|Year : 2014 | Volume
| Issue : 4 | Page : 545-549
The effect of addition of different doses of ondansetron to lidocaine as a component of intravenous regional anesthesia: a randomized double-blinded controlled study
Nahla S El Bahnasawy
Department of Anaesthesia and Intensive Care, Faculty of Medicine, Mansoura University, Mansoura, Egypt
|Date of Submission||13-Jan-2014|
|Date of Acceptance||06-Feb-2014|
|Date of Web Publication||28-Nov-2014|
Nahla S El Bahnasawy
Department of Anaesthesia and Intensive Care, Faculty of Medicine, Mansoura University
Source of Support: None, Conflict of Interest: None
The aim of this study was to evaluate and compare the analgesic effect of adding two different doses (4or 8 mg) of ondansetron to lidocaine for intravenous regional anesthesia (IVRA).
Patients and methods
Ninety-nine patients were randomly assigned into three groups. IVRA was achieved with lidocaine 3 mg/kg 0.5% (C group) (n = 33), lidocaine 3 mg/kg 0.5% plus 4 mg ondansetron (O1 group) (n = 33) or lidocaine 3 mg/kg 0.5% plus 8 mg ondansetron (O2 group) (n = 33). Times of onset and offset of sensory and motor blockade and the time of tourniquet pain were recorded. Postoperative visual analogue scale, time to first dose, and total amount of supplementary analgesia (diclofenac) were recorded.
Significantly shorter onset times and longer recovery times of sensory and motor block were recorded in groups O1 and O2 compared with group C (P < 0.05) with no significant difference between groups O1 and O2. Delayed onset of tourniquet pain occurred in groups O1 and O2 compared with group C (P < 0.05) with a significant difference between groups O1 and O2. Eighteen patients required intraoperative fentanyl to control tourniquet pain in group C compared with 10 patients in group O1 and three patients in group O2, respectively. A significantly lower postoperative visual analogue scale score, a longer time to first dose and lower consumption of diclofenac were recorded in groups O1 and O2 compared with group C with a significant difference between groups O1 and O2. No adverse effects were noted in any patients.
Addition of ondansetron to lidocaine enhanced the performance of lidocaine when used in IVRA, prolonged postoperative analgesia and reduced intraoperative and postoperative analgesia. However, adding 8 mg ondansetron to lidocaine provided better analgesia than 4 mg.
Keywords: intravenous regional anesthesia, lidocaine, ondansetron
|How to cite this article:|
El Bahnasawy NS. The effect of addition of different doses of ondansetron to lidocaine as a component of intravenous regional anesthesia: a randomized double-blinded controlled study. Ain-Shams J Anaesthesiol 2014;7:545-9
|How to cite this URL:|
El Bahnasawy NS. The effect of addition of different doses of ondansetron to lidocaine as a component of intravenous regional anesthesia: a randomized double-blinded controlled study. Ain-Shams J Anaesthesiol [serial online] 2014 [cited 2021 May 6];7:545-9. Available from: http://www.asja.eg.net/text.asp?2014/7/4/545/145713
| Introduction|| |
Intravenous regional anesthesia (IVRA) has proven to be successful for surgery of extremities. It is a simple and reliable technique with a high success rate of 94-98% [1,2]. Lidocaine 0.5% is the local anesthetic used most frequently, but it has a relatively short duration of action after tourniquet release. Many researches have been conducted aiming to overcome the disadvantage of this type of block including tourniquet pain and insufficient postoperative analgesia using adjuvant drugs to potentiate local anesthetics such as NSAIDs , opioids such as meperidine,  morphine,  and fentanyl , (α2) agonists , neostigmine  and tramadol . Ondansetron, a selective serotonin subtype 3 (5-HT3) receptor antagonist, is currently used for the prophylaxis and treatment of postoperative nausea and vomiting in perioperative management [10,11]. Ondansetron was found to have a local anesthetic effect. It could block sodium channels similar to local anesthetics and has an antinociceptive effect. Ondansetron interferes with the peripheral effect of serotonin on nociception . It binds to the opioid μ receptors and acts as an agonist .
The aim of the current study was to evaluate the effects of adding two different doses (4 and 8 mg) of ondansetron to lidocaine during IVRA compared with lidocaine alone. The primary outcome was the time to first analgesic request; secondary outcomes included sensory and motor block onset and recovery, the pain score, analgesic requirements, and adverse effects in the first 24 h.
| Patients and methods|| |
The current randomized double-blind controlled study was conducted at Mansoura University Hospital, during the period between January and November 2012, with approval from the local research ethics committee; written informed consent was obtained from 99 ASA physical status I or II patients. They were scheduled for short-procedure surgery of the hand or the forearm. Patients were randomly assigned to one of the three groups for administration of either lidocaine 0.5% (group C, n = 33), lidocaine 0.5% plus 4 mg ondansetron (group O1, n = 33) or lidocaine 0.5% plus 8 mg ondansetron (group O2, n = 33) for IVRA. Patients with a history of significant cardiac, renal, hepatic or psychiatric disease, peripheral vascular or neurological disease, a positive history of coagulopathy or a history of allergy from local anesthetics as well as those receiving chronic analgesic therapy were excluded from the study. All patients had routine physical examination, investigation and baseline ECG. The patients and the anesthesiologist were unaware of the group assignment. An investigator who did not participate in data collection prepared the local anesthetic solution. On arrival in the operating room, routine monitoring devices were placed and the baseline arterial blood pressure, the heart rate and peripheral oxygen saturation (SpO 2 ) were recorded. An intravenous catheter (20 G) was inserted into a distal vein on the dorsum of the hand of the operative extremity for injection of the local anesthetic solution. An intravenous infusion of Ringer's solution was commenced in a vein of the contralateral arm. Patients received 2 mg midazolam for sedation. A double-cuff tourniquet was placed on the upper arm of the operative extremity, and its proximal tourniquet was inflated subsequent to exsanguination of the limb with an Esmarch bandage. Circulatory isolation of the operative arm was confirmed by inspection of the hand and by the absence of radial pulse. The proximal tourniquet was inflated to a pressure of 250 mmHg. An intravenous solution of either lidocaine 3 mg/kg 0.5% diluted with 0.9% normal saline to a volume of 40 ml (group C), lidocaine 3 mg/kg 0.5% plus ondansetron 4 mg diluted with normal saline to a volume of 40 ml (group O1), or lidocaine 3 mg/kg 0.5% plus ondansetron 8 mg diluted with normal saline to a volume of 40 ml (group O2) was injected over 1 min in a double-blind, randomized manner. Randomization was achieved through the computer and sealed envelopes. Onset and recovery of sensory blockade was assessed by the pinprick method at three separate areas on the hand, selected to represent the innervations of the ulnar, the median, and the radial nerves. Assessment was made by a blinded observer at 1-min intervals from the end of injection for the first 10 min and then every 30 min while in the postanesthesia care unit until the time of discharge.
Motor function was evaluated at 1-min intervals by asking the patient to flex and extend his wrist and fingers. When sensory and motor block was completed, the distal cuff was then inflated to 250 mmHg followed by release of the proximal cuff. Time to complain from the tourniquet pain was recorded starting after tourniquet inflation for each patient. The visual analogue scale (VAS) was used to evaluate tourniquet pain. Fentanyl 1 microgram/kg was given for relieving tourniquet pain if VAS was greater than 3. The tourniquet was not inflated for more than 90 min and was not deflated before 40 min of local anesthetic injection. At the end of surgery, the tourniquet was deflated by repeated inflation-deflation technique (deflating the tourniquet for 10 s followed by 1 min of reinflation for three times).
Time of regaining sensation and motor power was recorded just after the release of the tourniquet. Postoperatively, after tourniquet deflation, the pain intensity was assessed by a blinded observer to the patient study group with a 10-point linear VAS. A score of 0 was described as no pain, and a score of 10 as the worst imaginable pain. Pain was scored at 30 min, 1, 2, 4, 6, 8 and 12 h after operation. If the recorded VAS pain score was greater than 3, Diclofenac 75 mg was injected intramuscularly as an analgesic supplement, to be repeated every 12 h if needed. The total diclofenac consumption was recorded. Time to the first request for analgesic was used as an indicator of the duration of postoperative analgesia from the time of local anesthetic injection. Patients were asked to rate central nervous system side effects such as dizziness, tinnitus, and light headedness, and they were observed carefully for reduction of heart rate and arterial blood pressure by more than 15% intraoperatively at the same time points as those defined for VAS assessment postoperatively. Hypotension was considered if there was 30% decrease below the baseline for mean arterial blood pressure, and it was treated with intravenous ephedrine (5 mg bolus); bradycardia was treated with intravenous atropine 1 mg. If there was a decrease in arterial SpO 2 by less than 90%, it was treated with oxygen through a transparent face mask.
The sample size was calculated with a type (1b error probe) of 0.05 to attain 80% statistical power to reject the null hypothesis in favor of an alternative hypothesis. This sample size calculation yielded a total of 99 cases that will be distributed into three groups with 33 cases in each.
The statistical analysis was carried out using the statistical package for social sciences version 18 (SPSS Inc., Chicago, Illinois, USA). Data were expressed as mean (SD) or number (%). Data were tested for normality using the Kolmogorov-Smirnov normality test. The χ2 -test or the Fisher exact test were used as appropriate to analyze categorical variables. Nonparametric data were compared using the Mann-Whitney U-test. Repeated measurements were analyzed by a repeated-measures analysis of variance test, if normally distributed. For non-normally distributed data, the Wilcoxon's ranked sum test was used to compare between groups at each time point. A P value of less than 0.05 was considered statistically significant.
| Results|| |
Demographic data of studied groups are shown in Table 1. The groups were similar with respect to demographic data, the duration of surgery, and the total tourniquet time ([Table 1]). Onset times of sensory as well as motor block were significantly shorter in both O1 and O2 groups compared with group C (P < 0.05), with no significant difference between the O1 and the O2 groups ([Table 2]).
Sensory and motor block recovery times were significantly longer in both O1 and O2 groups compared with group C (P < 0.05), with an insignificant difference between O1 and O2 groups ([Table 2]).
Onset times of tourniquet pain were significantly longer in both groups O1 and O2 compared with group C (P < 0.05). Group O2 showed a significantly longer time of onset of tourniquet pain compared with group O1 (P < 0.05) ([Table 2]). The number of patients who required intraoperative fentanyl were 18 in group C, 10 in group O1, and three in group O2, with a significantly lower number in groups O1 and O2 compared with group C and a significantly lower number in O2 compared with O1 ([Table 2]). On arrival to the postanesthesia care unit, the three groups had similar VAS pain scores at 30 min and 1 h after tourniquet deflation with an insignificant difference between them. Postoperatively, groups O1 and O2 had significantly lower VAS pain scores compared with group C at 2 and 4 h and at 2, 4, 6, 8, and 12 h for O1 and O2 groups, respectively. There was a significant decrease in VAS in group O2 compared with O1 at 6, 8, and 12 h, postoperatively ([Figure 1]).
|Figure 1: The visual analogue scale of patients in the studied groups at different postoperative times. Values are represented as mean ± SD. *P < 0.05 is significant when compared with group C. Group C, control group; group O1, ondansetron 4 mg; group O2 ondansetron 8 m g.|
Click here to view
Time to first dose of supplementary analgesia (diclofenac sodium) was significantly longer in groups O1 and O2 compared with group C (P < 0.05) and there was a significant increase in the time of request of analgesia between O1 and O2 groups (P < 0.05) ([Table 3]). The postoperative analgesic consumption in the first 24 h was significantly less in groups O1 and O2 compared with group C. A significant decrease in postoperative analgesic consumption was noted in O2 compared with group O1 (P < 0.05) ([Table 3]).
|Table 3 Time to fi rst analgesic request and the total dose of analgesic consumption|
Click here to view
No adverse effects were noted in any patient in the three groups. No significant changes were noted in the hemodynamic measurements, the SpO 2 , and the respiratory rate between the studied groups throughout the study period.
| Discussion|| |
The current study revealed that addition of ondansetron either 4 or 8 mg to lidocaine for IVRA was accompanied by more rapid onset and delayed offset of sensory and motor block. The present study demonstrated that IVRA with 4 and 8 mg ondansetron added to lidocaine provided better surgical anesthesia, delayed onset of postoperative pain, and less postoperative consumption of supplementary analgesia, with more significance on increasing the ondansetron dose to 8 mg without causing significant side effects. Previous studies have shown that ondansetron has local anesthetic action. It blocks sodium channels like local anesthetics and is ~15 times more potent than lidocaine because 0.1% ondansetron produced a local anesthetic effect similar to 1.5% lidocaine, and this may add to its antiemetic effects . Tourniquet pain is a major problem that arises after the use of pneumatic tourniquet during surgical procedures involving upper or lower limbs. The mechanism by which tourniquet pain is elicited is unclear . Tourniquet inflation prevents whole body distribution of ondansetron. A study by Stratz and Muller showed that 5-HT3 receptor antagonists had anti-inflammatory effects due to their peripheral action and played a role in decreasing pain after surgical incision. It could also act as supplement or replacement of local anesthetics and corticosteroids . This was in agreement with the result of the current study as patients in both O1 and O2 groups showed a significant decrease in tourniquet pain and a significant decrease in the number of patients requiring intraoperative supplemental fentanyl analgesia, with a more significant analgesic effect with increasing ondansetron dose. Similar to these results, a previous study by Farouk  reported improvement in the quality of IVRA and prolongation in postoperative anesthesia up to 4 h on adding 4 mg ondansetron to lidocaine.
However, in our study, increasing the dose of ondansetron to 8 mg increased the duration of postoperative analgesia up to 12 h and decreased postoperative rescue analgesia significantly compared with 4 mg ondansetron. Some studies have revealed that ondansetron can reduce or block the antinociceptive effect of certain classical analgesics such as paracetamol [17,18] and tramadol [19,20] with diverse and unknown mechanisms of action, which was not in agreement with this study.
In contrast to this, Lu et.al.  proved that ondansetron does not attenuate the analgesic efficacy of nefopam. Chen et.al.  demonstrated a lower pain intensity and lower analgesic needs after intravenous ondansetron antiemetic prophylaxis in shoulder surgery. In line with the present study, previous study proved that other 5-HT3 antagonists such as tropisetron and alosetron have analgesic effects [23-25].
| Conclusion|| |
Addition of ondansetron 4 or 8 mg to lidocaine provided effective anesthesia, prolonged postoperative analgesia, and decreased postoperative analgesic consumption. Interdose comparison showed that 8 mg ondansetron was significantly better than 4 mg without significant adverse effects.
| Acknowledgements|| |
| References|| |
Brill S, Middleton W, Brill G, Fisher A. Bier's block;100 years old and still going strong! Acta Anaesthesiol Scand 2004; 48:117-122.
Choyce A, Peng P. A systematic review of adjuncts for intravenous regional anaesthesia for surgical procedure. Can J Anesth 2002; 49:32-45.
Steinberg RB, Reuben SS, Gardner G. The dose response relationship of ketorolac as a component of intravenous regional anaesthesia with lidocaine. Anesth Analg 1998; 86:791-793.
Armstrong PJ, Morton CP, Nimmo AF. Pethidne has a local anaesthetic action on peripheral nerves in vivo
. Anaesthesia 1993; 48:382-386.
Gupta A, Bjornsson A, Sjoberg F, Bengtsson M. Lack of peripheral analgesic effect of low-dose morphine during intravenous regional anaesthesia. Reg Anesth 1993; 18:250-253.
Pitkanen MT, Rosenberg PH, Pere PJ, Tuominen MK, Seppala TA. Fentanyl-prilocaine mixture for intravenous regional anaesthesia in patients undergoing surgery. Anaesthesia 1992; 47:395-398.
Gentili M, Bernard JM, Bonnet F. Adding clonidine to lidocaine for intravenous regional anaesthesia prevents tourniquet pain. Anesth Analg 1999; 88:1327-1330.
Kang KS, Jung SH, Ahn KR, Kim CS, Kim JE, Yoo SH. The effects of neostigmine added to ropivacaine for intravenous regional anaesthesia. Korean J Anesthesiol 2004; 47:649-654.
Barkin RL. Extended-release tramadol (ULTRAMER): a pharmacotherapeutic, pharmacokinetic, and pharmacodynamic focus on effectiveness and safety in patients with chronic/persistent pain. Am J Ther 2008; 15:157-166.
Diemunsch P, Gan TJ, Philip BK, Girao MJ, Eberhat L, Irwin NG, et al.
Aprepitant-PONV Protocol 091 International Study Group. Single- dose aprepitant vs. ondansetron for the prevention of postoperative nausea and vomiting: a randomized, double-blind phase 3 trial in patients undergoing open abdominal surgery. Br J Anaesth 2007; 99:202-211.
Rosow CE, Haspel KL, Smith SE, Grecu L, Bittner EA. Haloperodol versus ondansetron for prophylaxis of postoperative nausea and vomiting. Anesth Analg 2008; 106:1407-1409.
Ye JH, Mui WC, Ren J, Hunt EE. Ondansetron exhibits the properties of a local anesthetic. Anesth Analg 1997; 85:1116-1121.
Gregory RE, Ettinger DS. 5-HT3 receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting. A comparison of their pharmacology and clinical efficacy. Drugs 1998; 55:173-189.
Crews JC, Hilgenhurst G, Leavitt B, Denson DD, Bridenbaugh PO, Stuebing RC. Tourniquet pain: the response to the maintenance of tourniquet inflation on the upper extremity in the volunteers. Reg Anesth 1991; 16:314-317.
Stratz T, Muller W. The use of 5-HT3 receptor antagonists in various rheumatic diseases - a clue to the mechanism of action of these agents in fibromyalgia. Scand J Rheumatol Suppl 2000; 113:66-71.
Farouk S. Ondansetron added to lidocaine for intravenous regional anaesthesia. Eur J Anaesthesiol 2009; 26:1032-1036.
Libert F, Bonnefont J, Bourinet E, Doucet E, Alloui A, Hamon M, et al.
Acetaminophen: a central analgesic drug that involves a spinal tropistron-sensitive, non-5-HT(3) receptor-mediated effect. Mol Pharmacol 2004; 66:728-734.
Pickering G, Loriot MA, Libert F, Eschalier A, Beaune P, Dubray C. Analgesic effect of acetaminophen in humans: first evidence of a central serotonergic mechanism. Clin Pharmacol Ther 2006; 79:371-378.
Arcioni R, della Rocca M, Romano S, Romano R, Pietropaoli P, Gasparetto A. Ondansetron inhibits the analgesic effects of tramadol: a possible 5-HT(3) spinal receptor involvement in acute pain in humans. Anesth Analg 2002; 94:1553-1557.
Dursteler C, Masea A, Fernandez V, Pol O, Puig MM. Interaction between tramadol and two anti-emetics on onciception and gastrointestinal transit in mice. Eur J Pain 2006; 10:629-638.
Lu KZ, Shen H, Chen Y, Li MG, Tian GP, Chen J. Ondansetron does not attenuate the analgesic efficacy of nefopam. Int J Med Sci 2013; 10:1790-1794.
Chen YF, Yeh WL, Lee KH, Li MC, Yang TH, Huang HC, et al.
Intravenous ondansetron as antiemetic prophylaxis for postoperative nausea and vomiting after shoulder arthroscopy. Chang Gung Med J 2011; 34:205-212.
Farber L, Stratz TH, Bruckle W, Spath M, Pongratz D, Lautenschlager J, et al.
German Fibromyalgia Study Group. Short-term treatment of primary fibromyalgia with the 5-HT3 receptor antagonist tropisetron. Results of a randomized, double-blind, placebo-controlled multicenter trial in 418 patients. Int J Clin Pharmacol Res 2001; 21:1-13.
Camilleri M, Mayer EA, Drossman DA, Heath A, Dukes GE, McSorley D, et al.
Improvement in pain and bowel function in female irritable bowel patients with alosetron, a 5-HT3 receptor antagonist. Aliment Pharmacol Ther 1999; 13:1149-1159.
Muller W, Fiebich BL, Stratz T. 5-HT3 receptor antagonist as analgesic in rheumatic diseases. Z Rheumatol 2006; 65:548-552.
[Table 1], [Table 2], [Table 3]