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

NCT01342510 | Completed Phase 4 Results DMC

• 1 other identifier: H-2010-0139
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

General Anesthesia; Intravenous Anesthesia

Keywords

Intravenous Anesthesia; General Anesthesia

Outcome Measures

Primary Outcomes (2)

• 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.

• 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.

Study Arms (4)

Lidocaine

EXPERIMENTAL

Lidocaine 50 mg in a 10 cc syringe

Drug: Magnesium Sulfate; Drug: Lidocaine

Magnesium

EXPERIMENTAL

Magnesium sulfate 0.25 g (2 mOsmol) in a 10 cc syringe

Drug: Magnesium Sulfate

Lidocaine/Magnesium

EXPERIMENTAL

Lidocaine 50 mg and 0.25 g (2 mOsmol) magnesium sulfate in a 10 cc syringe

Drug: Magnesium Sulfate; Drug: Lidocaine/Magnesium

Control

PLACEBO COMPARATOR

0.9% saline in a 10 cc syringe

Drug: Magnesium Sulfate; Drug: Control

Interventions

Magnesium Sulfate DRUG

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; Lidocaine; Lidocaine/Magnesium; Magnesium

Lidocaine DRUG

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

Control DRUG

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

Lidocaine/Magnesium DRUG

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Wisconsin, Madison: lead

Study Sites (1)

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Related Publications (20)

• Johnson RA, Harper NJ, Chadwick S, Vohra A. Pain on injection of propofol. Methods of alleviation. Anaesthesia. 1990 Jun;45(6):439-42. doi: 10.1111/j.1365-2044.1990.tb14328.x.

  PMID: 2200299 RESULT

• 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. doi: 10.1046/j.1365-2044.2000.01320.x.

  PMID: 10671850 RESULT

• 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. doi: 10.1034/j.1399-6576.2002.460816.x.

  PMID: 12190806 RESULT

• 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. doi: 10.1097/00000539-199907000-00035.

  PMID: 10389803 RESULT

• 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(3):235-8. doi: 10.1017/S026502150600202X. Epub 2007 Jan 4.

  PMID: 17202008 RESULT

• 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. doi: 10.1016/j.jclinane.2005.08.005.

  PMID: 16731324 RESULT

• 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.

  PMID: 18044291 RESULT

• Asik I, Yorukoglu D, Gulay I, Tulunay M. Pain on injection of propofol: comparison of metoprolol with lidocaine. Eur J Anaesthesiol. 2003 Jun;20(6):487-9. doi: 10.1017/s0265021503000784.

  PMID: 12803269 RESULT

• 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.2009.03.011.

  PMID: 20304348 RESULT

• 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 Ther. 2008 Feb;30(2):280-6. doi: 10.1016/j.clinthera.2008.02.018.

  PMID: 18343266 RESULT

• 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.clinthera.2008.05.019.

  PMID: 18640467 RESULT

• 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. doi: 10.1213/01.ane.0000103266.73568.18.

  PMID: 14980919 RESULT

• 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.

  PMID: 19696679 RESULT

• 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. doi: 10.1017/S026502150600233X. Epub 2007 Jan 30.

  PMID: 17261216 RESULT

• Ayoglu H, Altunkaya H, Ozer Y, Yapakci O, Cukdar G, Ozkocak I. Does dexmedetomidine reduce the injection pain due to propofol and rocuronium? Eur J Anaesthesiol. 2007 Jun;24(6):541-5. doi: 10.1017/S0265021506002250. Epub 2007 Jan 23.

  PMID: 17241503 RESULT

• Memis D, Turan A, Karamanlioglu B, Sut N, Pamukcu Z. The use of magnesium sulfate to prevent pain on injection of propofol. Anesth Analg. 2002 Sep;95(3):606-8, table of contents. doi: 10.1097/00000539-200209000-00020.

  PMID: 12198045 RESULT

• 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. doi: 10.1007/BF03018771.

  PMID: 14766688 RESULT

• Gajraj NM, Nathanson MH. Preventing pain during injection of propofol: the optimal dose of lidocaine. J Clin Anesth. 1996 Nov;8(7):575-7. doi: 10.1016/s0952-8180(96)00133-x.

  PMID: 8910180 RESULT

• 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. doi: 10.1007/s005400050015. No abstract available.

  PMID: 15235946 RESULT

• Tramer 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. doi: 10.1213/01.ane.0000263416.14948.dc.

  PMID: 17513629 RESULT

MeSH Terms

Interventions

Magnesium Sulfate; Lidocaine; Magnesium

Intervention Hierarchy (Ancestors)

Magnesium Compounds; Inorganic Chemicals; Sulfates; Sulfuric Acids; Sulfur Acids; Sulfur Compounds; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Metals, Alkaline Earth; Elements; Metals, Light; Metals

Limitations and Caveats

Problems with designation of ASA score differing from that given by anesthesiologist, insertion of a 20 gauge angiocatheter into the dorsum of the hand and anesthesia plan changing (general to monitored) prior to going to the operating room.

Results Point of Contact

• Title: Kristopher Schroeder, MD
• Organization: University of Wisconsin School of Medicine and Public Health, Department of Anesthesiology

kmschro1@wisc.edu

608-263-8100

Study Officials

• Kristopher M Schroeder, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2011
• First Posted: April 27, 2011
• Study Start: April 1, 2011
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: May 29, 2019
• Results First Posted: June 25, 2012

Record last verified: 2019-05

Locations

US (1)