Effects of Intravenous Lidocaine Associated With Magnesium Sulfate on the Cisatracurium-Induced Neuromuscular Block
Condition: Neuromuscular Block
Study type: Interventional
Phase: Phase 4

Summary: 
      The magnesium sulfate and lidocaine have been increasingly used alone or in combination
      during anesthesia procedure to meet various objectives, such as reduction of pain, use of
      smaller anesthetic doses and stabilization of hemodynamic parameters.

      These medicines are often used in combination with neuromuscular blocking agents, which may
      contribute to the occurrence of residual block in some patients after anesthetic procedures.
      It was estimated that only 1-3 % of patients with residual block developing clinically
      apparent events. In a small proportion of patients, the consequences of residual blockade are
      very serious and even lethal. It is estimated that 40 % of patients with muscle paralysis
      come to the post-anesthesia care unit (PACU).

      Considering that: (a) magnesium sulfate and lidocaine are showing an increasing number of
      applications in various areas of medicine, (b) these medications stand out for their
      properties analgesic, anti-inflammatory, anti-arrhythmic, neuroprotective and capable of
      reducing the demand of anesthetics and opioids, (c) magnesium sulfate as lidocaine has been
      important part of the therapeutic arsenal to control a large number of diseases (d) the
      patient surgical surgery or potentially have benefited in particular from its effects, (and)
      these drugs have been used routinely in many medical services as well as adjuvants in
      anesthesia, (f) previous studies have shown that magnesium sulfate is able to prolong the
      duration of neuromuscular blockade by different types of muscle relaxants, with controversies
      about its effect on latency (g) the effect of lidocaine on the action of muscle relaxants in
      current literature have shown great controversy and (h) do not exist in the literature
      studies involving both drugs; the investigators aimed to investigate the effects of magnesium
      sulphate infused alone or associated with lidocaine on the neuromuscular blockade promoted by
      cisatracurium, as well as evaluate its possible hemodynamic repercussions. For this purpose
      the SM was infused in bolus, prior to tracheal intubation and continuously during the
      maintenance of general anesthesia; the Lidocaine, when associated and the Isotonic Solution
      were used in the same way and timeline as SM. As secondary objectives it has been proposed to
      evaluate if the Lidocaine with Magnesium Sulfate would be able to interfere with the
      hemodynamic stability of the patients in the study.
    

Detailed description: 
      The study was approved by the Medical Research Ethics Committee of the Hospital das Clinicas,
      of the Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil; Its Unique
      Protocol ID is 5362/2013. This study was conducted with free written informed consent from
      the study subjects.

      This report describes a prospective randomized clinical trial. The author states that the
      report includes every item in the checklist for a prospective randomized clinical trial.

      The study was registered prior to patient enrollment. Forty-eight American Society of
      Anesthesiology patient classification status ASA I and II undergoing elective surgery were
      divided into three parallel groups. The M group received MS 40 mg.kg-1 as a bolus before the
      induction of anesthesia and 20mg.kg-1h-1 via continuous i.v. infusion during the operation
      period. The ML group received identical doses of MS combined with lidocaine 3 mg.kg-1 as a
      bolus before the induction of anesthesia and 3 mg.kg-1h-1 via continuous i.v. infusion during
      the operation period. The control group was administered a equivalent volume of isotonic
      solution. Anesthesia was maintained via propofol and remifentanil infusions. After loss of
      patient consciousness and administration of the bolus infusions, a 0.15 mg.kg-1 bolus of
      cisatracurium was administered to the patient over 5 s. No additional cisatracurium
      injections were performed. The patient's neuromuscular function was assessed every 15 s by
      measuring the adductor polis with a TOF Watch SX acceleromyograph. The primary endpoint was
      the time at which spontaneous recovery of a train-of-four (TOF) ratio of 90% as achieved. The
      systolic, diastolic and mean and heart rate were recorded and annotated at various times: M1-
      when the patient arrived in the operating room; M2- immediately before induction of
      anesthesia; M3- before the infusion of the tested solutions (saline, magnesium sulphate or
      magnesium sulphate associated with lidocaine); M4- five minutes after M3 (end of infusion
      loading dose of test solutions); M5 immediately before intubation; M6- one minute after
      tracheal intubation and M7 (a through f) - every fifteen minutes until the end of the study.

      The sample size was calculated with a power of 80% to detect differences of 20% in the timing
      of clinical onset and the duration of the neuromuscular blockade (NMB). Quantitative
      variables were described as mean ± standard deviation. The normality of the distributions was
      tested for all variables in each group, using the non-parametric test of Shapiro-Wilk. When
      the variable normally distributed, we used the analysis of variance test (ANOVA) for
      comparison between groups. When differences were found between the groups, we used the Tukey
      test for multiple comparisons. When the variable is not normally distributed by applying the
      Shapiro-Wilk test, we used the Kruskal-Wallis test to compare the groups. When differences
      were found between the groups, we used the Dunn test for multiple comparisons. The critical
      level of significance was 5%.

      During the analysis of the recovery characteristics of the neuromuscular blockade, all
      parameters based on the T1 response (DUR 25% DUR 75% and DUR 95%) were normalized considering
      the final T1 value when this response did not return to baseline (VIBY-MOGENSEN et al.,
      1996).
    

Intervention name(s): Magnesium Sulfate; Lidocaine; Isotonic Solution; Cisatracurium
Intervention type(s): Drug; Drug; Drug; Drug
Other intervention name(s): Nimbex
Intervention MeSH terms: Lidocaine; Magnesium Sulfate; Cisatracurium
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Keywords: Onset; Recovery; Lidocaine; Cisatracurium; Magnesium sulfate; Isotonic solution