Neuromuscular BlockPhase 4NCT02483611

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

A Phase 4 study testing Magnesium Sulfate, Lidocaine and Isotonic Solution in people with Neuromuscular Block, run by University of Sao Paulo.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 to 60 years
Conditions the study is for: Neuromuscular Block
What is being tested?: Magnesium Sulfate, Lidocaine and Isotonic Solution
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 48 participants
Where: No sites listed yet
Study dates: Jul 2015to Sep 2015
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

ASA I or II
BMI between 18 and 29

Who cannot join

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

About this study

Official title: Effect of Intravenous Infusion of Magnesium Sulfate Associated or Not to Lidocaine On the Neuromuscular Blockade Induced by Muscle Relaxant Cistracurium

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.

Read the 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).

Conditions: Neuromuscular Block
Being tested: Magnesium Sulfate, Lidocaine, Isotonic Solution, Cisatracurium
Keywords: Onset, Recovery, Lidocaine, Cisatracurium, Magnesium sulfate, Isotonic solution

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Magnesium SulfateDrug
LidocaineDrug
Isotonic SolutionDrug
CisatracuriumDrug
Also called Nimbex

Study groups in NCT02483611
Study group	Role	What they receive
Group M	Experimental	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. Receives: Drug: Magnesium Sulfate; Drug: Cisatracurium
Group ML	Experimental	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 Receives: Drug: Magnesium Sulfate; Drug: Lidocaine; Drug: Cisatracurium
Group C	Placebo comparator	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 Receives: Drug: Isotonic Solution; Drug: Cisatracurium

What is being measured

The primary outcome is the main question the study is designed to answer.

Latency
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.
Measured: Participants were followed during the anesthetic - surgical procedure, an average of 90 minutes
Clinical Duration
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.
Measured: Participants were followed during the anesthetic - surgical procedure, an average of 90 minutes
Recovery Index
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.
Measured: Participants were followed during the anesthetic - surgical procedure, an average of 90 minutes
Final Recovery Index
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.
Measured: Participants were followed during the anesthetic - surgical procedure, an average of 90 minutes
Total Duration (Dur95%)
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.
Measured: Participants were followed during the anesthetic - surgical procedure, an average of 90 minutes
Spontaneous Recovery (T4/T1=90%)
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.
Measured: The participants were followed during the anesthetic - surgical procedure

Secondary outcomes (24)

MAP - M1 (Mean Arterial Pressure in the Moment 1)
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'.
Measured: This measure of average blood pressure was performed when the patient arrived in the operating room
MAP - M2 (Mean Arterial Pressure in the Moment 2)
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'.
Measured: This measure of average blood pressure was performed immediately before induction of anesthesia
MAP - M3 (Mean Arterial Pressure in the Moment 3)
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'.
Measured: 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)
MAP - M4 (Mean Arterial Pressure in the Moment 4)
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'.
Measured: This measure of average blood pressure was performed five minutes after M3 (in the end of the X and Y solutions infusion)
MAP - M5 (Mean Arterial Pressure in the Moment 5)
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'.
Measured: This measure of average blood pressure was performed immediately before the tracheal intubation
MAP - M6 (Mean Arterial Pressure in the Moment 6)
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'.
Measured: This measure of average blood pressure was performed one minute after the tracheal intubation
HR - M1 (Heart Rate in the Moment 1)
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'.
Measured: This measure of heart rate was performed when the patient arrived in the operating room
HR - M2 (Heart Rate in the Moment 2)
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'.
Measured: This measure of heart rate was performed immediately before induction of anesthesia
HR - M3 (Heart Rate in the Moment 3)
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'.
Measured: 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)
HR - M4 (Heart Rate in the Moment 4)
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'.
Measured: This measure of heart rate was performed five minutes after M3 (in the end of the X and Y solutions infusion)
HR - M5 (Heart Rate in the Moment 5)
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'.
Measured: This measure of heart rate was performed immediately before the tracheal intubation
HR - M6 (Heart Rate in the Moment 6)
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'.
Measured: This measure of heart rate was performed one minute after the tracheal intubation
MAP - M7a (Mean Arterial Pressure in the Moment 7a)
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'.
Measured: This measure of average blood pressure was performed 15 minutes after the traqueal intubation
MAP - M7b (Mean Arterial Pressure in the Moment 7b)
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'.
Measured: This measure of average blood pressure was performed 30 minutes after the traqueal intubation
MAP - M7c (Mean Arterial Pressure in the Moment 7c)
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'.
Measured: This measure of average blood pressure was performed 45 minutes after the traqueal intubation
MAP - M7d (Mean Arterial Pressure in the Moment 7d)
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'.
Measured: This measure of average blood pressure was performed 60 minutes after the traqueal intubation
MAP - M7e (Mean Arterial Pressure in the Moment 7e)
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'.
Measured: This measure of average blood pressure was performed 75 minutes after the traqueal intubation
MAP - M7f (Mean Arterial Pressure in the Moment 7f)
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'.
Measured: This measure of average blood pressure was performed 90 minutes after the traqueal intubation
HR - M7a (Heart Rate in the Moment 7a)
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'.
Measured: This measure of heart rate was performed 15 minutes after the traqueal intubation
HR - M7b (Heart Rate in the Moment 7b)
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'.
Measured: This measure of heart rate was performed 30 minutes after the traqueal intubation
HR - M7c (Heart Rate in the Moment 7c)
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'.
Measured: This measure of heart rate was performed 45 minutes after the traqueal intubation
HR - M7d (Heart Rate in the Moment 7d)
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'.
Measured: This measure of heart rate was performed 60 minutes after the traqueal intubation
HR - M7e (Heart Rate in the Moment 7e)
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'.
Measured: This measure of heart rate was performed 75 minutes after the traqueal intubation
HR - M7f (Heart Rate in the Moment 7f)
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'.
Measured: This measure of heart rate was performed 90 minutes after the traqueal intubation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2015Sep 2015

First posted29 Jun 2015 (estimated)
Study startJul 2015
Primary completionAug 2015
Study completionSep 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (31)Papers the sponsor has linked to this study.
Other trials for Neuromuscular BlockStudies of the same condition, open and under way.
More trials run by University of Sao PauloThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 48 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02483611
Sponsor's protocol ID: 5362/2013
Other IDs: 15541213.3.0000.5440
Status last verified: Dec 2015
First submitted: 18 Jun 2015
Last updated: 15 Jan 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Murphy GS, Brull SJ. Residual neuromuscular block: lessons unlearned. Part I: definitions, incidence, and adverse physiologic effects of residual neuromuscular block. Anesth Analg. 2010 Jul;111(1):120-8. doi: 10.1213/ANE.0b013e3181da832d. Epub 2010 May 4.
PubMed 20442260
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 May;98(5):1042-8. doi: 10.1097/00000542-200305000-00004.
PubMed 12717123
Kim MH, Oh AY, Jeon YT, Hwang JW, Do SH. A randomised controlled trial comparing rocuronium priming, magnesium pre-treatment and a combination of the two methods. Anaesthesia. 2012 Jul;67(7):748-54. doi: 10.1111/j.1365-2044.2012.07102.x. Epub 2012 Mar 15.
PubMed 22420830
Habe K, Kawasaki T, Sata T. [A case of prolongation of rocuronium neuromuscular blockade in a pregnant patient receiving magnesium]. Masui. 2014 Jul;63(7):817-9. Japanese.
PubMed 25098146
Doig GS, Simpson F. Randomization and allocation concealment: a practical guide for researchers. J Crit Care. 2005 Jun;20(2):187-91; discussion 191-3. doi: 10.1016/j.jcrc.2005.04.005.
PubMed 16139163
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 Nov;54(10):1192-6. doi: 10.1111/j.1399-6576.2010.02304.x. Epub 2010 Sep 14.
PubMed 20840515
Kim MH, Oh AY, Han SH, Kim JH, Hwang JW, Jeon YT. The effect of magnesium sulphate on intubating condition for rapid-sequence intubation: a randomized controlled trial. J Clin Anesth. 2015 Nov;27(7):595-601. doi: 10.1016/j.jclinane.2015.07.002. Epub 2015 Aug 25.
PubMed 26315876
Shahrami A, Assarzadegan F, Hatamabadi HR, Asgarzadeh M, Sarehbandi B, Asgarzadeh S. Comparison of therapeutic effects of magnesium sulfate vs. dexamethasone/metoclopramide on alleviating acute migraine headache. J Emerg Med. 2015 Jan;48(1):69-76. doi: 10.1016/j.jemermed.2014.06.055. Epub 2014 Sep 30.
PubMed 25278139
Ventham NT, Kennedy ED, Brady RR, Paterson HM, Speake D, Foo I, Fearon KC. Efficacy of Intravenous Lidocaine for Postoperative Analgesia Following Laparoscopic Surgery: A Meta-Analysis. World J Surg. 2015 Sep;39(9):2220-34. doi: 10.1007/s00268-015-3105-6.
PubMed 26044546
Govindarajan R, Shah A, Reddy VS, Parithivel V, Ravikumar S, Livingstone D. Improving the functionality of intra-operative nerve monitoring during thyroid surgery: is lidocaine an option? J Clin Med Res. 2015 Apr;7(4):282-5. doi: 10.14740/jocmr2025w. Epub 2015 Feb 9.
PubMed 25699129
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 Mar;54(3):299-306. doi: 10.1111/j.1399-6576.2009.02160.x. Epub 2009 Nov 16.
PubMed 19919585
Czarnetzki C, Lysakowski C, Elia N, Tramer MR. Intravenous lidocaine has no impact on rocuronium-induced neuromuscular block. Randomised study. Acta Anaesthesiol Scand. 2012 Apr;56(4):474-81. doi: 10.1111/j.1399-6576.2011.02625.x. Epub 2012 Jan 19.
PubMed 22260297
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 Feb;29(2):95-9. doi: 10.1097/EJA.0b013e32834e13a6.
PubMed 22183158
Kim SH, So KY, Jung KT. Effect of magnesium sulfate pretreatment on onset and recovery characteristics of cisatracurium. Korean J Anesthesiol. 2012 Jun;62(6):518-23. doi: 10.4097/kjae.2012.62.6.518. Epub 2012 Jun 19.
PubMed 22778886
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 Jul;79(1):122-4. doi: 10.1093/bja/79.1.122.
PubMed 9301400

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Active, not recruiting
Efficacy of Laparoscopic-Assisted TAP Block in Laparoscopic Appendectomy
Appendectomy, Laparoscopic, Blockades Neuromuscular
Not yet recruitingObservational study
Diaphragm Ultrasound and Neuromuscular Monitoring for Predicting Early Respiratory Events After Extubation
Residual Neuromuscular Blockade, Diaphragm Dysfunction
RecruitingObservational study
The Association Between Residual Neuromuscular Block Risk Prediction Score and the Train-of-Four Ratio
Muscle Relaxants
Not yet recruitingObservational study
Sugammadex Timing and Recovery Profile in Pediatric Adenotonsillectomy
Neuromuscular Blockade, Delayed Emergence From Anesthesia
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders

All Neuromuscular Block trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effect of Intravenous Infusion of Magnesium Sulfate Associated or Not to Lidocaine On the Neuromuscular Blockade Induced by Muscle Relaxant Cistracurium
ClinicalTrials.gov ID: NCT02483611
Acronym / sponsor ID: 5362/2013
Conditions: Neuromuscular Block
Keywords: Onset, Recovery, Lidocaine, Cisatracurium, Magnesium sulfate, Isotonic solution
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 48 participants (actual)
Lead sponsor: University of Sao PauloUniversity, hospital or other
Study start: Jul 2015
Primary completion: Aug 2015 (actual)
Study completion: Sep 2015 (actual)
First posted: 29 Jun 2015 (estimated)
Results: Posted 15 Jan 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Study design

Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 3

Arm	Type	Receives
Group M	Experimental	Drug: Magnesium Sulfate, Drug: CisatracuriumMagnesium 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.
Group ML	Experimental	Drug: Magnesium Sulfate, Drug: Lidocaine, Drug: CisatracuriumMagnesium 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
Group C	Placebo comparator	Drug: Isotonic Solution, Drug: CisatracuriumIsotonic 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

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (2 listed)

ASA I or II
BMI between 18 and 29

Key exclusion criteria (4 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Magnesium Sulfate	Drug	Group M, Group ML
Lidocaine	Drug	Group ML
Isotonic Solution	Drug	Group C
CisatracuriumAlso: Nimbex	Drug	Group C, Group M, Group ML

Primary outcome

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.
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.
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.
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.
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.
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.

24 secondary outcomes

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
MAP - M2 (Mean Arterial Pressure in the Moment 2)
Time frame: This measure of average blood pressure was performed immediately before induction of anesthesia
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)
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)
MAP - M5 (Mean Arterial Pressure in the Moment 5)
Time frame: This measure of average blood pressure was performed immediately before the tracheal intubation
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
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
HR - M2 (Heart Rate in the Moment 2)
Time frame: This measure of heart rate was performed immediately before induction of anesthesia
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)
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)
HR - M5 (Heart Rate in the Moment 5)
Time frame: This measure of heart rate was performed immediately before the tracheal intubation
HR - M6 (Heart Rate in the Moment 6)
Time frame: This measure of heart rate was performed one minute after the tracheal intubation
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
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
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
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
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
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
HR - M7a (Heart Rate in the Moment 7a)
Time frame: This measure of heart rate was performed 15 minutes after the traqueal intubation
HR - M7b (Heart Rate in the Moment 7b)
Time frame: This measure of heart rate was performed 30 minutes after the traqueal intubation
HR - M7c (Heart Rate in the Moment 7c)
Time frame: This measure of heart rate was performed 45 minutes after the traqueal intubation
HR - M7d (Heart Rate in the Moment 7d)
Time frame: This measure of heart rate was performed 60 minutes after the traqueal intubation
HR - M7e (Heart Rate in the Moment 7e)
Time frame: This measure of heart rate was performed 75 minutes after the traqueal intubation
HR - M7f (Heart Rate in the Moment 7f)
Time frame: This measure of heart rate was performed 90 minutes after the traqueal intubation

Results and safety

Results posted to the registry on 15 Jan 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group M (Magnesium Sulfate)	16	16
Group ML (Magnesium Sulfate Plus Lidocaine)	16	16
Group C (Control Group - Isotonic Solution)	16	15

Primary outcome: Latency

Time frame: Participants were followed during the anesthetic - surgical procedure, an average of 90 minutes. Mean (Standard Deviation). Unit: seconds

Measure	Group M n = 16	Group ML n = 16	Group C n = 15
Value	139.70 (47.92)	151.30 (47.97)	147.80 (29.75)

Group M: Mean Difference (Final Values): 149 (95% CI 88 to 235), p = 0.9651, ANOVA
Group ML: Mean Difference (Final Values): 145.30 (95% CI 78 to 244), p = 0.9651, ANOVA
Group C: Mean Difference (Final Values): 147.80 (95% CI 105 to 200), p = 0.9651, ANOVA

Population analysed: 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 NMB. This pharmacodynamic variable was compared between the groups by analysis of variance (Anova one way) and Tukey post-hoc test (p value \< 0.05)

Primary outcome: Clinical Duration

Time frame: Participants were followed during the anesthetic - surgical procedure, an average of 90 minutes. Median (Inter-Quartile Range). Unit: minutes

Measure	Group M n = 16	Group ML n = 16	Group C n = 15
Value	82.68 (76.83 to 91.19)	86.33 (82.65 to 88.19)	64.8 (57.05 to 70.23)

Group M: Median Difference (Final Values): 82.68 (95% CI 72.62 to 99.27), p <0.0001, Kruskal-Wallis
Group ML: Median Difference (Final Values): 86.33 (95% CI 71.78 to 140.60), p <0.0001, Kruskal-Wallis
Group C: Median Difference (Final Values): 64.80 (95% CI 40.50 to 92.90), p <0.0001, Kruskal-Wallis

Population analysed: 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 NMB. This pharmacodynamic variable was compared between the groups by Kruskal-Wallis test. When differences were found between the groups, we used the Dunn test for multiple comparisons (p value \< 0.05)

Primary outcome: Recovery Index

Time frame: Participants were followed during the anesthetic - surgical procedure, an average of 90 minutes. Mean (Standard Deviation). Unit: minutes

Measure	Group M n = 16	Group ML n = 16	Group C n = 15
Value	20.08 (6.49)	20.26 (7.69)	14.53 (1.52)

Group M: Mean Difference (Final Values): 20.08 (95% CI 12.00 to 32.25), p = 0.0015, ANOVA
Group ML: Mean Difference (Final Values): 20.26 (95% CI 10.50 to 39.83), p = 0.0015, ANOVA
Group C: Mean Difference (Final Values): 14.53 (95% CI 11.00 to 16.50), p = 0.0015, ANOVA

Primary outcome: Final Recovery Index

Time frame: Participants were followed during the anesthetic - surgical procedure, an average of 90 minutes. Mean (Standard Deviation). Unit: minutes

Measure	Group M n = 16	Group ML n = 16	Group C n = 15
Value	27.97 (6.77)	33.81 (10.97)	21.51 (3.28)

Group M: Mean Difference (Final Values): 27.97 (95% CI 19.50 to 41.50), p = 0.0003, ANOVA
Group ML: Mean Difference (Final Values): 33.81 (95% CI 18.50 to 49.50), p = 0.0003, ANOVA
Group C: Mean Difference (Final Values): 21.51 (95% CI 17.50 to 30.05), p = 0.0003, ANOVA

24 secondary outcomes are reported in the full results.

Adverse events

Time frame: The adverse event data were collected during the intra and posopertive period.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group M	0 of 16 (0%)	0 of 16 (0%)	Not reported
Group ML	0 of 16 (0%)	0 of 16 (0%)	Not reported
Group C	0 of 15 (0%)	0 of 15 (0%)	Not reported

Limitations and caveats (from the sponsor): -It was not possible to measure Magnesium sulfate and Lidocaine levels

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 20442260Murphy GS, Brull SJ. Residual neuromuscular block: lessons unlearned. Part I: definitions, incidence, and adverse physiologic effects of residual neuromuscular block. Anesth Analg. 2010 Jul;111(1):120-8. doi: 10.1213/ANE.0b013e3181da832d. Epub 2010 May 4.
Background: PubMed 12717123Debaene 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 May;98(5):1042-8. doi: 10.1097/00000542-200305000-00004.
Background: PubMed 22420830Kim MH, Oh AY, Jeon YT, Hwang JW, Do SH. A randomised controlled trial comparing rocuronium priming, magnesium pre-treatment and a combination of the two methods. Anaesthesia. 2012 Jul;67(7):748-54. doi: 10.1111/j.1365-2044.2012.07102.x. Epub 2012 Mar 15.
Background: PubMed 25098146Habe K, Kawasaki T, Sata T. [A case of prolongation of rocuronium neuromuscular blockade in a pregnant patient receiving magnesium]. Masui. 2014 Jul;63(7):817-9. Japanese.
Background: PubMed 16139163Doig GS, Simpson F. Randomization and allocation concealment: a practical guide for researchers. J Crit Care. 2005 Jun;20(2):187-91; discussion 191-3. doi: 10.1016/j.jcrc.2005.04.005.
Background: PubMed 20840515Hans 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 Nov;54(10):1192-6. doi: 10.1111/j.1399-6576.2010.02304.x. Epub 2010 Sep 14.
Background: PubMed 26315876Kim MH, Oh AY, Han SH, Kim JH, Hwang JW, Jeon YT. The effect of magnesium sulphate on intubating condition for rapid-sequence intubation: a randomized controlled trial. J Clin Anesth. 2015 Nov;27(7):595-601. doi: 10.1016/j.jclinane.2015.07.002. Epub 2015 Aug 25.
Background: PubMed 25278139Shahrami A, Assarzadegan F, Hatamabadi HR, Asgarzadeh M, Sarehbandi B, Asgarzadeh S. Comparison of therapeutic effects of magnesium sulfate vs. dexamethasone/metoclopramide on alleviating acute migraine headache. J Emerg Med. 2015 Jan;48(1):69-76. doi: 10.1016/j.jemermed.2014.06.055. Epub 2014 Sep 30.
Background: PubMed 26044546Ventham NT, Kennedy ED, Brady RR, Paterson HM, Speake D, Foo I, Fearon KC. Efficacy of Intravenous Lidocaine for Postoperative Analgesia Following Laparoscopic Surgery: A Meta-Analysis. World J Surg. 2015 Sep;39(9):2220-34. doi: 10.1007/s00268-015-3105-6.
Background: PubMed 25699129Govindarajan R, Shah A, Reddy VS, Parithivel V, Ravikumar S, Livingstone D. Improving the functionality of intra-operative nerve monitoring during thyroid surgery: is lidocaine an option? J Clin Med Res. 2015 Apr;7(4):282-5. doi: 10.14740/jocmr2025w. Epub 2015 Feb 9.
Results publication: PubMed 19919585Czarnetzki 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 Mar;54(3):299-306. doi: 10.1111/j.1399-6576.2009.02160.x. Epub 2009 Nov 16.
Results publication: PubMed 22260297Czarnetzki C, Lysakowski C, Elia N, Tramer MR. Intravenous lidocaine has no impact on rocuronium-induced neuromuscular block. Randomised study. Acta Anaesthesiol Scand. 2012 Apr;56(4):474-81. doi: 10.1111/j.1399-6576.2011.02625.x. Epub 2012 Jan 19.

Related trials for Neuromuscular Block

Active, not recruiting
Efficacy of Laparoscopic-Assisted TAP Block in Laparoscopic Appendectomy
Appendectomy, Laparoscopic, Blockades Neuromuscular
Not yet recruitingObservational study
Diaphragm Ultrasound and Neuromuscular Monitoring for Predicting Early Respiratory Events After Extubation
Residual Neuromuscular Blockade, Diaphragm Dysfunction
RecruitingObservational study
The Association Between Residual Neuromuscular Block Risk Prediction Score and the Train-of-Four Ratio
Muscle Relaxants
Not yet recruitingObservational study
Sugammadex Timing and Recovery Profile in Pediatric Adenotonsillectomy
Neuromuscular Blockade, Delayed Emergence From Anesthesia
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Magnesium Sulfate, Lidocaine and Isotonic Solution in people with Neuromuscular Block, run by University of Sao Paulo.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Jan 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Latency (time frame: Participants were followed during the anesthetic - surgical procedure, an average of 90 minutes). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02483611, which also lists 31 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2016.