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Effects of Intravenous Lidocaine Associated With Magnesium Sulfate on the Cisatracurium-Induced Neuromuscular Block

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ClinicalTrials.gov Identifier: NCT02483611
Recruitment Status : Completed
First Posted : June 29, 2015
Results First Posted : January 15, 2016
Last Update Posted : January 15, 2016
Sponsor:
Information provided by (Responsible Party):
Waynice N.P. Garcia, University of Sao Paulo

Brief 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.


Condition or disease Intervention/treatment Phase
Neuromuscular Block Drug: Magnesium Sulfate Drug: Lidocaine Drug: Isotonic Solution Drug: Cisatracurium Phase 4

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).


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Official Title: Effect of Intravenous Infusion of Magnesium Sulfate Associated or Not to Lidocaine On the Neuromuscular Blockade Induced by Muscle Relaxant Cistracurium
Study Start Date : July 2015
Actual Primary Completion Date : August 2015
Actual Study Completion Date : September 2015


Arm Intervention/treatment
Experimental: Group M

Magnesium Sulfate. In this group, the patients received magnesium sulfate 40 mg/Kg as a bolus and 20 mg/kg/h by continuous IV infusion during surgery.

After the bolus of magnesium sulfate, 0.15 mg/kg of cisatracurium was infused over 5 seconds.

Drug: Magnesium Sulfate
Drug: Cisatracurium
Other Name: Nimbex

Experimental: Group ML

Magnesium Sulfate plus Lidocaine. In this group, the patients received 40 mg/kg of Magnesium Sulfate plus 3 mg kg-1 lidocaine as a bolus and 20 mg/kg/h and 3 mg/kg/h, respectively, by infusion continuously during the surgery.

After the bolus of magnesium sulfate and lidocaine, 0.15 mg/kg of cisatracurium was infused over 5 seconds

Drug: Magnesium Sulfate
Drug: Lidocaine
Drug: Cisatracurium
Other Name: Nimbex

Placebo Comparator: Group C

Isotonic Solution. In this group, the patients received the volume of isotonic solution equivalent to the volume of solution infused into experimental groups.

After the bolus of the isotonic solution , 0.15 mg/kg of cisatracurium was infused over 5 seconds

Drug: Isotonic Solution
Drug: Cisatracurium
Other Name: Nimbex




Primary Outcome Measures :
  1. Latency [ Time Frame: Participants were followed during the anesthetic - surgical procedure, an average of 90 minutes ]

    The latency is computed as the elapsed time to reduce the response of T1 to 5% of the initial contraction force after the infusion of cisatracurium.

    This outcome meansure was presented in seconds.


  2. Clinical Duration [ Time Frame: Participants were followed during the anesthetic - surgical procedure, an average of 90 minutes ]

    The clinical duration is the elapsed time for T1 recovery = 25% (Dur25%) of the original value of T1 after the infusion of cisatracurium.

    This outcome meansure was presented in minutes.


  3. Recovery Index [ Time Frame: Participants were followed during the anesthetic - surgical procedure, an average of 90 minutes ]

    The recovery index is the elapsed time between the T1 recovery =25% (Dur25%) and T1 =75% (Dur75%) after the infusion of cisatracurium.

    This outcome meansure was presented in minutes.


  4. Final Recovery Index [ Time Frame: Participants were followed during the anesthetic - surgical procedure, an average of 90 minutes ]

    The final recovery index is the elapsed time between the T1 recovery = 25% (Dur25%) and T4 / T1 = 80% (TOF = 80%) after the infusion of cisatracurium.

    This outcome measure was presented in minutes.


  5. Total Duration (Dur95%) [ Time Frame: Participants were followed during the anesthetic - surgical procedure, an average of 90 minutes ]

    The total duration is the elapsed time for T1 recovery of the response to reach 95% of the initial after the infusion of cisatracurium.

    This outcome measure was presented in minutes.


  6. Spontaneous Recovery (T4/T1=90%) [ Time Frame: The participants were followed during the anesthetic - surgical procedure ]

    Spontaneous recovery is the elapsed time for the recovery of the TOF (T4 / T1) response to 90% of the original after infusion of cisatracurium.

    This outcome measure was presented in minutes.



Secondary Outcome Measures :
  1. MAP - M1 (Mean Arterial Pressure in the Moment 1) [ Time Frame: This measure of average blood pressure was performed when the patient arrived in the operating room ]
    In the operating room, patients were cardiovascular, respiratory and body temperature monitored through the Dixtal 2020. The mean blood pressure was recorded and annotated at various times such as in the arrival of the patient in the operating room. This time point was named as moment '1'.

  2. MAP - M2 (Mean Arterial Pressure in the Moment 2) [ Time Frame: This measure of average blood pressure was performed immediately before induction of anesthesia ]
    In the operating room, patients were cardiovascular, respiratory and body temperature monitored through the Dixtal 2020. The mean blood pressure was recorded and annotated at various times such as in the moment immediately before the anesthesia induction. This time point was named as moment '2'.

  3. MAP - M3 (Mean Arterial Pressure in the Moment 3) [ Time Frame: This measure of average blood pressure was performed immediately before the start of the infusion of the solution X (magnesium sulfate or isotonic solution) and Y solution (lidocaine or isotonic solution) ]
    In the operating room, patients were cardiovascular, respiratory and body temperature monitored through the Dixtal 2020. The mean blood pressure was recorded and annotated at various times such as immediately before the start of the infusion of the solution X (magnesium sulfate or isotonic solution) and Y solution (lidocaine or isotonic solution). This time point was named as moment '3'.

  4. MAP - M4 (Mean Arterial Pressure in the Moment 4) [ Time Frame: This measure of average blood pressure was performed five minutes after M3 (in the end of the X and Y solutions infusion) ]
    In the operating room, patients were cardiovascular, respiratory and body temperature monitored through the Dixtal 2020. The mean blood pressure was recorded and annotated at various times such as in the end of the study solutions infusion.This time point was named as moment '4'.

  5. MAP - M5 (Mean Arterial Pressure in the Moment 5) [ Time Frame: This measure of average blood pressure was performed immediately before the tracheal intubation ]
    In the operating room, patients were cardiovascular, respiratory and body temperature monitored through the Dixtal 2020. The mean blood pressure was recorded and annotated at various times such as immediately before the tracheal intubation. This time point was named as moment '5'.

  6. MAP - M6 (Mean Arterial Pressure in the Moment 6) [ Time Frame: This measure of average blood pressure was performed one minute after the tracheal intubation ]
    In the operating room, patients were cardiovascular, respiratory and body temperature monitored through the Dixtal 2020. The mean blood pressure was recorded and annotated at various times such as one minute after the tracheal intubation. This time point was named as moment '6'.

  7. HR - M1 (Heart Rate in the Moment 1) [ Time Frame: This measure of heart rate was performed when the patient arrived in the operating room ]
    In the operating room, patients were cardiovascular, respiratory and body temperature monitored through the Dixtal 2020. The measure of heart rate was recorded and annotated at various times such as in the arrival of the patient in the operating room. This time point was named as moment '1'.

  8. HR - M2 (Heart Rate in the Moment 2) [ Time Frame: This measure of heart rate was performed immediately before induction of anesthesia ]
    In the operating room, patients were cardiovascular, respiratory and body temperature monitored through the Dixtal 2020. The heart rate was recorded and annotated at various times such as in the moment immediately before the anesthesia induction. This time point was named as moment '2'.

  9. HR - M3 (Heart Rate in the Moment 3) [ Time Frame: This measure of heart rate was performed immediately before the start of the infusion of the solution X (magnesium sulfate or isotonic solution) and Y solution (lidocaine or isotonic solution) ]
    In the operating room, patients were cardiovascular, respiratory and body temperature monitored through the Dixtal 2020. The heart rate was recorded and annotated at various times such as immediately before the start of the infusion of the solution X (magnesium sulfate or isotonic solution) and Y solution (lidocaine or isotonic solution). This time point was named as moment '3'.

  10. HR - M4 (Heart Rate in the Moment 4) [ Time Frame: This measure of heart rate was performed five minutes after M3 (in the end of the X and Y solutions infusion) ]
    In the operating room, patients were cardiovascular, respiratory and body temperature monitored through the Dixtal 2020. The heart rate was recorded and annotated at various times such as in the end of the study solutions infusion. This time point was named as moment '4'.

  11. HR - M5 (Heart Rate in the Moment 5) [ Time Frame: This measure of heart rate was performed immediately before the tracheal intubation ]
    In the operating room, patients were cardiovascular, respiratory and body temperature monitored through the Dixtal 2020. The heart rate was recorded and annotated at various times such as immediately before the tracheal intubation. This time point was named as moment '5'.

  12. HR - M6 (Heart Rate in the Moment 6) [ Time Frame: This measure of heart rate was performed one minute after the tracheal intubation ]
    In the operating room, patients were cardiovascular, respiratory and body temperature monitored through the Dixtal 2020. The heart rate was recorded and annotated at various times such as one minute after the tracheal intubation. This time point was named as moment '6'.

  13. MAP - M7a (Mean Arterial Pressure in the Moment 7a) [ Time Frame: This measure of average blood pressure was performed 15 minutes after the traqueal intubation ]
    In the operating room, patients were cardiovascular, respiratory and body temperature monitored through the Dixtal 2020. The mean blood pressure was recorded and annotated at various times such as 15 minutes after the traqueal intubation. This time point was named as moment '7a'.

  14. MAP - M7b (Mean Arterial Pressure in the Moment 7b) [ Time Frame: This measure of average blood pressure was performed 30 minutes after the traqueal intubation ]
    In the operating room, patients were cardiovascular, respiratory and body temperature monitored through the Dixtal 2020. The mean blood pressure was recorded and annotated at various times such as 30 minutes after the traqueal intubation. This time point was named as moment '7b'.

  15. MAP - M7c (Mean Arterial Pressure in the Moment 7c) [ Time Frame: This measure of average blood pressure was performed 45 minutes after the traqueal intubation ]
    In the operating room, patients were cardiovascular, respiratory and body temperature monitored through the Dixtal 2020. The mean blood pressure was recorded and annotated at various times such as 45 minutes after the traqueal intubation. This time point was named as moment '7c'.

  16. MAP - M7d (Mean Arterial Pressure in the Moment 7d) [ Time Frame: This measure of average blood pressure was performed 60 minutes after the traqueal intubation ]
    In the operating room, patients were cardiovascular, respiratory and body temperature monitored through the Dixtal 2020. The mean blood pressure was recorded and annotated at various times such as 60 minutes after the traqueal intubation. This time point was named as moment '7d'.

  17. MAP - M7e (Mean Arterial Pressure in the Moment 7e) [ Time Frame: This measure of average blood pressure was performed 75 minutes after the traqueal intubation ]
    In the operating room, patients were cardiovascular, respiratory and body temperature monitored through the Dixtal 2020. The mean blood pressure was recorded and annotated at various times such as 75 minutes after the traqueal intubation. This time point was named as moment '7e'.

  18. MAP - M7f (Mean Arterial Pressure in the Moment 7f) [ Time Frame: This measure of average blood pressure was performed 90 minutes after the traqueal intubation ]
    In the operating room, patients were cardiovascular, respiratory and body temperature monitored through the Dixtal 2020. The mean blood pressure was recorded and annotated at various times such as 90 minutes after the traqueal intubation. This time point was named as moment '7f'.

  19. HR - M7a (Heart Rate in the Moment 7a) [ Time Frame: This measure of heart rate was performed 15 minutes after the traqueal intubation ]
    In the operating room, patients were cardiovascular, respiratory and body temperature monitored through the Dixtal 2020. The heart rate was recorded and annotated at various times such as 15 minutes after the traqueal intubation.This time point was named as moment '7a'.

  20. HR - M7b (Heart Rate in the Moment 7b) [ Time Frame: This measure of heart rate was performed 30 minutes after the traqueal intubation ]
    In the operating room, patients were cardiovascular, respiratory and body temperature monitored through the Dixtal 2020. The heart rate was recorded and annotated at various times such as 30 minutes after the traqueal intubation. This time point was named as moment '7b'.

  21. HR - M7c (Heart Rate in the Moment 7c) [ Time Frame: This measure of heart rate was performed 45 minutes after the traqueal intubation ]
    In the operating room, patients were cardiovascular, respiratory and body temperature monitored through the Dixtal 2020. The heart rate was recorded and annotated at various times such as 45 minutes after the traqueal intubation. This time point was named as moment '7c'.

  22. HR - M7d (Heart Rate in the Moment 7d) [ Time Frame: This measure of heart rate was performed 60 minutes after the traqueal intubation ]
    In the operating room, patients were cardiovascular, respiratory and body temperature monitored through the Dixtal 2020. The heart rate was recorded and annotated at various times such as 60 minutes after the traqueal intubation. This time point was named as moment '7d'.

  23. HR - M7e (Heart Rate in the Moment 7e) [ Time Frame: This measure of heart rate was performed 75 minutes after the traqueal intubation ]
    In the operating room, patients were cardiovascular, respiratory and body temperature monitored through the Dixtal 2020. The heart rate was recorded and annotated at various times such as 75 minutes after the traqueal intubation. This time point was named as moment '7e'.

  24. HR - M7f (Heart Rate in the Moment 7f) [ Time Frame: This measure of heart rate was performed 90 minutes after the traqueal intubation ]
    In the operating room, patients were cardiovascular, respiratory and body temperature monitored through the Dixtal 2020. The heart rate was recorded and annotated at various times such as 90 minutes after the traqueal intubation. This time point was named as moment '7f'.



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Layout table for eligibility information
Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Before the recruitment of patients, the study was approved by Brazil Platform (a national and unified basis of research involving human subjects records) and published by the ClinicalTrials.gov

Inclusion Criteria:

  • ASA I or II
  • BMI between 18 and 29

Exclusion Criteria:

  • Use of medications that could affect the neuromuscular blockade such as calcium channel inhibitors, anticonvulsants and lithium carbonate
  • Presence of neuromuscular, renal or hepatic dysfunction.
  • Hypermetabolic or hypometabolic states such as fever, infection, and hyperthyroidism or hypothyroidism
  • Acid-base disorder, congestive heart failure or conductive heart problems, and those who were being treated for cardiac arrhythmias

Publications of Results:

Other Publications:

Layout table for additonal information
Responsible Party: Waynice N.P. Garcia, M.D., Ph.D, University of Sao Paulo
ClinicalTrials.gov Identifier: NCT02483611     History of Changes
Other Study ID Numbers: 5362/2013
15541213.3.0000.5440 ( Registry Identifier: [Plataforma Brasil] )
First Posted: June 29, 2015    Key Record Dates
Results First Posted: January 15, 2016
Last Update Posted: January 15, 2016
Last Verified: December 2015
Keywords provided by Waynice N.P. Garcia, University of Sao Paulo:
Onset
Recovery
Lidocaine
Cisatracurium
Magnesium sulfate
Isotonic solution
Additional relevant MeSH terms:
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Lidocaine
Magnesium Sulfate
Pharmaceutical Solutions
Cisatracurium
Atracurium
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Anti-Arrhythmia Agents
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Analgesics
Anticonvulsants
Calcium Channel Blockers
Calcium-Regulating Hormones and Agents
Tocolytic Agents
Reproductive Control Agents
Neuromuscular Blocking Agents
Neuromuscular Agents
Neuromuscular Nondepolarizing Agents
Nicotinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents