Korean J Anesthesiol Search

CLOSE


Kwak, Chae, Lee, Kim, and Kim: Combination of nitrous oxide and lidocaine to prevent withdrawal after rocuronium in children

Abstract

Background

Pain at the site of rocuronium injection is a common side-effect in pediatric patients. This prospective, randomized, double-blind study evaluated the efficacy of a combination of nitrous oxide and lidocaine pretreatment on withdrawal response during rocuronium injection in children.

Methods

Sixty six pediatric patients, ages 5 to 12 years, were randomly assigned to two groups. The oxygen group received 100% oxygen, and the nitrous oxide group received 50% N2O in oxygen over 2 min. After anesthesia was induced with 2.5% thiopental sodium 5 mg/kg and manual occlusion of the forearm was performed, 1% lidocaine 1 mg/kg was injected over 15 sec. After the occlusion was released, 0.1% rocuronium 0.6 mg/kg was injected over 5 sec. Patient response to rocuronium injection was graded using a 4-point scale.

Results

Overall incidence of withdrawal movements was significantly lower in the nitrous oxide group (1 patients; 3.1%) than in the oxygen group (8 patients; 25.8%) (P = 0.013). No patient in the nitrous oxide group displayed arm or generalized movement (grade 3 or 4) associated with rocuronium injection.

Conclusions

This study demonstrated that a combination of inhaled 50% N2O in O2 and 1 mg/kg lidocaine pretreatment significantly reduced the incidence of rocuronium-induced withdrawal movements in pediatric patients compared with lidocaine pretreatment alone.

Introduction

Pain is a common side-effect reported by 50-80% of patients receiving rocuronium injection [1-3]. Severe withdrawal movements tend to occur more frequently in pediatric patients, possibly because small veins take longer to clear. It can be a troublesome situation when sudden flexion of wrist and elbow, or other generalized movement occurs during injection of rocuronium. Several methods have been applied in an attempt to decrease the incidence of withdrawal movement in children. These include lidocaine [3], ketamine [4], or opioid [5,6] injection prior to rocuronium injection. These, however, do not completely eliminate withdrawal movement in all cases. Nitrous oxide is a well-established, centrally-acting sedative and analgesic agent. However, use of nitrous oxide to reduce withdrawal movement after rocuronium in children has not been reported. Therefore, this prospective, randomized study evaluated the efficacy of a combination of nitrous oxide and lidocaine pretreatment on the withdrawal response during rocuronium injection in children.

Materials and Methods

This study was approved by the institutional review board, and informed parental consent was obtained. The study was conducted prospectively on 66 patients between the ages of 5 and 12 years, with ASA physical status I or II, undergoing general anesthesia for elective surgery. Patients with known allergy to local anesthetics, asthma, neurologic deficits, those receiving analgesics or sedatives within the previous 24 hours, or those crying on arrival in the operating room were excluded from this study. Three children were excluded due to crying and one due to failure of IV access. No premedication was administered before surgery. Before arriving at the operating room, a 22 or 24-gauge cannula was inserted in the dorsum of the hand, and its position was confirmed by the free flow of a dextrose/saline infusion by gravity. Upon arrival at the operating room, all patients were monitored with electrocardiogram, pulse oxymeter, non-invasive arterial pressure, and capnography. Patients were randomly assigned to two groups using a computer generated randomization table. Patients in the oxygen group (n = 33) were preoxygenated with 100% oxygen. Patients in the nitrous oxide group (n = 33) were preoxygenated with 50% N2O mixture in oxygen. The fresh gas flow was set at 6 L/min. Study gases were administrated with a face mask gently held on the patients' face, but with an effective seal. Patients in both groups were asked to breathe normally via a face mask for 2 min prior to induction. In both groups, anesthesia was induced with 2.5% thiopental sodium 5 mg/kg followed by a free flow of IV fluid until loss of consciousness. Thirty seconds later, manual occlusion of the forearm was performed with sufficient force to stop IV flow by gravity, and 1% lidocaine 1 mg/kg was injected over 15 sec while manual forearm pressure was maintained, then released, followed by injection of 0.1% rocuronium 0.6 mg/kg over 5 sec. Assisted mask ventilation with O2 (or mixture of O2 and N2O) was applied if desaturation was observed (SpO2 < 90%). All medications were injected into a port connected directly to the IV catheter while the IV tubing was clamped above the injection site. After injection of rocuronium, fluids were administrated at a gravity flow. No visible precipitation occurred in the transparent portion of the IV tubing. Patients, anesthesia providers, and investigators who scored the movements were blind to the gas mixture administered to patients (flowmeters were covered by cardboard). Patient response was graded by the investigator according to the scale proposed by Shevchenko et al. [3], as follows: 1 = no response, 2 = movement at the wrist only, 3 = movement/withdrawal involving arm only (elbow/shoulder), and 4 = generalized response, movement/withdrawal in more than one extremity. The investigator also recorded the incidence of coughing and breath holding. Once responses were graded, the study was terminated. Anesthesia was continued based on the decision of the anesthetist.
From previous studies [3], rocuronium induced-withdrawal movement after pretreatment with lidocaine was expected to be approximately 45%. Therefore, 30 subjects per group would be needed to decrease this incidence to 10% (power 80% and α = 0.05). The sample size was increased to 66 patients on assumption of a 10% dropout rate. Statistical analyses were performed using the statistical package (SPSS 13.0 for windows, SPSS Inc, Chicago, IL, USA). Data are presented as mean ± SD or number of patients. Patient characteristics were compared with Student's t-test or Fisher's exact test where appropriate. Incidence of withdrawal movement was analyzed with Fisher's exact test. A P value < 0.05 was considered significant.

Results

A total of 66 patients were initially enrolled in the study. One patient in the nitrous oxide group became excited and started crying, and two patients in the oxygen group did not complete the study due to unwillingness to cooperate. Hence, data for 63 patients is presented. No significant difference was observed in patient characteristics between the two groups (Table 1).
Incidence and grade of withdrawal movement are listed in Table 2. Overall incidence of withdrawal movements was significantly lower in the nitrous oxide group (1 patients; 3.1%) than in the oxygen group (8 patients; 25.8%) (P = 0.013). In the oxygen group, 4 and 2 patients showed arm withdrawal movement (grade 3) and generalized movement (grade 4), respectively. None of the patients in the nitrous oxide group displayed arm or generalized movement (grade 3 or 4) associated with rocuronium injection. There were no significant differences in the SpO2 between the two groups, and SpO2 remained above 90% throughout the study period.

Discussion

This study demonstrated that a combination of inhaled 50% N2O in O2 mixture and pretreatment of 1 mg/kg lidocaine significantly reduced the incidence of rocuronium-induced withdrawal movements in pediatric patients compared with lidocaine pretreatment alone.
The need to reduce withdrawal movement or pain during rocuronium injection has encouraged a number of different approaches using local anaesthetics, opioids, sodium bicarbonate and many other drugs [3-10]. Among these, one of the most popular methods is the pretreatment of lidocaine with or without tourniquet technique, as in propofol injection pain [11]. However, even using lidocaine, the incidence of rocuronium induced-withdrawal movements or pain has been reported to between 46% and 17.5% [3,7-10]. Incidence of withdrawal movement in our study, following lidocaine pretreatment alone was 25.8%, comparable findings from previous studies. Furthermore, incidence of withdrawal movements decreased to 3.1%, in addition to inhalation of 50% N2O mixture over 2 min, as well as lidocaine pretreatment. The central antinociceptive effects of nitrous oxide may prevent the pain that results from the local irritant effect of rocuronium [12]. N2O has been used as an analgesic and as an anesthesia, and is still widely used today. N2O has been reported to affect a variety of different receptors, including opioid [13], noradrenergic [14], acetylcholine [15], γ-aminobutyric acid (GABA) [16], and N-methyl-d-aspartate (NMDA) [17] receptors. However, the mechanisms underlying its unique pharmacodynamic profile have not yet been fully clarified. Moreover, it is believed that the different effects of N2O (analgesic, anxiolytic, amnestic, hallucinogenic, and sedative, among others) are mediated by different pathways. Opioid receptors in the periaqueductal gray, noradrenergic descending inhibitory pathways, and inhibitory interneurons in the spinal cord [18] are thought to be involved in the analgesic action of N2O. Because N2O-induced analgesic action could be indirectly achieved through mediation by different pathways, exposure time to N2O in this study (<5 min) may be insufficient for production of an adequate analgesic effect. Therefore, further study for elucidation of the analgesic effect of N2O might be needed.
On the other hand, the effect of lidocaine was more likely the result of local anesthetic 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 lidocaine until rocuronium was injected. Therefore, a limited amount of lidocaine injected reached systemic circulation. Ahmad et al. [9] 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 N2O, such as 70%, may cause side effects including excitement, dysphoria, nausea, restlessness and opisthotonic movements [19]. Concentrations of 15-45% N2O produce quantifiable and meaningful increases in the threshold for both sensation and tolerance of pain. At concentrations below 50%, the analgesic effect of N2O follows a linear dose response pattern [20], although cognitive and other psychological factors also have an influence. As a result, we chose to use a concentration of 50% N2O. In addition, we enrolled children older than 5 years because it was our experience that these children could perform tidal volume breath with masks on their faces. N2O is widely available, easy to administer, and relatively free of side effects, bringing it to the useful analgesic agent in pediatric patients. Nevertheless, in our study, one patient in the nitrous oxide group developed side effects that included excitement and crying. Although the effect of N2O can be quickly reversed by stopping the N2O, and the complication of inhaled N2O may be brief and benign, the possibility of this complication occurring with the use of N2O must be considered. Another potential concern with the use of N2O during induction would be unanticipated difficult airway and compromised preoxygenation. Although, previous study has found that preoxygenation with mixtures of oxygen and N2O can help to smooth induction without impairment of oxygenation [21], care should be taken for possible desaturation during anesthetic induction in children.
In conclusion, pretreatment of two different analgesic modalities, nitrous oxide and lidocaine, prevents withdrawal movement grade 3 and 4 (arm only and generalized movement) associated with rocuronium injection, and reduces overall incidence of withdrawal movement in children.

References

1. Steegers MA, Robertson EN. Pain on injection of rocuronium bromide. Anesth Analg 1996; 83: 203PMID: 8659757.
crossref
2. Borgeat A, Kwiatkowski D. Spontaneous movements associated with rocuronium: is pain on injection the cause? Br J Anaesth 1997; 79: 382-383. PMID: 9389860.
crossref pmid pdf
3. Shevchenko Y, Jocson JC, McRae VA, Stayer SA, Schwartz RE, Rehman M, et al. The use of lidocaine for preventing the withdrawal associated with the injection of rocuronium in children and adolescents. Anesth Analg 1999; 88: 746-748. PMID: 10195516.
crossref pmid
4. Liou JT, Hsu JC, Liu FC, Ching-Wah Sum D, Lui PW. Pretreatment with small-dose ketamine reduces withdrawal movements associated with injection of rocuronium in pediatric patients. Anesth Analg 2003; 97: 1294-1297. PMID: 14570640.
crossref pmid
5. Kim JY, Kim JY, Kim YB, Kwak HJ. Pretreatment with remifentanil to prevent withdrawal after rocuronium in children. Br J Anaesth 2007; 98: 120-123. PMID: 17065169.
crossref pmid pdf
6. Oh AY, Seo KS, Goo EK, Park YO, Kim SJ, Kim JH. Prevention of withdrawal movement associated with injection of rocuronium in children: comparison of remifentanil, alfentanil and fentanyl. Acta Anaesthesiol Scand 2007; 51: 1190-1193. PMID: 17711566.
crossref pmid
7. Memis D, Turan A, Karamanlioglu B, Sut N, Pamukcu Z. The prevention of pain from injection of rocuronium by ondansetron, lidocaine, tramadol, and fentanyl. Anesth Analg 2002; 94: 1517-1520. PMID: 12032018.
crossref pmid
8. Turan A, Memis D, Karamanlioglu B, Sut N, Pamukcu Z. The prevention of pain from injection of rocuronium by magnesium sulphate, lignocaine, sodium bicarbonate and alfentanil. Anaesth Intensive Care 2003; 31: 277-281. PMID: 12879672.
crossref pmid
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: 987-990. PMID: 15781511.
crossref pmid
10. Yavascaoglu B, Kaya FN, Ozcan B. Esmolol pretreatment reduces the frequency and severity of pain on injection of rocuronium. J Clin Anesth 2007; 19: 413-417. PMID: 17967668.
crossref pmid
11. Picard P, Tramér MR. Prevention of pain on injection with propofol: a quantitative systematic review. Anesth Analg 2000; 90: 963-969. PMID: 10735808.
crossref pmid
12. Gillman MA, Lichtigfeld FJ. Clinical role and mechanisms of action of analgesic nitrous oxide. Int J Neurosci 1998; 93: 55-62. PMID: 9604169.
crossref pmid
13. Fujinaga M. Mechanisms of nitrous oxide-induced analgesic effects. Int Congr Ser 2005; 1283: 132-136.
crossref pmid pmc
14. 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 α2-B adrenoceptors. J Neurosci 2000; 20: 9242-9251. PMID: 11125002.
crossref pmid pmc
15. 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: 1095-1101. PMID: 11020766.
crossref pmid
16. Hapfelmeier G, Zieglgansberger W, Haseneder R, Schneck H, Kochs E. Nitrous oxide and xenon increase the efficacy of GABA at recombinant mammalian GABAA receptors. Anesth Analg 2000; 91: 1542-1549. PMID: 11094015.
crossref pmid
17. Mennerick S, Jevtovic-Todorovic V, Todorovic SM, Shen W, Olney JW, Zorumski CF. Effect of nitrous oxide on excitatory and inhibitory synaptic transmission in hippocampal cultures. J Neurosci 1998; 18: 9716-9726. PMID: 9822732.
crossref pmid pmc
18. Maze M, Fujinaga M. Pharmacology of nitrous oxide. Best Pract Res Clin Anaesthesiol 2001; 15: 339-348.
crossref
19. Henderson JM, Spence DG, Komocar LM, Bonn GE, Stenstrom RJ. Administration of nitrous oxide to pediatric patients provides analgesia for venous cannulation. Anesthesiology 1990; 72: 269-271. PMID: 2405740.
crossref pmid
20. Benedetti C, Chapman CR, Colpitts YH, Chen AC. Effects of nitrous oxide concentration on event-related potentials during painful tooth stimulation. Anesthesiology 1982; 56: 360-364. PMID: 7072999.
crossref pmid
21. Khoo ST, Woo M, Kumar A. Preoxygenation techniques: the value of nitrous oxide. Acta Anaesthesiol Scand 1993; 37: 23-25. PMID: 8424288.
crossref pmid
Table 1
Patient Characteristics
kjae-58-446-i001.jpg

Values are mean ± SD or number of patients. No significant differences between the two groups were noted.

Table 2
Incidence and Grade of Withdrawal Movements Associated with Rocuronium Injection
kjae-58-446-i002.jpg

Values are number of patients (percentage). *P < 0.05 compared with group O2.



ABOUT
ARTICLE CATEGORY

Browse all articles >

BROWSE ARTICLES
AUTHOR INFORMATION
Editorial Office
101-3503, Lotte Castle President, 109 Mapo-daero, Mapo-gu, Seoul 04146, Korea
Tel: +82-2-792-5128    Fax: +82-2-792-4089    E-mail: journal@anesthesia.or.kr                

Copyright © 2024 by Korean Society of Anesthesiologists.

Developed in M2PI

Close layer
prev next