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

General Anesthesia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01342510
• Other study ID #: H-2010-0139
• Status: Completed
• Phase: Phase 4
• Start date: April 2011
• Est. completion date: April 2012

Study information

• Verified date: May 2019
• Source: University of Wisconsin, Madison
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: April 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• General Anesthesia
• Intravenous Anesthesia

Intervention

Drug:
• Magnesium 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.
• Lidocaine
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.
• Control
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.
• Lidocaine/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.

Locations

Country	Name	City	State
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
University of Wisconsin, Madison

Country where clinical trial is conducted

United States, 

References & Publications (20)

Agarwal A, Ansari MF, Gupta D, Pandey R, Raza M, Singh PK, Shiopriye, Dhiraj S, Singh U. Pretreatment with thiopental for prevention of pain associated with propofol injection. Anesth Analg. 2004 Mar;98(3):683-6, table of contents. — View Citation

Agarwal A, Dhiraj S, Raza M, Pandey R, Pandey CK, Singh PK, Singh U, Gupta D. Vein pretreatment with magnesium sulfate to prevent pain on injection of propofol is not justified. Can J Anaesth. 2004 Feb;51(2):130-3. — View Citation

Ambesh SP, Dubey PK, Sinha PK. Ondansetron pretreatment to alleviate pain on propofol injection: a randomized, controlled, double-blinded study. Anesth Analg. 1999 Jul;89(1):197-9. — View Citation

Apiliogullari S, Keles B, Apiliogullari B, Balasar M, Yilmaz H, Duman A. Comparison of diphenhydramine and lidocaine for prevention of pain after injection of propofol: a double-blind, placebo-controlled, randomized study. Eur J Anaesthesiol. 2007 Mar;24( — View Citation

Asik I, Yörükoglu D, Gülay I, Tulunay M. Pain on injection of propofol: comparison of metoprolol with lidocaine. Eur J Anaesthesiol. 2003 Jun;20(6):487-9. — View Citation

Ayoglu H, Altunkaya H, Ozer Y, Yapakçi O, Cukdar G, Ozkoçak I. Does dexmedetomidine reduce the injection pain due to propofol and rocuronium? Eur J Anaesthesiol. 2007 Jun;24(6):541-5. Epub 2007 Jan 23. — View Citation

Borazan H, Erdem TB, Kececioglu M, Otelcioglu S. Prevention of pain on injection of propofol: a comparison of lidocaine with different doses of paracetamol. Eur J Anaesthesiol. 2010 Mar;27(3):253-7. doi: 10.1097/EJA.0b013e328330eca2. — View Citation

Fujii Y, Itakura M. Comparison of lidocaine, metoclopramide, and flurbiprofen axetil for reducing pain on injection of propofol in Japanese adult surgical patients: a prospective, randomized, double-blind, parallel-group, placebo-controlled study. Clin Th — View Citation

Gajraj NM, Nathanson MH. Preventing pain during injection of propofol: the optimal dose of lidocaine. J Clin Anesth. 1996 Nov;8(7):575-7. — View Citation

Ghai B, Makkar JK, Bala I, Wig J. Effect of parecoxib pretreatment and venous occlusion on propofol injection pain: a prospective, randomized, double-blinded, placebo-controlled study. J Clin Anesth. 2010 Mar;22(2):88-92. doi: 10.1016/j.jclinane.2009.03.0 — View Citation

Huang YW, Buerkle H, Lee TH, Lu CY, Lin CR, Lin SH, Chou AK, Muhammad R, Yang LC. Effect of pretreatment with ketorolac on propofol injection pain. Acta Anaesthesiol Scand. 2002 Sep;46(8):1021-4. — View Citation

Ishiyama T, Kashimoto S, Oguchi T, Furuya A, Fukushima H, Kumazawa T. Clonidine-ephedrine combination reduces pain on injection of propofol and blunts hemodynamic stress responses during the induction sequence. J Clin Anesth. 2006 May;18(3):211-5. — View Citation

Johnson RA, Harper NJ, Chadwick S, Vohra A. Pain on injection of propofol. Methods of alleviation. Anaesthesia. 1990 Jun;45(6):439-42. — View Citation

Kwak K, Kim J, Park S, Lim D, Kim S, Baek W, Jeon Y. Reduction of pain on injection of propofol: combination of pretreatment of remifentanil and premixture of lidocaine with propofol. Eur J Anaesthesiol. 2007 Sep;24(9):746-50. Epub 2007 Jan 30. — View Citation

Kwak KH, Ha J, Kim Y, Jeon Y. Efficacy of combination intravenous lidocaine and dexamethasone on propofol injection pain: a randomized, double-blind, prospective study in adult Korean surgical patients. Clin Ther. 2008 Jun;30(6):1113-9. doi: 10.1016/j.cli — View Citation

Memis D, Turan A, Karamanlioglu B, Süt N, Pamukçu Z. The use of magnesium sulfate to prevent pain on injection of propofol. Anesth Analg. 2002 Sep;95(3):606-8, table of contents. — View Citation

Saadawy I, Ertok E, Boker A. Painless injection of propofol: pretreatment with ketamine vs thiopental, meperidine, and lidocaine. Middle East J Anaesthesiol. 2007 Oct;19(3):631-44. Erratum in: Middle East J Anesthesiol. 2008 Feb;19(4):919. — View Citation

Sasaki T, Okamura S, Kisara A, Ito M, Yogosawa K, Yagishita Y, Yogosawa T. Effect of lidocaine on pain caused by injection of propofol: comparison of three methods at two injection rates. J Anesth. 1999;13(1):14-6. — View Citation

Tramèr MR, Glynn CJ. An evaluation of a single dose of magnesium to supplement analgesia after ambulatory surgery: randomized controlled trial. Anesth Analg. 2007 Jun;104(6):1374-9, table of contents. — View Citation

Yull DN, Barkshire KF, Dexter T. Pretreatment with ketorolac and venous occlusion to reduce pain on injection of propofol. Anaesthesia. 2000 Mar;55(3):284-7. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
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).	Approximately 10 seconds following administration of propofol.
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).	< 1 minute.