Comparison of Effects of Ephedrine, Lidocaine and Ketamine with Placebo on Injection Pain, Hypotension and Bradycardia Due to Propofol Injection: A Randomized Placebo Controlled Clinical Trial
Propofol is a widely used anesthetic drug because of its minor complication and also its fast effect. One of most popular complication in using this drug is pain during injection that is more sever in new generation of its components (lipid-free microemulsion). Other complications of propofol are bradycardia and hypotension. This study compares 3 drugs with placebo in control of these complications of propofol. In this double blinded randomized placebo controlled trial 140 patient who were candidates for elective surgery were divided in 4 groups (35 patients in each groups) and drugs (ephedrine, lidocaine, ketamine and NaCl solution (as placebo) were tried on each group by a blinded technician and responses to drugs were evaluated under supervision of a blinded anesthesiologist. Pain after injection, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) were measured 5 times during anesthesia process of each patient. All gathered data were analyzed using t-test and Chi-square under SPSS software. Our data shows that in pain management all tested drugs can decrease pain significantly comparing with placebo (P=0.017). In control of hemodynamic parameters ephedrine could efficiently control SBP, DBP, MAP at the time 1 min after intubation. Based on our study ephedrine can be an appropriate suggestion for control of both pain and hemodynamic changes induced by propofol, although because of inconsistent result in other studies it is recommended to design a systematic review to draw a broader view on this issue.
Reich DL, Hossain S, Krol M, Baez B, Patel P, Bernstein A, Bodian CA. Predictors of hypotension after induction of general anesthesia. Anesth Analg 2005;101(3):622-8, table of contents.
Albertin A, Casati A, Federica L, Roberto V, Travaglini V, Bergonzi P, Torri G. The effect-site concentration of remifentanil blunting cardiovascular responses to tracheal intubation and skin incision during bispectral index-guided propofol anesthesia. Anesth Analg 2005;101(1):125-30, table of contents.
Devlin JW, Lau AK, Tanios MA. Propofol-associated hypertriglyceridemia and pancreatitis in the intensive care unit: an analysis of frequency and risk factors. Pharmacotherapy 2005;25(10):1348-52.
Vuyk J, Engbers FH, Burm AG, Vletter AA, Griever GE, Olofsen E, Bovill JG. Pharmacodynamic interaction between propofol and alfentanil when given for induction of anesthesia. Anesthesiology 1996;84(2):288-99.
Yamakage M, Iwasaki S, Satoh J, Namiki A. Changes in concentrations of free propofol by modification of the solution. Anesth Analg 2005;101(2):385-8, table of contents.
Kim KM, Choi BM, Park SW, Lee SH, Christensen LV,mZhou J, Yoo BH, Shin HW, Bae KS, Kern SE, Kang SH, Noh GJ. Pharmacokinetics and pharmacodynamics of propofol microemulsion and lipid emulsion after an intravenous bolus and variable rate infusion. Anesthesiology 2007;106(5):924-34.
Jung JA, Choi BM, Cho SH, Choe SM, Ghim JL, Lee HM, Roh YJ, Noh GJ. Effectiveness, safety, and pharmacokinetic and pharmacodynamic characteristics of microemulsion propofol in patients undergoing elective surgery under total intravenous anaesthesia. Br J Anaesth 2010;104(5):563-76.
Sim JY, Lee SH, Park DY, Jung JA, Ki KH, Lee DH, NohGJ. Pain on injection with microemulsion propofol. Br J Clin Pharmacol 2009;67(3):316-25.
Fragen RJ, de Grood PM, Robertson EN, Booij LH, Crul JF. Effects of premedication on diprivan induction. Br J Anaesth 1982;54(9):913-6.
McCrirrick A, Hunter S. Pain on injection of propofol: the effect of injectate temperature. Anaesthesia 1990;45(6):443-4.
Stokes DN, Robson N, Hutton P. Effect of diluting propofol on the incidence of pain on injection and venous sequelae. Br J Anaesth 1989;62(2):202-3.
Saadawy I, Ertok E, Boker A. Painless injection of propofol: pretreatment with ketamine vs thiopental,,meperidine, and lidocaine. Middle East J Anesthesiol 2007;19(3):631-44.
Gehan G, Karoubi P, Quinet F, Leroy A, Rathat C,Pourriat JL. Optimal dose of lignocaine for preventing painm on injection of propofol. Br J Anaesth 1991;66(3):324-6.
Ambesh SP, Dubey PK, Sinha PK. Ondansetron pretreatment to alleviate pain on propofol injection: a randomized, controlled, double-blinded study. Anesth Analg 1999;89(1):197-9.
Iyilikci L, Balkan BK, Gökel E, Günerli A, Ellidokuz H. The effects of alfentanil or remifentanil pretreatment on propofol injection pain. J Clin Anesth 2004;16(7):499-502.
Basaranoglu G, Erden V, Delatioglu H, Saitoglu L. Reduction of pain on injection of propofol using meperidine and remifentanil. Eur J Anaesthesiol 2005;22(11):890-2.
Han YK, Jeong CW, Lee HG. Pain reduction on injection of microemulsion propofol via combination of remifentanil and lidocaine. Korean J Anesthesiol 2010;58(5):435-9.
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;30(6):1113-9.
Fujii Y, Nakayama M. Prevention of pain due to injection of propofol with IV administration of lidocaine 40 mg + metoclopramide 2.5, 5, or 10 mg or saline: a randomized, double-blind study in Japanese adult surgical patients. Clin Ther 2007;29(5):856-61.
Sieber FE, Pauldine R. Geriatric anesthesia. In: Miller RD, editor. Millers Anesthesia. 7th ed. Philadelphia: Churchill Livingstone; 2010. p. 2261-76.
Brandes RP, Fleming I, Busse R. Endothelial aging. Cardiovasc Res 2005;66(2):286-94.
Pagel PS, Warltier DC. Negative inotropic effects of propofol as evaluated by the regional preload recruitablestroke work relationship in chronically instrumented dogs. Anesthesiology 1993;78(1):100-8.
Robinson BJ, Ebert TJ, O'Brien TJ, Colinco MD, Muzi M. Mechanisms whereby propofol mediates peripheral vasodilation in humans. Sympathoinhibition or directvascular relaxation? Anesthesiology 1997;86(1):64-72.
Rouby JJ, Andreev A, Léger P, Arthaud M, Landault C, Vicaut E, Maistre G, Eurin J, Gandjbakch I, Viars P. Peripheral vascular effects of thiopental and propofol in= humans with artificial hearts. Anesthesiology 1991;75(1):32-42.
Eren G, Çukurova Z, Tekdöş Y, Saygı Emir N, Sağnak N, Hergünsel O. Can IV ephedrine protect from hypotension and injection pain with propofol induction? Med J Bakirköy 2005;1(2):48-51.
Ozkoçak I, Altunkaya H, Ozer Y, Ayoğlu H, Demirel CB, Ciçek E. Comparison of ephedrine and ketamine in prevention of injection pain and hypotension due to propofol induction. Eur J Anaesthesiol 2005;22(1):44-8.
Rokhtabnak F, Pournajafian AR. Comparsion of effect of ephedrine and lidocaine on pain during injection of propofol. Canadian J Anesth 2006;53(supp 1):26358.
Cheong MA, Kim KS, Choi WJ. Ephedrine reduces the pain from propofol injection. Anesth Analg 2002;95(5):1293-6, table of contents.
Agarwal A, Dhiraaj S, Raza M, Singhal V, Gupta D, Ranjan R, Singh PK, Singh U. Pain during injection of propofol: the effect of prior administration of ephedrine. Anaesth Intensive Care 2004;32(5):657-60.
El-Tahan MR. Preoperative ephedrine counters hypotension with propofol anesthesia during valve surgery: a dose dependent study. Ann Card Anaesth 2011;14(1):30-40.
Vosoughian L, Sadeghi M, Movafegh A. Study on the effect of Ketamine with propofol in outpatient surgeries. J Urmia Univ Med Sci 2005:15(1):14-8. [Persian]
Park SH, Jeong ST, Tak YJ, Kim CS, Kim ST. A comparison of the hemodynamic changes and propofolinduced pain at two different doses of remifentanil in elderly patients. Korean J Anesthesiol 2010;58(6):532-6.
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