|Year : 2015 | Volume
| Issue : 2 | Page : 64-68
A comparative study of lignocaine and nitrous oxide for rocuronium injection pain
Segaran Sivakumar, Nongthombam Ratan Singh, Lairenlakpam Deban Singh, Gojendra Rajkumar, Rupendra Singh Thokchom, Longjam Eshori Devi
Department of Anaesthesiology, Regional Institute of Medical Sciences (RIMS), Imphal, Manipur, India
|Date of Web Publication||20-Aug-2015|
Nongthombam Ratan Singh
Department of Anaesthesiology, Regional Institute of Medical Sciences (RIMS), Imphal - 795 004, Manipur
Source of Support: None, Conflict of Interest: None
Background: Pain is a common side effect of rocuronium bromide and this study has been undertaken to compare the effect of nitrous oxide and lignocaine in reducing the rocuronium injection pain in adult patients. Materials and Methods: After ethical committee approval, 80 adult patients of age 18-65 years and ASA I and II who underwent elective surgery from October 2011 and September 2013 in the Regional Institute of Medical Sciences, Imphal were randomly assigned into one of the two groups: Group O (n = 40) received 100% oxygen for 2 min as preoxygenation; Group N (n = 40) received 50% nitrous oxide and 50% oxygen mixture for 2 min as preoxygenation. After 2 min., 2 ml of 2% lignocaine was given with the forearm occluded and then released after 1 min. followed by the injection of subparalyzing dose of rocuronium (0.06 mg/kg) and the patients were enquired about the degree of pain. Anaesthesia was then induced with injection thiopentone sodium (2.5%) 5 mg/kg and then a paralyzing dose of rocuronium (0.6 mg/kg) was given to facilitate intubation. The airway was secured and any withdrawal movements were noted. Results: It was observed that the combination of nitrous oxide and lignocaine (Group N) reduced rocuronium injection pain more than lignocaine alone (Group O) (5% vs. 25%; P < 0.05). Moreover, withdrawal movements were also less in group N compared to group O (5% vs. 22.5%; P < 0.05). Conclusion: It may be concluded that two different analgesic modalities nitrous and lignocaine effectively prevent pain and withdrawal movements associated with rocuronium injection.
Keywords: Injection pain, lignocaine, nitrous oxide, rocuronium
|How to cite this article:|
Sivakumar S, Singh NR, Singh LD, Rajkumar G, Thokchom RS, Devi LE. A comparative study of lignocaine and nitrous oxide for rocuronium injection pain. J Med Soc 2015;29:64-8
|How to cite this URL:|
Sivakumar S, Singh NR, Singh LD, Rajkumar G, Thokchom RS, Devi LE. A comparative study of lignocaine and nitrous oxide for rocuronium injection pain. J Med Soc [serial online] 2015 [cited 2021 Jun 15];29:64-8. Available from: https://www.jmedsoc.org/text.asp?2015/29/2/64/163186
| Introduction|| |
Succinylcholine, the most widely used muscle relaxant of choice both for elective and rapid sequence intubation, has several adverse effects like myalgia, fasciculation, hyperkalemia, arrhythmia, raised intraocular, intracranial and intragastric pressure, etc. On the other hand, rocuronium a monoquaternary aminosteroid nondepolarizing neuromuscular blocking agent is comparable with succinylcholine for rapid sequence intubation with less adverse effects. It is also given in precurarization or priming techniques before the induction of anaesthesia. It provides intubating conditions almost similar to those seen with succinylcholine within 45-90 seconds with a dose 0.6 -1.2 mg/kg. But, it causes pain on intravenous injection with an incidence of 50-80%. ,
Various methods were used to alleviate the pain caused by rocuronium which include administration of lignocaine,  ketamine,  thiopentone,  ondansetron,  tramadol,  fentanyl,  esmolol,  dexmedetomedine,  acetaminophen,  magnesium sulphate  and nitrous oxide  prior to rocuronium injection with variable success rates.
Lignocaine produces analgesia by blockade of peripheral and central sodium ion gate channels, including those present in the spinal dorsal horn, and if given intravenously can alleviate deafferentation pain or central pain.  On the other hand, nitrous oxide, a centrally acting sedative and analgesic agent, has been used for several types of pain relief and painful procedures till now because of its cost effectiveness and easy availability.  The aim of the study was to determine the effect of nitrous oxide and lignocaine in reducing the incidence and severity of pain and withdrawal movements during injection of rocuronium in adult patients.
| Materials and Methods|| |
The study was a prospective, randomized and double-blinded study carried out in the department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal, Manipur during the period of two years (from October 2011 to September 2013) on patients undergoing general anaesthesia fulfilling the inclusion criteria were enrolled.
Patients with ASA (American society of Anaesthesiologists) physical status I or II, aged between18-65 years of both sexes.
Patients with chronic pain, known allergy to local anaesthetics, with respiratory diseases such as bronchial asthma or chronic obstructive pulmonary disease, neurological deficits, with anticipated difficult airway, thrombophlebitis, pregnancy, any contraindication to nitrous oxide, arrhythmias, known allergy to rocuronium and patients receiving analgesics or sedatives within the previous 24 hours.
To detect a fifty percent reduction at a significant level of 5% and a probability of 80%, this study required at least 40 patients per group, estimating the frequency of 80% of patients will experience pain or withdrawal movement on injection of rocuronium.  A randomization list was computer generated and patients were randomly allotted to two groups with equal number of patients (n = 40) in each group namely Group O and Group N according to this list.
After obtaining approval from institutional ethics committee and written informed consent, 80 patients of ASA physical status I and II of either sex, aged 18-65 years undergoing elective surgery under general anaesthesia enrolled for the study were allocated into two groups i.e. Group O: Received 100% oxygen and 2 ml of 2% lignocaine and Group N: Received 50% nitrous oxide - oxygen mixture and 2 ml of 2% lignocaine.
They were informed that they would be receiving a drug at the start of the anaesthetic procedure that may produce a burning sensation in their arm. The nature and function of the drug was explained to them. They were also explained that they had to tell their degree of pain as none, mild, moderate or severe according to McCrirrick and Hunter scale  after the drug had been administered.
On arrival at the operating room, all the patients were monitored with an electrocardiograph, pulse oximeter and an automatic noninvasive arterial blood pressure monitor. Intravenous access was secured with an 18G intravenous cannula preoperatively in the largest vein on the dorsum of the hand and an intravenous infusion of isotonic normal saline solution (0.9%) was started. All the patients posted for surgery received ranitidine 50 mg intravenous (i.v) and glycopyrolate 0.005 mg/kg intramuscular (i.m) 1 hour prior to the surgical procedure.
The patients were randomly assigned to one of the two groups using computer generated random sampling. Patients in Group O (n = 40) were preoxygenated with 100% oxygen, while those in Group N (n = 40) were administered a mixture of 50:50 nitrous oxide with oxygen. The fresh gas flow at 6 lit/min. was administered. Study gases were administered with a facemask gently held on the patients face, but with an effective seal. During this time, a screen was placed in front of the flow meters in such a fashion that the investigator collecting the data was blinded to the group assigned. Once the patient had inhaled 50% nitrous oxide - oxygen mixture (Group N) or pure oxygen (Group O) for two minutes, the forearm was occluded with a tourniquet (upto 70 mm Hg) to occlude the vein for 1 min, and 2% lignocaine 2 ml was injected over 15 seconds. After 1 min, the occlusion was released and a subparalysing dose of rocuronium 0.06 mg/kg (1 mg/ml) diluted with 0.9% normal saline was administered. The patients were observed and asked immediately if they had pain in the arm, and the response were assessed according to the McCrirrick and Hunter scale. Anaesthesia was then induced with 2.5% thiopentone 5 mg/kg i.v. till the eyelash reflex was abolished. An intubating dose of rocuronium 0.6 mg/kg was injected over 10 seconds to facilitate laryngoscopy and intubation and secure the airway, and withdrawal movements, if any, was recorded along with any adverse effects. The data collected was analyzed by using Statistical Package for Social Sciences (SPSS Inc., Chicago, IL, USA) Windows based version 16.0. The patient characteristics was analysed by using independent Student t-test. Chi-square test and Mann Whitney U test was used for other statistical analysis (gender and injection related pain or withdrawal movement). P-value ≤0.05 was deemed significant.
| Results|| |
There were no statistically significant difference in the demographic data (age, weight and sex) among two groups on comparing them using Student t-test and chi square test as shown in [Table 1].
[Table 2] shows the distribution of intensity of pain in the two groups caused by the subparalyzing dose of rocuronium. On injection of rocuronium, the incidence of no pain was 30(75%) in group O and 38 (95%) in group N; and the incidence of mild pain was 10 (25%) group O and 2 (5%) in group N respectively. No patient had moderate or severe pain in the two groups. The distribution of intensity of pain among two groups was statistically significant (P < 0.05). Group N patients experienced lesser pain when compared to patients in group O.
The distribution of withdrawal movements among two groups namely group O and group N is shown in [Table 3]. Thirty one patients (77.5%) in group O and thirty eight patients (95%) in group N had no withdrawal movements. 5 (12.5%) patients in group O had wrist withdrawal movements. No patients in group N had wrist withdrawal movements. 4 (10%) patients in group O and 2 (5%) patients in group N had arm withdrawal movements. No patients in both groups had generalized movement. In this study, the withdrawal movements were seen in 22.5% of the patients in group O and 5% in group N respectively. Overall, patients in group N experienced lesser withdrawal movements compared to group O.
|Table 3: Distribution of withdrawal movements and statistical test among two groups|
Click here to view
[Table 4] shows gender distribution of intensity of pain among two groups. In this study, 12 (80%) male patients and 18 (72%) female patients had no pain in group O; 3 (20%) male patients and 7 (28%) female patients had mild pain. Statistical analysis shows that gender distribution is not significant in group O (P > 0.05). In group N, 10 (100%) male patients and 28 (93.3%) female patients had no pain; no male patient and 2 (6.7%) female patients had mild pain in the same group. Statistical analysis shows that gender distribution is not significant in group N (P > 0.05).
| Discussion|| |
Pain is a common and distressing symptom of rocuronium injection and has been reported to range from 50-80% in different series of literature.  In this study, the incidence of mild pain after the subparalyzing dose of rocuronium in group O is 25% and 5% in group N which is similar to the study conducted by Sharma et al.  where they reported 22.5% in group O 2 and 2.5% in group N 2 O. They also reported that 37.5% of patients in group O and 5% of patients in group N had moderate pain, and also 2.5% of patients had reported severe pain in both the groups. In our study, no patients reported moderate or severe pain. The reason may be the use of combination of nitrous oxide and lignocaine which has additive and different analgesic modalities which reduced the incidence of pain whereas Sharma et al. used only 50% N 2 O in oxygen mixture for the prevention of pain.
The exact mechanism of rocuronium induced pain has not been ascertained. However, various theories have been proposed to explain the etiology of this pain which include: 
1. Rocuronium bromide is formulated with sodium acetate, sodium chloride or acetic acid to produce a solution (pH of 4). Peripheral veins are innervated with polymodal C- nociceptors which mediate the pain response. These receptors are activated by the osmolality or pH of the rocuronium solution which mediates pain.
2. Activation by 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 two groups. 22.5% patients in group O and 5% of patients in group N had withdrawal movements to the intubating dose of rocuronium (0.6 mg/kg). Sharma et al.  also demonstrated withdrawal movements in 15% of patients in group O 2 and 45% of patients in group N 2 O which is higher than our incidence. This might be because we used two drugs with different analgesic modalities namely lignocaine and nitrous oxide whereas they used only nitrous oxide as analgesic modality.
Kwak et al.  demonstrated that combination of nitrous oxide and lignocaine pre-treatment significantly reduced rocuronium induced withdrawal movements (3.1%) in paediatric patients compared to lignocaine pre-treatment alone (25.8%) which is similar to our study, where 5% had withdrawal movements in group N and 22.5% in group O.
Rocuronium can also cause pain even after induction of anaesthesia resulting in withdrawal movements. These withdrawal movements may negatively affect the patient outcome. Lui et al.  reported a child who developed pulmonary aspiration secondary to gastric regurgitation caused by spontaneous movements after the injection of rocuronium. Pain, emotional stress and stimulation during induction of anaesthesia may cause bronchospasm or myocardial ischaemia, and the withdrawal movements may dislodge the venous catheter or cause injury during induction.
The need to reduce pain or withdrawal movement during rocuronium injection has encouraged a number of different approaches like diluting rocuronium, administering as infusion rather than as a bolus, and the use of other medications such as various combinations of lignocaine, ondansetron, nitrous oxide, antihistaminics, opioids, sodium bicarbonate, ketamine, dexmedetomidine and esmolol. The most popular methods involve lignocaine or sodium bicarbonate pretreatment or mixing these drugs with rocuronium. However, even with the use of these drugs, the incidence of pain has been reported to be 20-25% with lignocaine. ,
The central antinociceptive effects of N 2 O may prevent the pain that results from the local irritant effect of rocuronium.  Nitrous oxide has been used as an analgesic and as an anaesthetic and is still widely used today, and has been reported to affect a variety of different receptors including opioid,  noradrenergic,  acetylcholine,  gamma amino butyric acid (GABA)  and N-methyl D-aspartate (NMDA)  receptors. However, the mechanisms underlying its unique pharmacodynamic profile have not yet been fully clarified. Moreover, it is believed that the different effects of N 2 O (analgesic, anxiolytic, hallucinogenic and sedative effects) are mediated by different pathways.
On the other hand, the effect of lignocaine was more likely the result of local anaesthetic effect at the site of injection, due to the fact that venous occlusion technique was applied to the forearm over 15 sec from time of injection of lignocaine until rocuronium was injected. Therefore, a limited amount of lignocaine injected reached systemic circulation. 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.
A high concentration of N 2 O, such as 70%, may cause side effects including excitement, dysphoria, nausea, restlessness and opisthotonic movements. Concentrations of 15-45% N 2 O produce quantifiable and meaningful increases in the threshold for both sensation and tolerance of pain. At concentrations below 50%, the analgesic effect of N 2 O follows a linear dose response pattern, although cognitive and other psychological factors also have an influence. As a result, we chose to use a concentration of 50% N 2 O. 
Mencke et al.  demonstrated that women experienced more pain on injection of rocuronium compared to males (45% vs. 20%) and concluded that some pretreatment is necessary especially in women, when considered using rocuronium, to prevent pain. In our study, we found that after pretreatment with either lignocaine alone or a combination of nitrous oxide and lignocaine, the incidence of pain in men and women was almost similar and not statistically significant (P > 0.05).
| Conclusion|| |
From this study, it may be concluded that nitrous oxide and lignocaine can be used for pretreatment to prevent rocuronium injection pain. Pretreatment with two different analgesic modalities viz. nitrous oxide and lignocaine prevents pain and withdrawal movements associated with rocuronium injection than when used alone.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Borgeat A, Kwiatkowski D. Spontaneous movements associated with rocuronium: Is pain on injection the cause? Br J Anaesth 1997;79:382-3.
Cheong KF, Wong WH. Pain on injection of rocuronium: Influence of two doses of lidocaine pretreatment. Br J Anaesth 2000;84:106-7.
Akkaya T, Toygar P, Bedirli N, Yazicioðlu D, Gumus H. Effects of pretreatment 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. Younsei Med J 2005;46:765-8.
Memis D, Turan A, Karamanlioðlu B, Süt N, Pamukçu Z. The prevention of pain from injection of rocuronium by ondansetron, lidocaine, tramadol and fentanyl. Anesth Analg 2002;94:1517-20, table of contents.
Yavascaoglu B, Kaya FN, Ozcan B. Esmolol pretreatment reduces the frequency and severity of pain on injection of rocuronium. J Clin Anesth 2007;19:413-7.
Ayoðlu H, Altunkaya H, Ozer Y, Yapakçi O, Cukdar G, Ozkoçak I. Does dexmedetomidine reduces the pain due to propofol and rocuronium? Eur J Anaesthesiol 2007;24:541-5.
Jeon Y, Baek SU, Park SS, Kim SO, Baek WY, Yeo JS. Effect of pretreatment with acetaminophen on withdrawal movement associated with injection of rocuronium: A prospective, randomized, double-blind, placebo controlled study. Korean J Anesthesiol 2010;59:13-6.
Shin YH, Choi SJ, Jeong HY, Kim MH. Evaluation of dose effects of Magnesium sulfate on rocuronium injection pain and haemodynamic changes by laryngoscopy and endotracheal intubation. Korean J Anaesthesiol 2011;60:329-3.
Kwak HJ, Chae YJ, Lee SK, Kim YJ, Kim JY. Combination of nitrous oxide and lidocaine to prevent withdrawal after rocuronium in children. Korean J Anesthesiol 2010;58:446-9.
Nagyl I, Woolf CJ. Lignocaine selectively reduces C fibre-evoked neuronal activity in rat spinalcord in vitro
by decreasing N-methyl-D-aspartate and neurokinin receptor-mediated post-synaptic depolarizations; implications for the development of novel centrally acting analgesics. Pain 1996;64:59-70.
Sawamura S, Kingery WS, Davies MF, Agashe GS, Clark JD, Kobilka BK, et al
. Antinociceptive action of nitrous oxide is mediated by stimulation of noradrenergic neurons in the brainstem and activation of [alpha]2B adenoceptors. J Neurosci 2000;20:9242-51.
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.
McCrirrick A, Hunter S. Pain on injection of propofol: The effect of injectate temperature. Anaesthesia 1990;45:443-4.
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.
Gillman MA, Lichtigfeld FJ. Clinical role and mechanisms of action of analgesic nitrous oxide. Int J Neurosci 1998;93:55-62.
Fujinaga M. Mechanisms of nitrous oxide-induced analgesic effects. Int Congr Ser 2005;1283:132-6.
Yamakura T, Harris RA. Effects of gaseous anesthetics nitrous oxide and xenon on ligand-gated ion channels. Comparison with isoflurane and ethanol. Anesthesiology 2000;93:1095-101.
Hapfelmeier G, Zieglgänsberger W, Haseneder R, SchneckH, Kochs E. Nitrous oxide and xenon increase the efficacy of GABA at recombinant mammalian GABA(A) receptors. Anesth Analg 2000;91:1542-9.
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.
MenckeT, Schreiber JU, Knoll H, Stracke C, Kleinschmidt S, Rensing H, et al
. Women report more pain on injection of a recurarization dose of rocuronium: A randomized, prospective, placebo-controlled trial. Acta Anaesthesiol Scand 2004;48:1245-8.
[Table 1], [Table 2], [Table 3], [Table 4]