13741-020-00147-3.
    1. Bafuma PJ, Nandi A, Weisberg M. Opiate refractory pain from an intestinal obstruction responsive to an intravenous lidocaine infusion. Am J Emerg Med. 2015;33(10):1544. doi: 10.1016/j.ajem.2015.07.027.
    1. Sousa AM, Rosado GM, Neto Jde S, Guimaraes GM, Ashmawi HA. Magnesium sulfate improves postoperative analgesia in laparoscopic gynecologic surgeries: a double-blind randomized controlled trial. J Clin Anesth. 2016;34:379–384. doi: 10.1016/j.jclinane.2016.05.006.
    1. Kim MH, Kim MS, Lee JH, Kim ST, Lee JR. Intravenously administered Lidocaine and magnesium during thyroid surgery in female patients for better quality of recovery after anesthesia. Anesth Analg. 2018;127(3):635–641. doi: 10.1213/ANE.0000000000002797.
    1. Viby-Mogensen J, Jorgensen BC, Ording H. Residual curarization in the recovery room. Anesthesiology. 1979;50(6):539–541. doi: 10.1097/00000542-197906000-00014.
    1. Carvalho H, Verdonck M, Cools W, Geerts L, Forget P, Poelaert J. Forty years of neuromuscular monitoring and postoperative residual curarisation: a meta-analysis and evaluation of confidence in network meta-analysis. Br J Anaesth. 2020;125(4):466–482. doi: 10.1016/j.bja.2020.05.063.
    1. Murphy GS, Brull SJ. Residual neuromuscular block: lessons unlearned. Part I: definitions, incidence, and adverse physiologic effects of residual neuromuscular block. Anesth Analg. 2010;111(1):120–128. doi: 10.1213/ANE.0b013e3181da832d.
    1. Debaene B, Plaud B, Dilly MP, Donati F. Residual paralysis in the PACU after a single intubating dose of nondepolarizing muscle relaxant with an intermediate duration of action. Anesthesiology. 2003;98(5):1042–1048. doi: 10.1097/00000542-200305000-00004.
    1. Beecher HK, Todd DP. A study of the deaths associated with anesthesia and surgery: based on a study of 599, 548 anesthesias in ten institutions 1948-1952, inclusive. Ann Surg. 1954;140(1):2–35. doi: 10.1097/00000658-195407000-00001.
    1. Kirmeier E, Eriksson LI, Lewald H, Jonsson Fagerlund M, Hoeft A, Hollmann M, Meistelman C, Hunter JM, Ulm K, Blobner M, et al. Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study. Lancet Respir Med. 2019;7(2):129–140. doi: 10.1016/S2213-2600(18)30294-7.
    1. Czarnetzki C, Lysakowski C, Elia N, Tramer MR. Time course of rocuronium-induced neuromuscular block after pre-treatment with magnesium sulphate: a randomised study. Acta Anaesthesiol Scand. 2010;54(3):299–306. doi: 10.1111/j.1399-6576.2009.02160.x.
    1. Kim SH, So KY, Jung KT. Effect of magnesium sulfate pretreatment on onset and recovery characteristics of cisatracurium. Korean J Anesthesiol. 2012;62(6):518–523. doi: 10.4097/kjae.2012.62.6.518.
    1. Hans GA, Bosenge B, Bonhomme VL, Brichant JF, Venneman IM, Hans PC. Intravenous magnesium re-establishes neuromuscular block after spontaneous recovery from an intubating dose of rocuronium: a randomised controlled trial. Eur J Anaesthesiol. 2012;29(2):95–99. doi: 10.1097/EJA.0b013e32834e13a6.
    1. Toft P, Kirkegaard Nielsen H, Severinsen I, Helbo-Hansen HS. Effect of epidurally administered bupivacaine on atracurium-induced neuromuscular blockade. Acta Anaesthesiol Scand. 1990;34(8):649–652. doi: 10.1111/j.1399-6576.1990.tb03165.x.
    1. Matsuo S, Rao DB, Chaudry I, Foldes FF. Interaction of muscle relaxants and local anesthetics at the neuromuscular junction. Anesth Analg. 1978;57(5):580–587. doi: 10.1213/00000539-197809000-00014.
    1. Katz RL, Gissen AJ. Effects of intravenous and intra-arterial procaine and lidocaine on neuromuscular transmission in man. Acta Anaesthesiol Scand Suppl. 1969;36:103–113. doi: 10.1111/j.1399-6576.1969.tb00482.x.
    1. Hans GA, Defresne A, Ki B, Bonhomme V, Kaba A, Legrain C, Brichant JF, Hans PC. Effect of an intravenous infusion of lidocaine on cisatracurium-induced neuromuscular block duration: a randomized-controlled trial. Acta Anaesthesiol Scand. 2010;54(10):1192–1196. doi: 10.1111/j.1399-6576.2010.02304.x.
    1. Vivancos GG, Klamt JG, Garcia LV. Effects of 2 (−)(1) of intravenous lidocaine on the latency of two different doses of rocuronium and on the hemodynamic response to orotracheal intubation. Rev Bras Anestesiol. 2011;61(1):1–12. doi: 10.1016/S0034-7094(11)70001-0.
    1. Czarnetzki C, Lysakowski C, Elia N, Tramer MR. Intravenous lidocaine has no impact on rocuronium-induced neuromuscular block. Randomised study. Acta Anaesthesiol Scand. 2012;56(4):474–481. doi: 10.1111/j.1399-6576.2011.02625.x.
    1. Fuchs-Buder T, Claudius C, Skovgaard LT, Eriksson LI, Mirakhur RK, Viby-Mogensen J. Good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents II: the Stockholm revision. Acta Anaesthesiol Scand. 2007;51(7):789–808. doi: 10.1111/j.1399-6576.2007.01352.x.
    1. Nobre F, Mion D., Jr Is the area under blood pressure curve the best parameter to evaluate 24-h ambulatory blood pressure monitoring data? Blood Press Monit. 2005;10(5):263–270. doi: 10.1097/01.mbp.0000180669.38161.6e.
    1. Singer J. A simple procedure to compute the sample size needed to compare two independent groups when the population variances are unequal. Stat Med. 2001;20(7):1089–1095. doi: 10.1002/sim.722.
    1. Brown EN, Pavone KJ, Naranjo M. Multimodal general anesthesia: theory and practice. Anesth Analg. 2018;127(5):1246–1258. doi: 10.1213/ANE.0000000000003668.
    1. Hendrickx JF, Eger EI, 2nd, Sonner JM, Shafer SL. Is synergy the rule? A review of anesthetic interactions producing hypnosis and immobility. Anesth Analg. 2008;107(2):494–506. doi: 10.1213/ane.0b013e31817b859e.
    1. Dunn LK, Durieux ME. Perioperative use of intravenous Lidocaine. Anesthesiology. 2017;126(4):729–737. doi: 10.1097/ALN.0000000000001527.
    1. Dube L, Granry JC. The therapeutic use of magnesium in anesthesiology, intensive care and emergency medicine: a review. Can J Anaesth. 2003;50(7):732–746. doi: 10.1007/BF03018719.
    1. Do SH. Magnesium: a versatile drug for anesthesiologists. Korean J Anesthesiol. 2013;65(1):4–8. doi: 10.4097/kjae.2013.65.1.4.
    1. Fuchs-Buder T, Wilder-Smith OH, Borgeat A, Tassonyi E. Interaction of magnesium sulphate with vecuronium-induced neuromuscular block. Br J Anaesth. 1995;74(4):405–409. doi: 10.1093/bja/74.4.405.
    1. Pinard AM, Donati F, Martineau R, Denault AY, Taillefer J, Carrier M. Magnesium potentiates neuromuscular blockade with cisatracurium during cardiac surgery. Can J Anaesth. 2003;50(2):172–178. doi: 10.1007/BF03017852.
    1. Rotava P, Cavalcanti IL, Barrucand L, Vane LA, Vercosa N. Effects of magnesium sulphate on the pharmacodynamics of rocuronium in patients aged 60 years and older: a randomised trial. Eur J Anaesthesiol. 2013;30(10):599–604. doi: 10.1097/EJA.0b013e328361d342.
    1. Kussman B, Shorten G, Uppington J, Comunale ME. Administration of magnesium sulphate before rocuronium: effects on speed of onset and duration of neuromuscular block. Br J Anaesth. 1997;79(1):122–124. doi: 10.1093/bja/79.1.122.
    1. James MF, Schenk PA, van der Veen BW. Priming of pancuronium with magnesium. Br J Anaesth. 1991;66(2):247–249. doi: 10.1093/bja/66.2.247.
    1. Staals LM, Driessen JJ, Van Egmond J, De Boer HD, Klimek M, Flockton EA, Snoeck MM. Train-of-four ratio recovery often precedes twitch recovery when neuromuscular block is reversed by sugammadex. Acta Anaesthesiol Scand. 2011;55(6):700–707. doi: 10.1111/j.1399-6576.2011.02448.x.
    1. Blobner M, Hunter JM, Meistelman C, Hoeft A, Hollmann MW, Kirmeier E, Lewald H, Ulm K. Use of a train-of-four ratio of 0.95 versus 0.9 for tracheal extubation: an exploratory analysis of POPULAR data. Br J Anaesth. 2020;124(1):63–72. doi: 10.1016/j.bja.2019.08.023.
    1. Capron F, Alla F, Hottier C, Meistelman C, Fuchs-Buder T. Can acceleromyography detect low levels of residual paralysis? A probability approach to detect a mechanomyographic train-of-four ratio of 0.9. Anesthesiology. 2004;100(5):1119–1124. doi: 10.1097/00000542-200405000-00013.
    1. Khan ZH, Samadi S, Ameli S, Emir Alavi C. Lidocaine as an induction agent for intracranial aneurysm surgery: a case series. Anesth Pain Med. 2016;6(1):e33250. doi: 10.5812/aapm.33250.
    1. Tremont-Lukats IW, Hutson PR, Backonja MM. A randomized, double-masked, placebo-controlled pilot trial of extended IV lidocaine infusion for relief of ongoing neuropathic pain. Clin J Pain. 2006;22(3):266–271. doi: 10.1097/01.ajp.0000169673.57062.40.
    1. Cardoso LS, Martins CR, Tardelli MA. Effects of intravenous lidocaine on the pharmacodynamics of rocuronium. Rev Bras Anestesiol. 2005;55(4):371–380. doi: 10.1590/S0034-70942005000400001.
    1. Isono S. Obesity and obstructive sleep apnoea: mechanisms for increased collapsibility of the passive pharyngeal airway. Respirology. 2012;17(1):32–42. doi: 10.1111/j.1440-1843.2011.02093.x.
    1. de Boer HD, Detriche O, Forget P. Opioid-related side effects: postoperative ileus, urinary retention, nausea and vomiting, and shivering. A review of the literature. Best Pract Res Clin Anaesthesiol. 2017;31(4):499–504. doi: 10.1016/j.bpa.2017.07.002.
    1. Angst MS, Clark JD. Opioid-induced hyperalgesia: a qualitative systematic review. Anesthesiology. 2006;104(3):570–587. doi: 10.1097/00000542-200603000-00025.
    1. Koinig H, Wallner T, Marhofer P, Andel H, Horauf K, Mayer N. Magnesium sulfate reduces intra- and postoperative analgesic requirements. Anesth Analg. 1998;87(1):206–210.
    1. Bakan M, Umutoglu T, Topuz U, Uysal H, Bayram M, Kadioglu H, Salihoglu Z. Opioid-free total intravenous anesthesia with propofol, dexmedetomidine and lidocaine infusions for laparoscopic cholecystectomy: a prospective, randomized, double-blinded study. Braz J Anesthesiol. 2015;65(3):191–199. doi: 10.1016/j.bjan.2014.05.006.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa