|Year : 2017 | Volume
| Issue : 2 | Page : 99-103
Efficacy of pretreatment with intravenous paracetamol and lidocaine on rocuronium injection pain: A randomized, double-blinded, placebo-controlled study
Maharabam Binarani, Yumnam Arunkumar Singh, Deban Singh Lairenlakpam, Sinam Manichandra Singh, Longjam Eshori, Neetu Sinam
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal, Manipur, India
|Date of Web Publication||20-Apr-2017|
C/o Dr. Somarendra Khumukcham, Brahmapur Nahabam, Bamon Leikai, Imphal - 795 001, Manipur
Source of Support: None, Conflict of Interest: None
Background: Pain and withdrawal movement during rocuronium injection are common. The present study was conducted to compare the effect of paracetamol and lidocaine in ameliorating rocuronium injection pain and withdrawal movements. Materials and Methods: With approval of the Institutional Ethics Committee, 135 adult patients of both sexes aged 18–65 years with American Society of Anesthesiologists I or II, undergoing general anesthesia, were recruited to this randomized, double-blinded, placebo-controlled study, and patients were randomly divided into three equal groups. A rubber tourniquet was applied to the arm with intravenous line to occlude the venous drainage. Then, one of the pretreatment solutions was given, Group P received 50 mg paracetamol, Group L received 40 mg lidocaine, and Group S received 5 ml normal saline. After 2-min, tourniquet was released, and subparalyzing dose of rocuronium bromide 0.06 mg/kg was given and pain assessed using a 4-point verbal rating scale. Anesthesia was induced using 2.5% thiopentone sodium, followed by giving the remainder of calculated dose of rocuronium. During and after injection of rocuronium, withdrawal movements were observed and graded on a 4-point scale. Results: The incidence of pain on injection of subparalyzing dose of rocuronium in paracetamol, lidocaine and saline groups was 35.5%, 20%, and 55.5%, respectively (P < 0.05). The incidence of withdrawal movements while giving the bolus dose of rocuronium in paracetamol, lidocaine, and saline was 35.6%, 28.8%, and 59.9%, respectively (P < 0.05). Conclusion: Both paracetamol and lidocaine were effective in reducing rocuronium injection pain and withdrawal movements, but lidocaine is more effective than paracetamol.
Keywords: Lidocaine, paracetamol, rocuronium injection pain, withdrawal movement
|How to cite this article:|
Binarani M, Singh YA, Lairenlakpam DS, Singh SM, Eshori L, Sinam N. Efficacy of pretreatment with intravenous paracetamol and lidocaine on rocuronium injection pain: A randomized, double-blinded, placebo-controlled study. J Med Soc 2017;31:99-103
|How to cite this URL:|
Binarani M, Singh YA, Lairenlakpam DS, Singh SM, Eshori L, Sinam N. Efficacy of pretreatment with intravenous paracetamol and lidocaine on rocuronium injection pain: A randomized, double-blinded, placebo-controlled study. J Med Soc [serial online] 2017 [cited 2021 Jan 18];31:99-103. Available from: https://www.jmedsoc.org/text.asp?2017/31/2/99/204828
| Introduction|| |
Rocuronium bromide, a monoquaternary steroid analog of vecuronium, is a nondepolarizing neuromuscular blocking drug and characterized by a rapid onset and intermediate duration of action. Because of its fastest onset of action among the nondepolarizing muscle relaxants, it is frequently used in anesthesia practice as an alternative to succinylcholine in situ ations, in which rapid control of airway is required. Pain on injection of some anesthetic drugs such as propofol and rocuronium is an undesirable side effect in clinical practice. Incidence of rocuronium injection pain in clinical practice is 50%–80%;, although the cause and mechanism of rocuronium-induced injection pain were unknown, the characteristics of pain are similar to the propofol-induced injection pain and the pain is at times severe, with a burning sensation. Rocuronium injection pain can elicit withdrawal movement of the arm or generalized movement of the body, even after loss of consciousness, during induction of anesthesia. These withdrawal movements may dislodge a venous catheter or cause injury during induction of anesthesia. Paracetamol is widely used for pain management and antipyresis as an alternative to aspirin and nonsteroidal anti-inflammatory drugs but its action at the molecular level remained largely unknown. It is believed to be centrally active, producing analgesia and antipyresis by inhibiting cyclooxygenase (COX) in the hypothalamus. From animal studies, its antinociceptive effects reflect a combination of peripheral and central actions resulting from COX-2 inhibition.,, The peripheral action of paracetamol suggests that intravenous (i.v) paracetamol with venous occlusion could decrease rocuronium injection pain. To reduce the pain, withdrawal, and unwanted complications due to rocuronium injection, various methods have been applied which include pretreatment with ondansetron, tramadol, fentanyl,, lidocaine, N2O,, paracetamol,,,, ketamine, thiopentone, etc.
Lidocaine has been found to attenuate the rocuronium injection pain in several studies.,,, Even though a higher dose of lidocaine was found to be effective, we are concerned with risks of higher dose of lidocaine as plasma concentration of >5 mcg/ml can cause toxicity. Earlier studies , comparing 40 mg of lidocaine and 50 mg of paracetamol documented reduction of pain or withdrawal movements only. In this randomized, double-blinded, placebo-controlled study, we aimed at comparing the effect of i.v paracetamol with that of lidocaine to prevent rocuronium-induced pain and withdrawal movement. Our secondary objective was to observe the pain, swelling, or allergic reactions during the operation and first 24 h after the operative procedure.
| Materials and Methods|| |
After obtaining approval from the Institutional Ethics Committee and written informed consent from the patients, the study was carried out in a tertiary care teaching hospital at Imphal during 2013–2015. One thirty-five adult patients of both sexes aged 18–65 years with American Society of Anesthesiologists I or II, undergoing general anesthesia, were included in this prospective randomized, double-blinded, placebo-controlled study. Patients with chronic pain syndromes, neurological deficits, vascular diseases, difficult venous access, infection on the dorsum of hand, history of allergic reaction to the study drugs, and who received analgesics or sedative drugs within 24 h before surgery were excluded from the study. Patients were randomly assigned into three groups (n = 45 in each group) using computer-generated randomization. Group P received 50 mg of paracetamol in 5 ml, Group L received 40 mg lidocaine diluted with 5 ml of saline, and Group S received 5 ml of 0.9% saline. Study drugs were prepared by an anesthetist not directly involved in the study. Preanesthetic evaluations and basic investigations were performed in all patients scheduled for elective surgeries. Patients posted for surgeries were given ranitidine 300 mg and alprazolam 0.25–0.5 mg orally the night before surgery.
Patients were premedicated with ranitidine 50 mg i.v 1 h before the surgery. On arrival in the operating room, they were monitored with electrocardiogram, noninvasive blood pressure, and pulse oximetry. A 20-gauge catheter was inserted into a vein on the dorsum of patient's nondominant hand and its position was confirmed by the free flow of lactated Ringer's solution infusion. The lactated Ringer's solution was infused at 100 ml/h, and after 5 min, infusion was stopped. The arm with the i.v line was elevated for 15 s for gravity drainage of venous blood. After occluding venous drainage using a rubber tourniquet on the upper arm just to negotiate the index finger of the investigator, one of the pretreatment solutions was injected by the investigator who was unaware of group assignments over a period of 10 s. None of the patients was informed about which pretreatment solution used. After 2 min, the venous occlusion was released, and a subparalyzing dose of rocuronium bromide 0.06 mg/kg (1 mg/ml) diluted with normal saline was given over 10 s. The patients were observed and asked immediately if they had pain in the arm, and the responses were assessed according to the 4-point verbal scale: 0, no pain; 1, mild pain (pain reported only in response to questioning without any behavioral sign); 2, moderate pain (pain reported in response to questioning and accompanied by behavioral signs); and 3, severe pain (strong vocal response or accompanied by facial grimacing). After the assessment of the rocuronium-induced pain using 4-point verbal scale, induction of anesthesia was continued with i.v 2.5% thiopental sodium 5 mg/kg injected over 10–15 s. After the loss of consciousness, as assessed by no verbal response and loss of eyelash reflex, the remainder of calculated dose of rocuronium bromide was injected over 5 s to facilitate endotracheal intubation. During and after the injection of rocuronium, withdrawal movements were observed by the investigator. Withdrawal movements were graded according to the following scale: 1, no response; 2, movements at wrist only; 3, movement/withdrawal involving arm only (elbow/shoulder); and 4, generalized response movement/withdrawal in more than one extremity (cough or breath holding). Then, anesthesia was maintained using i.v tramadol 100 mg, N2O/O2 (50:50), and isoflurane with intermittent positive pressure ventilation. Any other adverse effects such as pain, swelling, or allergic reaction were checked during the operation and first 24 h after the operative procedure.
Based on earlier study, assuming incidence of rocuronium injection pain to be 15% and 42% in the lidocaine and paracetamol groups, respectively, the sample size for our study was 45 in each group for α value (Type I error) of 5% or 0.05 and a β value (Type II error) of 0.2 using a computer-generated sample size calculation.
The data collected were analyzed using Statistical Package for Social Sciences (SPSS, Chicago, IL, USA), window-based version 20.0. Patient's characteristics were analyzed using one-way analysis of variance. Chi-square test and Kruskal–Wallis test were used for other statistical analysis (gender and injection pain or withdrawal movements). Comparison between the groups was done by Mann–Whitney test. P < 0.05 was considered significant.
| Results|| |
There were no statistically significant differences among groups regarding the demographic data [Table 1]. [Table 2] shows the distribution of intensity of pain among the three groups caused by subparalyzing dose of rocuronium. Twenty patients (44.4%) in Group S, 36 (80%) patients in Group L, and 29 (64.4%) patients in Group P did not have any pain on injection of subparalyzing dose of rocuronium. Twelve patients (26.7%) in Group S, 7 (15.6%) patients in Group L, and 10 (22.2%) patients in Group P had mild pain. Seven patients (15.6%) in Group S, 2 (4.4%) patients in Group L, and 5 (11.1%) patients in Group P had moderate pain. Six patients (13.3%) in Group S and 1 (2.2%) patient in Group P had severe pain. No patient had severe pain in Group L. The distribution of pain among the three groups was statistically significant (P < 0.05). Patients in Group L andPexperienced lesser pain on rocuronium injection compared with Group S. The intensity and incidence of rocuronium injection pain was significantly lower in Group L and P, compared with Group S (P = 0.001 and 0.03, respectively). However, reduction in rocuronium injection pain, comparing Group L and P, was statistically not significant (P = 0.081). [Table 3] shows the distributions of withdrawal movements and statistical tests among the three groups, i.e., Group S, L, and P. Eighteen patients (40%) in Group S, 32 (71.1%) patients in Group L, and 29 (64.4%) patients in Group P had no withdrawal movements. Fourteen patients (31.1%) in Group S, 11 (24.4%) patients in Group L, and 12 (26.7%) patients in Group P had movements at the wrist. Eleven patients (24.4%) in Group S, 2 (4.4%) patients in Group L, and 3 (6.7%) patients in Group P had arm withdrawal. Two patients (4.4%) in Group S and 1 (2.2%) patient in Group P had generalized movements. However, no patients in Group L had generalized withdrawal movement. The distribution of withdrawal movements among the three groups was statistically significant with P < 0.05. Patients in Group L and P experienced lesser withdrawal movements which is statistically significant compared with Group S (P = 0.001 and P= 0.009, respectively). However, reduction in withdrawal movements in Group L compared with Group P was statistically not significant (P = 0.440). The complications due to the i.v injection of the study drugs, such as pain, swelling, or allergic reaction, were not observed during the operation and after the first 24 h of the operation in any of the groups.
|Table 3: Distribution of withdrawal movements and statistical test among the three groups|
Click here to view
| Discussion|| |
The demographic profiles of the patients among the three groups were comparable. Pain on i.v injection of some anesthetic drugs, such as propofol and rocuronium, is an undesirable effect in clinical practice. The incidence of rocuronium injection pain has been reported to occur in 50%–80% of patients., Rocuronium-induced generalized spontaneous movements may even cause pulmonary aspiration. To reduce pain and withdrawal movements induced by i.v injection of rocuronium, various methods have been tried. In our study, we observed that the incidence of pain after injection of subparalyzing dose of rocuronium as 55.6% in Group S (saline), 20% in Group L (lidocaine), and 35.5% in Group P (paracetamol). A study conducted by Gulnaz et al. reported the incidence of rocuronium injection pain to be 68.3% (saline group), 15% (lidocaine 40 mg), and 41.7% (paracetamol 50 mg). We observed that the incidence of rocuronium injection pain in Group S and Group P was slightly lower than the results observed by Gulnaz et al., and the incidence of pain in Group L was higher than they observed. However, the overall incidence of rocuronium injection pain was significantly less in Group L than Group P and S. The slight difference in our findings with them may be due to difference in sample size, and we also used rubber tourniquet instead of pneumatic tourniquet for venous occlusion. Rubber tourniquet is easy to use, but it may have inconsistent pressure for different patients, a potential limitation of our study. Uzun et al. also conducted a study on i.v paracetamol for prevention of rocuronium injection pain and demonstrated that i.v paracetamol (50 mg) was effective in decreasing the intensity of rocuronium injection pain but not as effective as lidocaine. Memis et al. also conducted a study to compare the efficacy of ondansetron, lidocaine, tramadol, and fentanyl in minimizing pain caused by the injection of rocuronium where they found the incidence of rocuronium injection pain in lidocaine group (30 mg) to be 26%. In our study, we found the incidence of rocuronium injection pain in lidocaine group as 20% which may be due to the use of higher dose in our study.
Sharma et al. also observed the incidence of rocuronium injection pain in lidocaine group 22.5% when they compared lidocaine with or without nitrous oxide, which is similar to our findings. Sivakumar et al. also conducted a study on rocuronium injection pain where they compared lidocaine alone and lidocaine with nitrous oxide. They observed the incidence of rocuronium injection pain in lidocaine group 25% which is almost similar to our finding. The exact mechanism of rocuronium-induced pain has not been ascertained. However, various theories have been proposed to explain the etiology of this pain. Rocuronium bromide is formulated with sodium acetate, sodium chloride, or acetic acid to produce a solution of pH 4. Peripheral veins are innervated with polymodal C-nociceptors which are activated by the osmolality or pH of rocuronium solution. Another mechanism may be activation of the release of endogenous mediators such as histamine, kinin cascade, and other substances mediating inflammation.
In this study, we also noted the incidence of withdrawal movements among the three groups while giving the remainder of calculated dose of rocuronium after induction of anesthesia with thiopentone 2.5% (after giving the subparalyzing dose). The incidence was 59.9% in Group S, 28.8% in Group L, and 35.6% in Group P. Similar study was also conducted by Jeon et al. where they observed the incidence of withdrawal movements 74.4% in saline group, 30.8% in lidocaine group, and 35.5% in paracetamol group. Incidence of withdrawal movements in lidocaine and paracetamol group was almost similar to our findings. Polat et al. compared the effect of paracetamol (50 mg) and lidocaine (0.5 mg/kg) for prevention of withdrawal movement associated with injection of rocuronium in children and observed that paracetamol reduces rocuronium-induced withdrawal movement but not as effective as lidocaine. Lui et al. reported a child who developed pulmonary aspiration secondary to gastric regurgitation caused by spontaneous movements after injection of rocuronium. Pain, emotional stress, and stimulation during induction of anesthesia may cause bronchospasm or myocardial ischemia and withdrawal movements which may dislodge the venous catheter or cause injury during induction of anesthesia.
Paracetamol can act centrally, as prostaglandin production in the brain is ten times more sensitive to inhibition by paracetamol than that in the spleen, although later studies showed different tissue effects. Abbott and Hellemans  showed the analgesic effects of paracetamol reflect central and peripheral actions. Lee et al. showed paracetamol inhibits COX-2 gene expression in a clinical model of acute inflammation. Hinz et al. showed paracetamol inhibits COX-2 activity in human blood cells and suppresses PGE2 generation in human blood monocytes. Thus, paracetamol inhibition of PGE2 may influence the intensity of rocuronium injection pain and withdrawal movements.
Lidocaine, a local anesthetic, reversibly blocks peripheral nerve pathways by blocking excitable membranes and is commonly used to reduce pain and withdrawal movements after rocuronium injection to 28%–46%. In this present study, lidocaine pretreatment reduces rocuronium injection pain and withdrawal movements to 20% and 28.8%, respectively. Ahmad et al. suggested that the central analgesic effect of a drug is only effective if adequate time is allowed for onset of analgesia, whereas pretreatment with drugs having local anesthetic properties is effective when administered immediately before, or with a venous occlusion technique. No side effects were observed with the use of the study drugs during the procedure.
We used rubber tourniquet which may have inconsistent pressure for different patients and no rescue medicine to alleviate injection pain and withdrawal movement of patients in saline group.
| Conclusion|| |
Our study reaffirmed earlier findings of reduction of rocuronium injection pain and withdrawal movements by both lidocaine and paracetamol. However, reduction in pain and withdrawal movements is more in lidocaine group than paracetamol though statistically not significant. Further studies are required to determine the optimal dose of i.v paracetamol and duration of venous occlusion to control rocuronium-induced pain and withdrawal movements.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Bartkowski RR, Witkowski TA, Azad S, Lessin J, Marr A. Rocuronium onset of action: A comparison with atracurium and vecuronium. Anesth Analg 1993;77:574-8.
Silverman DG, Mirakhur RK. Nondepolarizing relaxants of the 1990s. In: Silverman DG, editor. Neuromuscular Block in Perioperative and Intensive Care. Philadelphia: JB. Lippincott; 1994. p. 204-10.
Dalgleish DJ. Drugs which cause pain on intravenous injection. Anaesthesia 2000;55:828-9.
Borgeat A, Kwiatkowski D. Spontaneous movements associated with rocuronium: Is pain on injection the cause? Br J Anaesth 1997;79:382-3.
Steegers MA, Robertson EN. Pain on injection of rocuronium bromide. Anesth Analg 1996;83:203.
Lui JT, Huang SJ, Yang CY, Hsu JC, Lui PW. Rocuronium-induced generalized spontaneous movements cause pulmonary aspiration. Chang Gung Med J 2002;25:617-20.
Flower RJ, Vane JR. Inhibition of prostaglandin synthetase in brain explains the anti-pyretic activity of paracetamol (4-acetamidophenol). Nature 1972;240:410-1.
Abbott FV, Hellemans KG. Phenacetin, acetaminophen and dipyrone: Analgesic and rewarding effects. Behav Brain Res 2000;112:177-86.
Hinz B, Cheremina O, Brune K. Acetaminophen (paracetamol) is a selective cyclooxygenase-2 inhibitor in man. FASEB J 2008;22:383-90.
Memis D, Turan A, Karamanlioglu B, Sü t N, Pamukçu Z. The prevention of pain from injection of rocuronium by ondansetron, lidocaine, tramadol, and fentanyl. Anesth Analg 2002;94:1517-20.
Ahmad N, Choy CY, Aris EA, Balan S. Preventing the withdrawal response associated with rocuronium injection: A comparison of fentanyl with lidocaine. Anesth Analg 2005;100:987-90.
Sharma S, Sharma D, Jain A, Jain A. Effect of nitrous oxide on pain due to rocuronium injection: A randomised, double-blind, controlled clinical trial. Indian J Anaesth 2010;54:142-6.
] [Full text]
Sivakumar S, Singh NR, Singh LD, Rajkumar G, Thokchom RS, Devi LE. A comparative study of lignocaine and nitrous oxide from rocuronium injection pain. J Med Soc 2015;29:64-8. [Full text]
Jeon Y, Baek SU, Park SS, Kim SO, Baek WY, Yeo JS. Effect of pretreatment with acetaminophen on withdrawal movements associated with injection of rocuronium: A prospective, randomized, double-blind, placebo controlled study. Korean J Anesthesiol 2010;59:13-6.
Gulnaz A, Emine AK, Gosken OZ, Alpaslan A. Effect of paracetamol pretreatment on rocuronium induced injection pain: A randomized, double blind, placebo controlled comparison with lidocaine. J Clin Anal Med 2014;5:507-10.
Uzun S, Erden IA, Canbay O, Aypar U. The effect of intravenous paracetamol for the prevention of rocuronium injection pain. Kaohsiung J Med Sci 2014;30:566-9.
Polat R, Akin M, Keskin G, Ünal D, Dönmez A. Prevention of withdrawal movement associated with the injection of rocuronium in children: Comparison of paracetamol and lidocaine. Turk J Anaesthesiol Reanim 2016;44:86-90.
Akkaya T, Toygar P, Bedirli N, Yazicioglu D, Gumus H. Effects of pre-treatment with lidocaine or ketamine on injection pain and withdrawal movements of rocuronium. Turk J Med Sci 2008;38:577-2.
Park JT, Choi JC, Yoo YS, Lee YB, Kim SY, Lim HK. The effect of pretreatment with thiopental on reducing pain induced by rocuronium injection. Yonsei Med J 2005;46:765-8.
Cheong KF, Wong WH. Pain on injection of rocuronium: Influence of two doses of lidocaine pretreatment. Br J Anaesth 2000;84:106-7.
Klement W, Arndt JO. Pain on i.v. injection of some anaesthetic agents is evoked by the unphysiological osmolality or pH of their formulations. Br J Anaesth 1991;66:189-95.
Blunk JA, Seifert F, Schmelz M, Reeh PW, Koppert W. Injection pain of rocuronium and vecuronium is evoked by direct activation of nociceptive nerve endings. Eur J Anaesthesiol 2003;20:245-53.
Lee YS, Kim H, Brahim JS, Rowan J, Lee G, Dionne RA. Acetaminophen selectively suppresses peripheral prostaglandin E2 release and increases COX-2 gene expression in a clinical model of acute inflammation. Pain 2007;129:279-86.
[Table 1], [Table 2], [Table 3]