- Email: [email protected]
The effects of alfentanil or remifentanil pretreatment on propofol injection pain
Original Contributions The Effects of Alfentanil or Remifentanil Pretreatment on Propofol Injection Pain Leyla Iyilikci, MD,* Bahar Kuvaki Balkan, MD,* Erol Go¨kel, MD,† Ali Gu¨nerli, MD,† Hu¨lya Ellidokuz, MD‡ Department of Anesthesiology, Dokuz Eylul University, School of Medicine, IzmirTurkey and Kocatepe University, School of Medicine, Department of Public Health; Afyon-Turkey
Study Objective: To compare the efficacy of alfentanil, remifentanil, and saline in minimizing the propofol injection pain. Design: Randomized, double-blind study. Setting: University hospital. Patients: 175 ASA physical status I and II, adult female patients undergoing minor gynecological procedures with general anesthesia. Interventions: Unpremedicated patients were randomly allocated to one of four groups. Patients received 2 mL (1 mg) of alfentanil (n ⫽ 43), 2 mL of remifentanil 0.01 mg (n ⫽ 43), 2 mL of remifentanil 0.02 mg (n ⫽ 45), or 2 mL of saline (n ⫽ 44) 30 seconds prior to administration 5 mL of propofol 1%. Measurements: Patients were asked whether they had pain due to propofol injection. Their pain scores were evaluated with a Visual Analogue Scale. In the Postanesthesia Care Unit, frequency of postoperative nausea, vomiting, hypotension, and flushing were all determined. Main Result: The remifentanil and alfentanil groups showed significantly less frequency and severity of pain than the saline group (p ⬍ 0.05). When the alfentanil group was compared with the remifentanil groups, significant differences in pain relief associated with injection of propofol (p ⬍ 0.001) were noted. Remifentanil 0.02 mg relieved pain associated with injection of propofol more effectively than remifentanil 0.01 mg (p ⬍ 0.001). Conclusions: The remifentanil and alfentanil groups showed significantly less frequency and severity of pain than did the saline group. Remifentanil was effective in preventing propofol injection pain, and should be used at a dose of at least 0.02 mg for this purpose. Remifentanil may be an alternative drug for prevention of propofol injection pain. © 2004 by Elsevier Inc. *Assistant Professor of Anesthesiology †Professor of Anesthesiology
Keywords: Anesthetics, propofol; opioid, alfentanil, remifentanil; complications, pain.
‡Assistant Professor of Anesthesiology Address correspondence to Dr. Iyilikci at Inonu cad. No: 264-2/12, 35280, Hatay/ Izmir-Turkey. E-mail: [email protected] Journal of Clinical Anesthesia 16:499 –502, 2004 © 2004 Elsevier Inc. All rights reserved. 360 Park Avenue, South, New York, NY 10010
Introduction Propofol has been widely accepted as an anesthetic of choice for ambulatory surgery.1,2 Pain induced during propofol injection is a common problem and 0952-8180/04/$–see front matter doi:10.1016/j.jclinane.2004.01.005
Original Contributions
Table 1. Characteristics of Study Patients and Duration of Anesthesia
Groups
n
Age (yrs)
Weight (kg)
Duration of anesthesia (min)
Alfentanil Remifentanil (0.01mg) Remifentanil (0.02 mg) Saline
43 43
42.3 ⫾ 10.9 47.1 ⫾ 9.6
67.0 ⫾ 12.7 68.5 ⫾ 10.5
37.3 ⫾ 22.4 39.1 ⫾ 17.3
45
44.5 ⫾ 7.8
68.3 ⫾ 8.8
39.7 ⫾ 15.6
44
44.4 ⫾ 7.5
68.5 ⫾ 8.0
36.4 ⫾ 5.7
Note: Values expressed are means ⫾ SD or numbers of patients, as appropriate.
can be very distressing to the patient. The incidence of this pain varies between 28% and 90% in adults, and may be severe.2,3 Many methods have been used to reduce this pain. Pretreatment with alfentanil, use of fentanyl, local anesthetics, metoclopramide, tramadol, ketamine, ondansetron, addition of lidocaine, ephedrine, granisetron, cooling or dilution of the propofol solution, and injection of propofol into a large antecubital vein or into a freely flowing intravenous (IV) line, are among the techniques described.1–13 The use of opioids, especially short-acting drugs such as alfentanil and fentanyl, was observed to decrease pain induced by propofol injection.2,9 –11 Remifentanil is a new, potent opioid used frequently in recent years.14,15 Remifentanil is a selective -opioid agonist, with a rapid and short effect. Its biological half-life is 3 to 10 minutes.14 To date, there are only a few studies of the effects of remifentanil in preventing propofol injection pain.16 –18 It has been reported that very low doses of remifentanil may prevent propofol injection pain. The purpose of this study was to compare the effects of pretreatment with two doses of remifentanil and alfentanil on pain during injection of propofol.
Materials and Methods Ethics Committee approval was obtained from Dokuz Eylul University School of Medicine, and all patients gave their informed consent. A total of 175 adult, female ASA physical status I-II patients, scheduled for minor gynecological procedures with general anesthesia, were enrolled into this randomized, double-blind study. Patients with a history of allergy, renal or hepatic problems, thrombophlebitis, or chronic pain for which they were taking sedative or analgesic medication, and those weighing less than 50 kg, were excluded from the study. Pregnant women and those requiring a rapid-sequence induction were also excluded. On arrival at the operating room (OR), a 20-gauge cannula was inserted into a vein on the dorsum of the patient’s nondominant hand, and a saline infusion was started at a rate of 5 mL kg h⫺1. Monitoring consisted of pulse oximetry, electrocardiography (lead II), and noninvasive blood pressure were applied (M1094B, Hewlett Packard, Saronno, Italy). Randomization was carried out using the table of random numbers. Patients were allocated to one of five groups, each group receiving either 2 500
J. Clin. Anesth., vol. 16, November 2004
mL (1mg) of alfentanil (n ⫽ 43, Group AL), 2 mL of remifentanil 0.01 mg (n ⫽ 43, Group REM1), 2 mL of remifentanil 0.02 mg (n ⫽ 45, Group REM2) or 2 mL of saline (n ⫽ 44, Group S) 30 seconds prior to administration of propofol. Thirty seconds after the intravenous (IV) injection of the pretreatment drug, 5 mL of 1% propofol (Fresenius Kabi, Hamburg, Germany) was injected IV at a rate of 0.5 mL/sec. A study-blinded anesthesiologist asked patients to evaluate their pain during propofol injection according to a 10-point Visual Analogue Scale (VAS), where 0 ⫽ no pain and 10 ⫽ intolerable pain. Induction of anesthesia was performed in all patients with propofol (total dose of 2 mg kg⫺1). Anesthesia was maintained using an inhalation technique (nitrous oxide 50% and sevoflurane 2–2.5% in oxygen) (Narkomed, North American Dra¨ger, Telford, PA). Any excitation during induction and reactions during emergence (eg, hypotension, nausea, vomiting, flushing) were recorded. Statistical analysis was carried out using SPSS for WINDOWS software program version 8.0 (SPSS, Chicago, IL). The Mann Whiney-U test was used to analyze the results of the patients’ subjective assessment of pain. A p-value less than 0.05 was considered statistically significant. Differences between scores from the saline group and the other groups was estimated as 1.5 and with a 0.05 ␣ error (two- sided) required sample size was 40 per group yielding a power higher than 90%.
Results There were no statistically significant differences among the groups with regard to age, weight and duration of anesthesia (p ⬎ 0.05) (Table 1). When compared with the saline group, the remifentanil and alfentanil groups showed significantly less frequency and severity of pain (p ⬍ 0.05; Figure 1). When the alfentanil group was compared to the remifentanil groups, we observed significant differences in relief of pain associated with propofol injection (p ⬍ 0.001). Remifentanil 0.02 mg relieved the pain associated with injection of propofol more effectively than remifentanil 0.01 mg (p ⬍ 0.001). No emergence reactions were observed in any of the treatment groups.
Alfentanil or remifentanil for propofol injection pain: Iyilikci et al.
Figure 1. Pain Scores during Injection of Propofol. ALalfentanil, REM1-remifentanil 0.01 mg, REM2-remifentanil 0.02 mg, S-saline. Pain scores are according to Visual Analog Scale (VAS), and evaluated by the patient during injection of propofol. Lowest pain scores were seen in the AL group and highest pain scores in the S group. #p ⬍ 0.05 for comparison between groups AL and REM2, REM1, S. *p ⬍ 0.001 for comparison between groups AL and REM2, REM1. ‡p ⬍ 0.001 for comparison between groups REM2 and REM1.
Discussion Pain on injection of propofol can be immediate or delayed; immediate pain probably results from a direct irritant effect whereas delayed pain likely is the result of an indirect effect via the Kinin cascade. Delayed pain has a latency of 10 –20 seconds.2 The ideal method for the prevention of propofol injection pain is still controversial. The literature reveals that pretreatment may prevent propofol injection pain. Nicol et al.19 found that oral premedication with benzodiazepines does not affect the frequency of pain, but Briggs et al.20 showed that pain frequency and severity decreases in cases treated with atropine and pethidine. In our study, we evaluated the direct effects of our method to propofol injection pain, without premedication, similar to the method applied by Nicol et al.19 Opioids such as alfentanil and fentanyl decreased the frequency of injection pain with propofol.2,9 –11 Remifentanil is an ultra short-acting opioid of the phenylpiperidine group, which may explain its pain-reducing actions.14 Remifentanil has potency 20 to 30 times greater than of alfentanil and shares common properties such as doserelated analgesia and central nervous system and respiratory depression.14,15 There are only a few studies, to date, of the effects of remifentanil on propofol injection pain.16 –18 Basaranoglu et al.16 evaluated propofol injection pain by administering remifentanil and fentanyl in a dose of 1 g kg⫺1 before propofol injection. They found no differences between groups. Roehm et al.17 compared the efficacy of continuous remifentanil infusion (0.25 g kg⫺1 min⫺1) with 40 mg lidocaine and placebo in the prevention of propofol injection pain due to IV administration. They reported that remifentanil relieves pain as effectively
as lidocaine. Kirdemir et al.18 compared various drugs to prevent propofol injection pain and concluded that remifentanil 0.5 g kg⫺1 or alfentanil one mg may be alternatives to lidocaine. In our study, lower doses of remifentanil were used and compared with the usually recommended alfentanil dose. Opioids show their effects either centrally or peripherally.2 Opioid receptors are found not only in the dorsal root ganglia and the central terminals of primary afferent nerves, but also in peripheral -opioid receptors, and their terminals. The reduction in injection pain might be the interaction of remifentanil or alfentanil with peripheral -opioid receptors.15 Helmers et al.10 found that pretreatment with fentanyl 0.1 mg or alfentanil one mg was equally effective in reducing pain. Nathanson et al.9 and Fletcher et al.11 showed that pretreatment with alfentanil one mg 15 and 30 seconds before propofol injection in adults significantly reduce propofol injection pain, and Roehm et al.17 reported this period for remifentanil infusion as 60 seconds. In our study, propofol was injected 30 seconds after remifentanil or alfentanil administration. As a result, when compared with the control group, the remifentanil and alfentanil groups showed significantly less frequency and severity of pain. In this study, we also found that remifentanil can be used to prevent propofol injection pain, and that it should be used in a dose of at least 0.02 mg for this purpose. We did not see any emergence reactions with remifentanil or alfentanil. To date, there are only a few studies comparing remifentanil with other opioids in preventing propofol injection pain, and further studies using different doses are needed. The combination of remifentanil with propofol is becoming more popular for ambulatory surgery, and therefore more knowledge about the effect of remifentanil on injection pain of propofol is advantageous.
References 1. Smith I, White PF, Nathanson M, Gouldson R: Propofol. An update on its clinical use. Anesthesiology 1994;81:1005–43. 2. Tan CH, Onsiong MK: Pain on injection of propofol. Anaesthesia 1998;53:468 –76. 3. Tan CH, Onsiong MK, Kua SW: The effect of ketamine pretreatment on propofol injection pain in 100 women. Anaesthesia 1998;53:302–5. 4. Mangar D, Holak EJ: Tourniquet at 50 mm Hg followed by intravenous lidocaine diminishes hand pain associated with propofol injection. Anesth Analg 1992;74:250 –2. 5. Shipton EA: Tramadol—Present and future. Anaesth Intensive Care 2000;28:363–74. 6. Ambesh SP, Dubey PK, Sinha PK: Ondansetron pretreatment to alleviate pain on propofol injection: A randomized, controlled, double-blinded study. Anesth Analg 1999;89:197–9. 7. Johnson RA, Harper NJ, Chadwick S, Vohra A: Pain on injection of propofol. Methods of alleviation. Anaesthesia 1990;45:439 –42. 8. Eriksson M, Englesson S, Niklasson F, Hartvig P: Effect of lignocaine and pH on propofol-induced pain. Br J Anaesth 1997;78:502–6. 9. Nathanson MH, Gajraj NM, Russell JA: Prevention of pain on injection of propofol: a comparison of lidocaine with alfentanil. Anesth Analg 1996;82:469 –71. 10. Helmers JH, Kraaijenhagen RJ, van Leeuwen L, Zuurmond WW: J. Clin. Anesth., vol. 16, November 2004
501
Original Contributions
11. 12. 13. 14.
15.
502
Reduction of pain on injection caused by propofol. Can J Anaesth 1990;37:267–8. Fletcher JE, Seavell CR, Bowen DJ: Pretreatment with alfentanil reduces pain caused by propofol. Br J Anaesth 1994;72:342–4. Cheong MA, Kim KS, Choi WJ: Ephedrine reduces the pain from propofol injection. Anesth Analg 2002;95:1293–6. Dubey PK, Prasad SS: Pain on injection of propofol: the effect of granisetron pretreatment. Clin J Pain 2003;19:121–4. Glass PS, Gan TJ, Howell S: A review of the pharmocokinetics and pharmacodynamics of remifentanil. Anesth Analg 1999;89(4 suppl):S7–14. Sebel PS, Hoke JF, Westmoreland C, Hug CC Jr, Muir KT, Szlam F: Histamine concentrations and hemodynamic responses after remifentanil. Anesth Analg 1995;80:1990 –3.
J. Clin. Anesth., vol. 16, November 2004
16. Basaranoglu G, Erden V, Delatioglu H: Reduction of pain on injection of propofol: A comparison of fentanyl with remifentanil. Anesth Analg 2002;94:1040 –1. 17. Roehm KD, Piper SN, Maleck WH, Boldt J: Prevention of propofol-induced injection pain by remifentanil:a placebo-controlled comparison with lidocaine. Anaesthesia 2003;58:165–70. 18. Kirdemir P, Gogus N: Comprasion of various drugs and techniques in the prevention of propofol injection pain. Gulhane Med J 2002;44:149 –53. 19. Nicol ME, Moriarty J, Edwards J, Robbie DS, A’Hern RP: Modification of pain on injection of propofol—a comparison between lignocaine and procaine. Anaesthesia 1991;46:67–9. 20. Briggs LP, White M: The effects of premedication on anaesthesia with propofol (‘Diprivan’). Postgrad Med J 1985;61(Suppl 3):35–7.
Study Objective: To compare the efficacy of alfentanil, remifentanil, and saline in minimizing the propofol injection pain. Design: Randomized, double-blind study. Setting: University hospital. Patients: 175 ASA physical status I and II, adult female patients undergoing minor gynecological procedures with general anesthesia. Interventions: Unpremedicated patients were randomly allocated to one of four groups. Patients received 2 mL (1 mg) of alfentanil (n ⫽ 43), 2 mL of remifentanil 0.01 mg (n ⫽ 43), 2 mL of remifentanil 0.02 mg (n ⫽ 45), or 2 mL of saline (n ⫽ 44) 30 seconds prior to administration 5 mL of propofol 1%. Measurements: Patients were asked whether they had pain due to propofol injection. Their pain scores were evaluated with a Visual Analogue Scale. In the Postanesthesia Care Unit, frequency of postoperative nausea, vomiting, hypotension, and flushing were all determined. Main Result: The remifentanil and alfentanil groups showed significantly less frequency and severity of pain than the saline group (p ⬍ 0.05). When the alfentanil group was compared with the remifentanil groups, significant differences in pain relief associated with injection of propofol (p ⬍ 0.001) were noted. Remifentanil 0.02 mg relieved pain associated with injection of propofol more effectively than remifentanil 0.01 mg (p ⬍ 0.001). Conclusions: The remifentanil and alfentanil groups showed significantly less frequency and severity of pain than did the saline group. Remifentanil was effective in preventing propofol injection pain, and should be used at a dose of at least 0.02 mg for this purpose. Remifentanil may be an alternative drug for prevention of propofol injection pain. © 2004 by Elsevier Inc. *Assistant Professor of Anesthesiology †Professor of Anesthesiology
Keywords: Anesthetics, propofol; opioid, alfentanil, remifentanil; complications, pain.
‡Assistant Professor of Anesthesiology Address correspondence to Dr. Iyilikci at Inonu cad. No: 264-2/12, 35280, Hatay/ Izmir-Turkey. E-mail: [email protected] Journal of Clinical Anesthesia 16:499 –502, 2004 © 2004 Elsevier Inc. All rights reserved. 360 Park Avenue, South, New York, NY 10010
Introduction Propofol has been widely accepted as an anesthetic of choice for ambulatory surgery.1,2 Pain induced during propofol injection is a common problem and 0952-8180/04/$–see front matter doi:10.1016/j.jclinane.2004.01.005
Original Contributions
Table 1. Characteristics of Study Patients and Duration of Anesthesia
Groups
n
Age (yrs)
Weight (kg)
Duration of anesthesia (min)
Alfentanil Remifentanil (0.01mg) Remifentanil (0.02 mg) Saline
43 43
42.3 ⫾ 10.9 47.1 ⫾ 9.6
67.0 ⫾ 12.7 68.5 ⫾ 10.5
37.3 ⫾ 22.4 39.1 ⫾ 17.3
45
44.5 ⫾ 7.8
68.3 ⫾ 8.8
39.7 ⫾ 15.6
44
44.4 ⫾ 7.5
68.5 ⫾ 8.0
36.4 ⫾ 5.7
Note: Values expressed are means ⫾ SD or numbers of patients, as appropriate.
can be very distressing to the patient. The incidence of this pain varies between 28% and 90% in adults, and may be severe.2,3 Many methods have been used to reduce this pain. Pretreatment with alfentanil, use of fentanyl, local anesthetics, metoclopramide, tramadol, ketamine, ondansetron, addition of lidocaine, ephedrine, granisetron, cooling or dilution of the propofol solution, and injection of propofol into a large antecubital vein or into a freely flowing intravenous (IV) line, are among the techniques described.1–13 The use of opioids, especially short-acting drugs such as alfentanil and fentanyl, was observed to decrease pain induced by propofol injection.2,9 –11 Remifentanil is a new, potent opioid used frequently in recent years.14,15 Remifentanil is a selective -opioid agonist, with a rapid and short effect. Its biological half-life is 3 to 10 minutes.14 To date, there are only a few studies of the effects of remifentanil in preventing propofol injection pain.16 –18 It has been reported that very low doses of remifentanil may prevent propofol injection pain. The purpose of this study was to compare the effects of pretreatment with two doses of remifentanil and alfentanil on pain during injection of propofol.
Materials and Methods Ethics Committee approval was obtained from Dokuz Eylul University School of Medicine, and all patients gave their informed consent. A total of 175 adult, female ASA physical status I-II patients, scheduled for minor gynecological procedures with general anesthesia, were enrolled into this randomized, double-blind study. Patients with a history of allergy, renal or hepatic problems, thrombophlebitis, or chronic pain for which they were taking sedative or analgesic medication, and those weighing less than 50 kg, were excluded from the study. Pregnant women and those requiring a rapid-sequence induction were also excluded. On arrival at the operating room (OR), a 20-gauge cannula was inserted into a vein on the dorsum of the patient’s nondominant hand, and a saline infusion was started at a rate of 5 mL kg h⫺1. Monitoring consisted of pulse oximetry, electrocardiography (lead II), and noninvasive blood pressure were applied (M1094B, Hewlett Packard, Saronno, Italy). Randomization was carried out using the table of random numbers. Patients were allocated to one of five groups, each group receiving either 2 500
J. Clin. Anesth., vol. 16, November 2004
mL (1mg) of alfentanil (n ⫽ 43, Group AL), 2 mL of remifentanil 0.01 mg (n ⫽ 43, Group REM1), 2 mL of remifentanil 0.02 mg (n ⫽ 45, Group REM2) or 2 mL of saline (n ⫽ 44, Group S) 30 seconds prior to administration of propofol. Thirty seconds after the intravenous (IV) injection of the pretreatment drug, 5 mL of 1% propofol (Fresenius Kabi, Hamburg, Germany) was injected IV at a rate of 0.5 mL/sec. A study-blinded anesthesiologist asked patients to evaluate their pain during propofol injection according to a 10-point Visual Analogue Scale (VAS), where 0 ⫽ no pain and 10 ⫽ intolerable pain. Induction of anesthesia was performed in all patients with propofol (total dose of 2 mg kg⫺1). Anesthesia was maintained using an inhalation technique (nitrous oxide 50% and sevoflurane 2–2.5% in oxygen) (Narkomed, North American Dra¨ger, Telford, PA). Any excitation during induction and reactions during emergence (eg, hypotension, nausea, vomiting, flushing) were recorded. Statistical analysis was carried out using SPSS for WINDOWS software program version 8.0 (SPSS, Chicago, IL). The Mann Whiney-U test was used to analyze the results of the patients’ subjective assessment of pain. A p-value less than 0.05 was considered statistically significant. Differences between scores from the saline group and the other groups was estimated as 1.5 and with a 0.05 ␣ error (two- sided) required sample size was 40 per group yielding a power higher than 90%.
Results There were no statistically significant differences among the groups with regard to age, weight and duration of anesthesia (p ⬎ 0.05) (Table 1). When compared with the saline group, the remifentanil and alfentanil groups showed significantly less frequency and severity of pain (p ⬍ 0.05; Figure 1). When the alfentanil group was compared to the remifentanil groups, we observed significant differences in relief of pain associated with propofol injection (p ⬍ 0.001). Remifentanil 0.02 mg relieved the pain associated with injection of propofol more effectively than remifentanil 0.01 mg (p ⬍ 0.001). No emergence reactions were observed in any of the treatment groups.
Alfentanil or remifentanil for propofol injection pain: Iyilikci et al.
Figure 1. Pain Scores during Injection of Propofol. ALalfentanil, REM1-remifentanil 0.01 mg, REM2-remifentanil 0.02 mg, S-saline. Pain scores are according to Visual Analog Scale (VAS), and evaluated by the patient during injection of propofol. Lowest pain scores were seen in the AL group and highest pain scores in the S group. #p ⬍ 0.05 for comparison between groups AL and REM2, REM1, S. *p ⬍ 0.001 for comparison between groups AL and REM2, REM1. ‡p ⬍ 0.001 for comparison between groups REM2 and REM1.
Discussion Pain on injection of propofol can be immediate or delayed; immediate pain probably results from a direct irritant effect whereas delayed pain likely is the result of an indirect effect via the Kinin cascade. Delayed pain has a latency of 10 –20 seconds.2 The ideal method for the prevention of propofol injection pain is still controversial. The literature reveals that pretreatment may prevent propofol injection pain. Nicol et al.19 found that oral premedication with benzodiazepines does not affect the frequency of pain, but Briggs et al.20 showed that pain frequency and severity decreases in cases treated with atropine and pethidine. In our study, we evaluated the direct effects of our method to propofol injection pain, without premedication, similar to the method applied by Nicol et al.19 Opioids such as alfentanil and fentanyl decreased the frequency of injection pain with propofol.2,9 –11 Remifentanil is an ultra short-acting opioid of the phenylpiperidine group, which may explain its pain-reducing actions.14 Remifentanil has potency 20 to 30 times greater than of alfentanil and shares common properties such as doserelated analgesia and central nervous system and respiratory depression.14,15 There are only a few studies, to date, of the effects of remifentanil on propofol injection pain.16 –18 Basaranoglu et al.16 evaluated propofol injection pain by administering remifentanil and fentanyl in a dose of 1 g kg⫺1 before propofol injection. They found no differences between groups. Roehm et al.17 compared the efficacy of continuous remifentanil infusion (0.25 g kg⫺1 min⫺1) with 40 mg lidocaine and placebo in the prevention of propofol injection pain due to IV administration. They reported that remifentanil relieves pain as effectively
as lidocaine. Kirdemir et al.18 compared various drugs to prevent propofol injection pain and concluded that remifentanil 0.5 g kg⫺1 or alfentanil one mg may be alternatives to lidocaine. In our study, lower doses of remifentanil were used and compared with the usually recommended alfentanil dose. Opioids show their effects either centrally or peripherally.2 Opioid receptors are found not only in the dorsal root ganglia and the central terminals of primary afferent nerves, but also in peripheral -opioid receptors, and their terminals. The reduction in injection pain might be the interaction of remifentanil or alfentanil with peripheral -opioid receptors.15 Helmers et al.10 found that pretreatment with fentanyl 0.1 mg or alfentanil one mg was equally effective in reducing pain. Nathanson et al.9 and Fletcher et al.11 showed that pretreatment with alfentanil one mg 15 and 30 seconds before propofol injection in adults significantly reduce propofol injection pain, and Roehm et al.17 reported this period for remifentanil infusion as 60 seconds. In our study, propofol was injected 30 seconds after remifentanil or alfentanil administration. As a result, when compared with the control group, the remifentanil and alfentanil groups showed significantly less frequency and severity of pain. In this study, we also found that remifentanil can be used to prevent propofol injection pain, and that it should be used in a dose of at least 0.02 mg for this purpose. We did not see any emergence reactions with remifentanil or alfentanil. To date, there are only a few studies comparing remifentanil with other opioids in preventing propofol injection pain, and further studies using different doses are needed. The combination of remifentanil with propofol is becoming more popular for ambulatory surgery, and therefore more knowledge about the effect of remifentanil on injection pain of propofol is advantageous.
References 1. Smith I, White PF, Nathanson M, Gouldson R: Propofol. An update on its clinical use. Anesthesiology 1994;81:1005–43. 2. Tan CH, Onsiong MK: Pain on injection of propofol. Anaesthesia 1998;53:468 –76. 3. Tan CH, Onsiong MK, Kua SW: The effect of ketamine pretreatment on propofol injection pain in 100 women. Anaesthesia 1998;53:302–5. 4. Mangar D, Holak EJ: Tourniquet at 50 mm Hg followed by intravenous lidocaine diminishes hand pain associated with propofol injection. Anesth Analg 1992;74:250 –2. 5. Shipton EA: Tramadol—Present and future. Anaesth Intensive Care 2000;28:363–74. 6. Ambesh SP, Dubey PK, Sinha PK: Ondansetron pretreatment to alleviate pain on propofol injection: A randomized, controlled, double-blinded study. Anesth Analg 1999;89:197–9. 7. Johnson RA, Harper NJ, Chadwick S, Vohra A: Pain on injection of propofol. Methods of alleviation. Anaesthesia 1990;45:439 –42. 8. Eriksson M, Englesson S, Niklasson F, Hartvig P: Effect of lignocaine and pH on propofol-induced pain. Br J Anaesth 1997;78:502–6. 9. Nathanson MH, Gajraj NM, Russell JA: Prevention of pain on injection of propofol: a comparison of lidocaine with alfentanil. Anesth Analg 1996;82:469 –71. 10. Helmers JH, Kraaijenhagen RJ, van Leeuwen L, Zuurmond WW: J. Clin. Anesth., vol. 16, November 2004
501
Original Contributions
11. 12. 13. 14.
15.
502
Reduction of pain on injection caused by propofol. Can J Anaesth 1990;37:267–8. Fletcher JE, Seavell CR, Bowen DJ: Pretreatment with alfentanil reduces pain caused by propofol. Br J Anaesth 1994;72:342–4. Cheong MA, Kim KS, Choi WJ: Ephedrine reduces the pain from propofol injection. Anesth Analg 2002;95:1293–6. Dubey PK, Prasad SS: Pain on injection of propofol: the effect of granisetron pretreatment. Clin J Pain 2003;19:121–4. Glass PS, Gan TJ, Howell S: A review of the pharmocokinetics and pharmacodynamics of remifentanil. Anesth Analg 1999;89(4 suppl):S7–14. Sebel PS, Hoke JF, Westmoreland C, Hug CC Jr, Muir KT, Szlam F: Histamine concentrations and hemodynamic responses after remifentanil. Anesth Analg 1995;80:1990 –3.
J. Clin. Anesth., vol. 16, November 2004
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