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Combination of Magnesium and Lidocaine for the Pretreatment of Pain That is Caused by the Injection of Propofol

The Evaluation of the Combination of Magnesium and Lidocaine for the Pretreatment of Pain That is Caused by the Injection of Propofol.

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01342510
Enrollment
200
Registered
2011-04-27
Start date
2011-04-30
Completion date
2012-04-30
Last updated
2019-05-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

General Anesthesia, Intravenous Anesthesia

Keywords

Intravenous Anesthesia, General Anesthesia

Brief summary

Since the introduction of propofol into routine anesthesia practice, the phenomena of pain on injection has plagued anesthesia providers. Propofol, an unstable phenol, triggers the release of bradykinin on injection. This release causes a painful burning sensation in the patient at the site of injection. Anesthesia providers have attempted a large number of remedies to prevent this pain on injection. Previously explored ideas include injecting propofol into larger veins, warming of the hand with hot packs, and intravenous pretreatment with numerous other medications. Currently, pretreatment with lidocaine is commonly administered to prevent propofol injection pain. No studies to date have looked at the combination of lidocaine and magnesium in a single syringe for the pretreatment of pain on injection caused by propofol. In addition, the administration protocols that have been studied thus far do not mirror clinical practice at the University of Wisconsin. The investigators propose studying the use of magnesium and lidocaine in a single syringe for pretreatment of propofol related pain on injection.

Detailed description

This study will involve little if any change from the typical induction of general anesthesia. Considering that lidocaine is routinely used for the induction of anesthesia, and that some anesthesia staff also inject magnesium prior to propofol, there will be little variation in the induction of anesthesia. Patients will be randomly assigned (by microsoft excel program providing a random number 1-4) to one of four groups: 1. Lidocaine 50 mg in a 10 cc syringe 2. Magnesium sulfate 0.25 g (2 mOsmol) in a 10 cc syringe 3. 0.9% saline in a 10 cc syringe 4. Lidocaine 50 mg and 0.25 g (2 mOsmol) magnesium sulfate in a 10 cc syringe Study drugs will be prepared in identical syringes by the Pharmaceutical Research Center (PRC). Study personnel will receive a syringe labeled with the study number as well as a data collection sheet labeled with the study number. A 20 gauge angiocatheter will be inserted into the dorsum of the hand for IV fluids and medication administration. Subjects will be given preoperative 1-2 mg intravenous midazolam for sedation when the subject is en route to the operating room as is typically done at the discretion of the anesthesia provider caring for the patient. After instituting standard monitors and providing preoxygenation, the study drug will be injected. Twenty seconds later, 50 mg of propofol will be injected. Ten seconds after infusion of propofol, the subjects will then be asked a standard question about pain on injection Are you having pain at your IV site?. Any behavioral signs such as facial grimacing, arm withdrawal, or tears will be noted. Pain will be assessed using a four point scale: 0=no pain, 1=mild pain (pain reported only in response to questioning and without behavioral signs), 2=moderate pain (pain reported in response to questioning and accompanied by a behavioral sign, or pain reported spontaneously without questioning), 3=severe pain (strong vocal response or response accompanied by facial grimacing, arm withdrawal, or tears). Study key personnel will do these pain assessments; the behavioral signs and self-reporting of pain will be recorded separate from one another. The induction of anesthesia will then by completed with the appropriate amount of propofol. Formally assessing pain following injection is not something that is standard care but all patients are currently warned prior to injection that they may experience some warmth or burning at the site of their intravenous line.

Interventions

DRUGMagnesium Sulfate

We propose studying Lidocaine 50 mg in a 10 cc syringe, Magnesium sulfate 0.25 g (2 mOsmol) in a 10 cc syringe, 0.9% saline in a 10 cc syringe, Lidocaine 50 mg and 0.25 g (2 mOsmol) magnesium sulfate in a 10 cc syringe for pretreatment of propofol related pain on injection.

DRUGLidocaine

We propose studying Lidocaine 50 mg in a 10 cc syringe, Magnesium sulfate 0.25 g (2 mOsmol) in a 10 cc syringe, 0.9% saline in a 10 cc syringe, Lidocaine 50 mg and 0.25 g (2 mOsmol) magnesium sulfate in a 10 cc syringe for pretreatment of propofol related pain on injection.

DRUGControl

We propose studying Lidocaine 50 mg in a 10 cc syringe, Magnesium sulfate 0.25 g (2 mOsmol) in a 10 cc syringe, 0.9% saline in a 10 cc syringe, Lidocaine 50 mg and 0.25 g (2 mOsmol) magnesium sulfate in a 10 cc syringe for pretreatment of propofol related pain on injection.

DRUGLidocaine/Magnesium

We propose studying Lidocaine 50 mg in a 10 cc syringe, Magnesium sulfate 0.25 g (2 mOsmol) in a 10 cc syringe, 0.9% saline in a 10 cc syringe, Lidocaine 50 mg and 0.25 g (2 mOsmol) magnesium sulfate in a 10 cc syringe for pretreatment of propofol related pain on injection.

Sponsors

University of Wisconsin, Madison
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes

Inclusion criteria

* All adults American Society of Anesthesiologists (ASA) physical status 1 and 2 patients selected for general anesthesia.

Exclusion criteria

* age \< 18 years * allergy to local anesthetics * end stage renal disease * pregnancy * prisoners * patients requiring a rapid sequence induction * refusal to participate and patients already participating in another study

Design outcomes

Primary

MeasureTime frameDescription
Percentage of Participants Reporting Pain With Injection of PropofolApproximately 10 seconds following administration of propofol.Following injection of the study drug, 50 mg of propofol will be injected. Ten seconds after propofol, subjects will be asked a standard question about pain. Behavioral signs will be noted. Pain will be assessed using a four point scale: 0=no pain, 1=mild pain (pain reported only in response to questioning and without behavioral signs), 2=moderate pain (pain reported in response to questioning and a behavioral sign, or pain reported without questioning), 3=severe pain (strong vocal response or behavioral response).
Number of Patients With Pain Associated With Injection of Propofol.< 1 minute.Ten seconds following injection of propofol, subjects were asked Are you having pain at your IV site? Any behavioral signs were noted. Injection pain was assessed using the following four point scale: 0 = no pain; 1 = mild pain (pain reported only in response to questioning and without behavioral signs); 2 = moderate pain (pain reported in response to questioning and accompanied by a behavioral sign, or pain reported spontaneously without questioning); and 3 = severe pain (strong vocal response or response accompanied by facial grimacing, arm withdrawal, or tears).

Countries

United States

Participant flow

Recruitment details

Participants were recruited between 6/2011 and 10/2011.

Pre-assignment details

200 participants were consented. The participants were distributed between the groups as follows, 39 participants in the control group, 38 in the lidocaine group, 44 in the magnesium group, and 37 in the magnesium/lidocaine group. Participants did not receive study drug if ASA score or peripheral IV inserted was not a 20 gauge.

Participants by arm

ArmCount
Lidocaine
Lidocaine 50 mg in a 10 cc syringe
38
Magnesium
Magnesium sulfate 0.25 g (2 mOsmol) in a 10 cc syringe
44
Lidocaine/Magnesium
Lidocaine 50 mg and 0.25 g (2 mOsmol) magnesium sulfate in a 10 cc syringe
37
Control
0.9% saline in a 10 cc syringe
39
Total158

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003
Overall StudyProtocol Violation1261311

Baseline characteristics

CharacteristicMagnesiumLidocaine/MagnesiumLidocaineControlTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
3 Participants4 Participants3 Participants8 Participants18 Participants
Age, Categorical
Between 18 and 65 years
41 Participants33 Participants35 Participants31 Participants140 Participants
Age, Continuous44.4 years
STANDARD_DEVIATION 17.2
44.3 years
STANDARD_DEVIATION 16.2
45.4 years
STANDARD_DEVIATION 15.3
45.3 years
STANDARD_DEVIATION 18.6
45.1 years
STANDARD_DEVIATION 16.5
Region of Enrollment
United States
44 participants37 participants38 participants39 participants158 participants
Sex: Female, Male
Female
21 Participants14 Participants22 Participants14 Participants71 Participants
Sex: Female, Male
Male
23 Participants23 Participants16 Participants25 Participants87 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —— / —
other
Total, other adverse events
11 / 5025 / 5015 / 5018 / 50
serious
Total, serious adverse events
0 / 500 / 500 / 500 / 50

Outcome results

Primary

Number of Patients With Pain Associated With Injection of Propofol.

Ten seconds following injection of propofol, subjects were asked Are you having pain at your IV site? Any behavioral signs were noted. Injection pain was assessed using the following four point scale: 0 = no pain; 1 = mild pain (pain reported only in response to questioning and without behavioral signs); 2 = moderate pain (pain reported in response to questioning and accompanied by a behavioral sign, or pain reported spontaneously without questioning); and 3 = severe pain (strong vocal response or response accompanied by facial grimacing, arm withdrawal, or tears).

Time frame: < 1 minute.

ArmMeasureValue (NUMBER)
LidocaineNumber of Patients With Pain Associated With Injection of Propofol.11 participants reporting pain
MagnesiumNumber of Patients With Pain Associated With Injection of Propofol.25 participants reporting pain
Lidocaine/MagnesiumNumber of Patients With Pain Associated With Injection of Propofol.15 participants reporting pain
ControlNumber of Patients With Pain Associated With Injection of Propofol.18 participants reporting pain
Primary

Percentage of Participants Reporting Pain With Injection of Propofol

Following injection of the study drug, 50 mg of propofol will be injected. Ten seconds after propofol, subjects will be asked a standard question about pain. Behavioral signs will be noted. Pain will be assessed using a four point scale: 0=no pain, 1=mild pain (pain reported only in response to questioning and without behavioral signs), 2=moderate pain (pain reported in response to questioning and a behavioral sign, or pain reported without questioning), 3=severe pain (strong vocal response or behavioral response).

Time frame: Approximately 10 seconds following administration of propofol.

ArmMeasureValue (NUMBER)
LidocainePercentage of Participants Reporting Pain With Injection of Propofol29 percentage of patients reporting pain
MagnesiumPercentage of Participants Reporting Pain With Injection of Propofol57 percentage of patients reporting pain
Lidocaine/MagnesiumPercentage of Participants Reporting Pain With Injection of Propofol41 percentage of patients reporting pain
ControlPercentage of Participants Reporting Pain With Injection of Propofol46 percentage of patients reporting pain

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026