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Anesth Analg 2002;94:1517-1520
© 2002 International Anesthesia Research Society

ANESTHETIC PHARMACOLOGY

The Prevention of Pain from Injection of Rocuronium by Ondansetron, Lidocaine, Tramadol, and Fentanyl

Dilek Memis*, Alparslan Turan*, Beyhan Karamanlioglu*, Necdet Süt{dagger}, and Zafer Pamukçu*

Departments of *Anaesthesiology and {dagger}Biostatistics, Trakya University, Edirne, Turkey

Address correspondence and reprint requests to Dr. Dilek Memis, Trakya University Medical Faculty, Department of Anaesthesiology and Reanimation, 22030, Edirne, Turkey. Address e-mail to dilmemis{at}mynet.com


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
We compared the efficacy of ondansetron, lidocaine, tramadol, and fentanyl in minimizing pain caused by the injection of rocuronium in 250 patients. After tourniquet application on the forearm, the patients were given saline (3 mL) (Group 1, n = 50), ondansetron (4 mg) (Group 2, n = 50), lidocaine (30 mg) (Group 3, n = 50), tramadol (50 mg) (Group 4, n = 50), or fentanyl (100 µg) (Group 5, n = 50) diluted into a 3-mL solution. The occlusion was released after 20 s and rocuronium was injected over 10–15 s. The patients were observed and asked immediately if they had pain in the arm, and the response was assessed. Reactions such as discomfort and pain, withdrawal of the hand, and so on after the administration of rocuronium were recorded as side effects for 24 h. Ten patients in Group 1, 28 patients in Group 2, 37 patients in Group 3, 30 patients in Group 4, and 15 patients in Group 5 reported no pain. Light pain was seen in 11 patients in Group 1, 14 patients in Group 2, 11 patients in Group 3, 12 patients in Group 4, and 20 patients in Group 5. Moderate pain was seen in 15 patients in Group 1, 6 patients in Group 2, 2 patients in Group 3, 8 patients in Group 4, and 10 patients in Group 5. Severe pain was seen in 14 patients in Group 1, 2 patients in Group 2, 0 patients in Group 3, 0 patients in Group 4, and 5 patients in Group 5. Correlation determined with log-linear analysis found in Group 1 pain score 0 (P < 0.001), Group 1 pain score 1 (P < 0.001), and Group 3 pain score 0 (P < 0.001). We conclude that ondansetron, lidocaine, tramadol, and fentanyl decrease the level of rocuronium injection pain. Among these drugs, lidocaine is the most effective, whereas fentanyl is the least effective.

IMPLICATIONS: We compared the efficacy of ondansetron, lidocaine, tramadol, and fentanyl in minimizing the pain on injection of rocuronium in 250 patients. Ondansetron, lidocaine, tramadol, and fentanyl were effective in preventing and decreasing the level of rocuronium injection pain. Among these drugs, lidocaine was the most effective, and fentanyl was the least effective.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Pain on injection of rocuronium is common, occurring in 50%–80% of patients (1). We recently observed in some patients the occurrence of sudden flexion, lasting 10–20 s, of the wrist and arm into which rocuronium was infused. Although this compound is considered to be tolerated well during injection, severe burning can occur after IV injection (2,3).1

Ondansetron is an antiemetic drug that, upon the demonstration of its local anesthetic property, began to be used in the prevention of injection pain of propofol (4–6). Ye et al. (5) have demonstrated that ondansetron blocks sodium channels in the neurons of the rat brain and might serve as a prototype molecule for developing a novel series of local anesthetics. Several studies have tried to determine the concentration of lidocaine and fentanyl that most efficiently diminishes or eliminates pain from propofol and rocuronium injection (3,7–9).1 Tramadol is a synthetic analgesic that can be used to treat moderate and severe pain (10). Pang et al. (11) observed a local anesthetic effect with intradermal injection of tramadol and lidocaine, and Tsai et al. (12) demonstrated a local anesthetic-type effect by possible neural conduction blockage of tramadol on sciatic nerves of rats. Fentanyl showed a local analgesic effect in reducing the pain on propofol injection, but the mechanisms of action are unknown (13,14). We compared the efficacy of ondansetron, lidocaine, tramadol, and fentanyl in minimizing the pain caused by injection of rocuronium.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
Our hospital ethics committee approved the protocol, and written, informed consent was obtained from the patients. The study was conducted on 250 patients from ASA physical status I–II groups who were to undergo various elective hysteroscopy or arthroscopy operations. Patients with opioid and local anesthetic allergies, Parkinson’s disease, or weak, thin dorsal veins were excluded from the study.

The patients were randomly assigned to five groups. The study was designed to be randomized and double-blinded. A randomization list was generated, and identical syringes containing each drug were prepared by personnel blinded to the study, according to the list. No premedication was given. The patients were then taken into the operating room, the backs of both hands were catheterized with 20-gauge catheters, and the mean arterial pressure, SpO2, and heart rate were monitored. With the aim of keeping the drug within the vein, the forearm was squeezed with a tourniquet up to 70 mm Hg; the patients were administered saline (3 mL) (Group 1, n = 50), ondansetron 4 mg (Group 2, n = 50), lidocaine 30 mg (Group 3, n = 50), tramadol 50 mg (Group 4, n = 50), or fentanyl 100 µg (Group 5, n = 50), diluted into 3 mL of saline IV at ambient operating room temperature (20°C–22°C). The occlusion was released after 20 s and a tracheal intubating dose of 0.6 mg/kg of rocuronium at room temperature was injected over 10–15 s. The patients were observed and asked immediately if they had pain in the arm, and the response was assessed. Reactions such as discomfort and pain, tears in the eye, withdrawal of the hand, and so on after the administration of the rocuronium were recorded as side effects (15) (Table 1). Thirty seconds after the administration of rocuronium, 5 mg/kg of thiopental was administered IV. For the crystalloid infusion and other medication, the IV catheter opened in the alternate hand was used. Via orotracheal intubation, anesthesia was continued during 50% N2O/oxygen and isoflurane anesthesia. Within the first 24 h after the operation, the injection site was checked for any complications, such as pain, swelling, or allergic reactions, by an anesthesiologist who did not know which drug was administered.


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  		Table 1. Assessment of Pain During Injection of Rocuronium
 
In the statistical analysis, one-way analysis of variance was used for the demographic data. The global association between the rows and columns was determined by log-linear analysis. For pain scores, the appropriate {chi}2 test was used for paired comparison of groups. P < 0.05 was taken as a significant value.


   Results
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 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
No significant differences were found in terms of demographic criteria (Table 2). When group and pain variables were investigated with log-linear analysis, important correlations between groups and pain scores were determined (likelihood ratio, {chi}2 = 71.128, P = 0.000). This correlation was found in Group 1 pain score 0 (z = -4.75, P < 0.001), Group 1 pain score 1 (z = -2.47, P < 0.001), and Group 3 pain score 0 (z = 3.09, P < 0.001). This was the result of differences in pain intensity. According to our results, the most effective drug was lidocaine.


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  		Table 2. Characteristics of the Patients (mean ± sd)
 
Paired comparison of groups for pain scores is shown in Table 3. Statistically evaluated differences can be seen in Table 3. Ondansetron, lidocaine, tramadol, and fentanyl prevent or decrease the degree of rocuronium injection pain. We found the most effective drug to be lidocaine, whereas the least effective drug was fentanyl. Within the first 24 h after the operation, the injection site was checked for any complications, such as pain, swelling, or allergic reactions, but none was observed.


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  		Table 3. Distribution According to Intensity of Pain
 

   Discussion
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 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
Earlier reports described burning pain associated with the administration of rocuronium before the induction of anesthesia (1,2,16).1 These studies noted a brisk flexion of the elbow and wrist in patients after the induction of anesthesia. The incidence of pain on injection from rocuronium is frequent; reports suggest that 50%–80% of patients experience pain (1). Mencke et al. (17) found that the incidence and the degree of withdrawal reactions in response to the injection of rocuronium were more frequent in women than in men. Klement and Arndt (18) showed that acidic and alkaline solutions elicited pain at pH values of <4 and >11, respectively. Pain latency also decreased with increasing osmolality, acidity, and alkalinity. Rocuronium is supplied as an isotonic solution with a pH of 4. Injection pain is probably caused by the effect of the acidic pH of rocuronium (8,19). We also compared different pretreatment drugs, such as ondansetron, lidocaine, tramadol, and fentanyl. Lidocaine was the most effective in reducing pain, whereas fentanyl was the least effective.

Venous retention with a tourniquet is a technique often used for pretreatment of propofol injection pain (13,14,16). In our study we also used this technique.

Ondansetron is an antiemetic drug and a commonly used 5-hydroxytryptamine-3 antagonist (4). Ye et al. (5) have demonstrated that ondansetron blocks sodium channels in neurons of the rat brain and might serve as a prototype molecule for developing a novel series of local anesthetics. Ondansetron can block sodium channels similar to local anesthetics; peripheral 5-hydroxytryptamine-3 receptors are also involved in nociceptive pathways and have demonstrated binding at opioid µ receptors exhibiting agonist activity, thus resulting in a peripheral antinociceptive effect (5,20). Ondansetron also attaches to opioid µ receptors with agonist activity and may be effective in preventing injection pain caused by drugs such as propofol (20). Ambesh et al. (6) administered 2 mL (4 mg) of ondansetron to successfully prevent injection pain. Reddy et al. (21) found that pain from rocuronium and propofol was significantly reduced in the ondansetron (4 mg) and lidocaine (50 mg) groups compared with placebo and that pain was significantly less with lidocaine than with ondansetron. In our study, we used similar doses of ondansetron as Ambesh et al. (6) and Reddy et al. (21) and found that this method decreased but did not eliminate pain.

Lockey and Coleman1 reported marked discomfort in all patients who received 0.6 mg/kg of rocuronium IV immediately after an induction dose of propofol mixed with 20 mg of lidocaine; this discomfort seemed to be unrelated to the discomfort from propofol. Cheong and Wong (8) evaluated whether prior administration of lidocaine 10 or 30 mg IV decreased the incidence of injection pain. They found that both lidocaine 10 and 30 mg IV given before the administration of rocuronium significantly reduced the incidence and severity of pain from injection of rocuronium and that the larger dose was more effective. In our study we determined that 30 mg of lidocaine was the most effective in reducing pain.

Tramadol is an analgesic drug with central effects that produces an analgesic effect by preventing the norepinephrine uptake and release without activating all of the opioid receptors (22). Pang et al. (22) found that injection of 25 mg of tramadol IM has a local anesthetic effect. Pang et al. (23) also observed that 50 mg of tramadol IV prevents injection pain from propofol as compared with lidocaine. However, neither drug totally eliminates the pain. In our study, 50 mg of IV tramadol did not completely eliminate injection pain.

Joshi and Whitten (3) found that 2 mg of IV midazolam and 100 µg of fentanyl does prevent the pain associated with the injection of a defasciculating dose of rocuronium (0.06 mg/kg) in an unspecified number of adult patients. Borgeat et al. (24) found that 2 µg/kg of IV fentanyl is effective in reducing rocuronium injection pain. In our study, IV fentanyl 100 µg decreased the pain but was not as effective as ondansetron, lidocaine, or tramadol.

Klement and Arndt (18) showed that injection of acidic solutions causes pain. The authors noted that after injection of acidic solutions, perivenous edema developed immediately. In our study, we did not see such side effects.

We conclude that ondansetron, lidocaine, tramadol, and fentanyl were effective in decreasing the level of rocuronium injection pain. According to our study, lidocaine was the most effective drug, whereas fentanyl was the least effective, in reducing injection pain.


   Footnotes
 
1 Lockey D, Coleman P. Pain during injection of rocuronium bromide [abstract]. Anaesthesia 1995;50:474. Back


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Steegers MA, Robertson EN. Pain on injection of rocuronium bromide. Anesth Analg 1996; 83: 193–205.
  2. Moorthy SS, Dierdorf SF. Pain on injection of rocuronium bromide. Anesth Analg 1995; 80: 1067.
  3. Joshi GP, Whitten CW. Pain on injection of rocuronium bromide. Anesth Analg 1997; 84: 228–36.
  4. Deegan R. Ondansetron: pharmacology of a specific 5HT3-receptor antagonist. Am J Med Sci 1992; 304: 373–8.[ISI][Medline]
  5. Ye JH, Mui WC, Ren J, et al. Ondansetron exhibits the properties of a local anesthetic. Anesth Analg 1997; 85: 1116–21.[Abstract]
  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.[Abstract/Free Full Text]
  7. King SY, Davis FM, Wells JE, et al. Lidocaine for the prevention of pain due to injection of propofol. Anesth Analg 1992; 74: 246–9.[ISI][Medline]
  8. Cheong KF, Wong WH. Pain on injection of rocuronium: influence of two doses of lidocaine pretreatment. Br J Anaesth 2000; 84: 106–7.[Abstract/Free Full Text]
  9. Kobayashi Y, Tsuchida A, Kamada Y, et al. Effects of speed of injection on anesthesia induction with propofol and fentanyl. Masui 1999; 48: 847–51.[Medline]
  10. Vickers MD, O’Flaherty D, Szekely SM, et al. Tramadol: pain relief by an opioid without depression of respiration. Anaesthesia 1992; 47: 291–6.[ISI][Medline]
  11. Pang WW, Mok MS, Chang DP, et al. Intradermal injection of tramadol has local anesthetic effect: a comparison with lidocaine. Acta Anaesthesiol Sin 1998; 36: 133–6.[Medline]
  12. Tsai YC, Chang PJ, Jou IM. Direct tramadol application on sciatic nerve inhibits spinal somatosensory evoked potentials in rats. Anesth Analg 2001; 92: 1547–51.[Abstract/Free Full Text]
  13. Pang WW, Huang S, Chung YT, et al. Comparison of intravenous retention of fentanyl and lidocaine on local analgesia in propofol injection pain. Acta Anaesthesiol Sin 1997; 35: 217–21.[Medline]
  14. Pang WW, Mok MS, Huang S, Hwang MH. The analgesic effect of fentanyl, morphine, meperidine, and lidocaine in the peripheral veins: a comparative study. Anesth Analg 1998; 86: 382–6.[Abstract]
  15. McCrirrick A, Hunter S. Pain on injection of propofol: the effect of injectate temperature. Anaesthesia 1990; 45: 443–4.[ISI][Medline]
  16. Borgeat A, Kwiatkowski D. Spontaneous movements associated with rocuronium: is pain on injection the cause? Br J Anaesth 1997; 79: 382–3.[Abstract/Free Full Text]
  17. Mencke T, Beerhalter U, Fuchs-Buder T. Spontaneous movements, local reactions and pain on injection of rocuronium: a comparison between female and male patients. Acta Anaesthesiol Scand 2001; 45: 1002–5.[ISI][Medline]
  18. Klement W, Arndt JO. Pain on intravenous injection of some anaesthetic agents is evoked by the unphysiological osmolality or pH of their formulations. Br J Anaesth 1991; 66: 189–95.[Abstract/Free Full Text]
  19. Dhara SS. Vecuronium, like rocuronium, causes pain on injection. Br J Anaesth 1998; 88: 487.
  20. Gregory RE, Ettinger DS. 5-HT3 receptor antagonists for the prevention chemotherapy-induced nausea and vomiting: a comparison of their pharmacology and clinical efficacy. Drugs 1998; 55: 173–89.[ISI][Medline]
  21. Reddy MS, Chen FG, Ng HP. Effect of ondansetron pretreatment on pain after rocuronium and propofol injection: a randomised, double-blind controlled comparison with lidocaine. Anaesthesia 2001; 56: 902–5.[ISI][Medline]
  22. Pang WW, Mok MS, Chang DP, Huang MH. Local anesthetic effect of tramadol, metoclopramide, and lidocaine following intradermal injection. Reg Anesth Pain Med 1998; 23: 580–3.[ISI][Medline]
  23. Pang WW, Huang PY, Chang DP, Huang MH. The peripheral analgesic effect of tramadol in reducing propofol injection pain: a comparison with lidocaine. Reg Anesth Pain Med 1999; 24: 246–9.[ISI][Medline]
  24. Borgeat A, Kwiatkowski D, Ruetsch YA. Spontaneous movements associated with rocuronium injection: the effects of prior administration of fentanyl. J Clin Anesth 1997; 9: 650–2.[ISI][Medline]



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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press