1 Department of Anesthesiology and Pain Medicine, 3B2.32 Walter C. Mackenzie Health Sciences Centre, University of Alberta Hospitals, 8440-112 Street, Edmonton, Alberta, Canada T6G 2B7. 2 Faculty of Pharmacy and Pharmaceutical Science, 3118 Dentistry-Pharmacy Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2N8
Corresponding authors: E-mail: dtjolly@compusmart.ab.ca and achiarel@ualberta.ca
Accepted for publication: October 21, 2002
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
Methods. Two hundred and fifty adult patients, ASA IIII, were randomized into five groups of 50 patients in a blinded, prospective study. The control group received rocuronium 10 mg alone. For the remaining four groups, rocuronium 10 mg was mixed with sodium bicarbonate 8.4% 2 ml, fentanyl 100 µg, lidocaine 2% or normal saline. The pH and osmolality of all mixtures were measured. Patient data were analysed using ordinal logistic regression. Osmolality and pH data were analysed using the KruskalWallis test with Dunns multiple comparison test.
Results. When compared with rocuronium alone, only the addition of saline failed to significantly reduce the pain reported by patients. The addition of fentanyl reduced the complaint of pain by 1.9 times (P<0.049) and the addition of lidocaine 2% reduced it by 3.6 times (P<0.0001). Sodium bicarbonate 8.4% reduced the reporting of pain by 18.4 times (P<0.0001).
Conclusions. Sodium bicarbonate 8.4%, when added to rocuronium, markedly reduces the experience of pain during the i.v. administration of a small dose of rocuronium.
Br J Anaesth 2003; 90: 3779
Keywords: anaesthetics, rocuronium; injection, pain; osmolality; pH
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
The purpose of this study was to determine the effectiveness of four strategies to reduce the pain associated with the i.v. administration of rocuronium 10 mg. The pH and osmolality of all study solutions were measured.
![]() |
Method and results |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
All patients received midazolam 1 mg followed by fentanyl 100 µg. Thirty seconds later the study mixture was administered. After another 30 s, the patient was asked if they experienced any pain or discomfort from the injection. Patients who responded positively were asked to rank their discomfort (Table 1). Patients were observed for signs of limb withdrawal, grimacing or crying. Immediately thereafter, propofol 2.0 mg kg1 was given.
|
Patient data were analysed using ordinal logistic regression. The response variable evaluated was the reported amount of injection pain. The controlled explanatory variables were the study solutions administered. Data were analysed for observational associations between pain scores and age, sex, height, weight, BMI and i.v. cannula gauge. The appropriateness of the ordinal logistic regression for the data analysed was confirmed by the Pearson and deviance of goodness-of-fit tests. The pH and osmolality data were analysed using the KruskalWallis test with Dunns multiple comparison test. The level of statistical significance selected was a P-value <0.05.
The age, weight, height and sex distribution were comparable in all groups. Despite i.v. premedication with midazolam 1 mg and fentanyl 100 µg, patients continued to report a substantial amount of pain with the i.v. injection of rocuronium. Rocuronium alone produced the highest reported pain response (Fig. 1). Sixty-six per cent of patients reported pain. Although the median pain score was 1 (mild), 30% reported the pain to be moderate to very severe. The addition of saline 0.9% or fentanyl 100 µg to rocuronium produced identical pain score distributions, with median pain scores of 1. In both these groups, 64% of patients reported pain and 14% reported the pain to be moderate to very severe. The odds ratio for reducing pain was 1.5 for saline and 1.9 for fentanyl. The addition of saline failed to significantly reduce the pain reported by patients. Although the addition of fentanyl achieved a P-value <0.05, this result is attributable to the influence of the outliers identified by the analysis. The addition of lidocaine 2% to rocuronium significantly reduced the pain and discomfort reported by patients (P<0.0001). The odds ratio was a 3.6 times reduction in reported pain. The median pain score for this group was 0. Forty-eight per cent of patients reported pain or discomfort with the administration of this mixture. However, only 8% reported the discomfort to be moderate to very severe. The addition of sodium bicarbonate 8.4% to rocuronium reduced the patients reported pain experience by 18.4 times (P<0.0001). The median pain score for the bicarbonate group was 0; 86% reported no discomfort on injection of this mixture. The remaining 14% reported only mild discomfort.
|
The pH of the rocuronium injectable was 4.0. When the pH of rocuronium alone was compared with the pH of the study mixtures, only rocuronium and sodium bicarbonate 8.4%, with a pH of 7.39, differed significantly (P<0.01). The osmolality of rocuronium was 280. The osmolalities of the mixtures of rocuronium and sodium bicarbonate 8.4% (osmolality 1200) and of rocuronium and fentanyl (osmolality 95) differed significantly from the osmolality of rocuronium (P<0.05).
![]() |
Comment |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
The aetiology of the discomfort caused by the i.v. administration of rocuronium is unknown. Peripheral veins are innervated with polymodal nociceptors that mediate the pain response to the injection of certain anaesthetic agents.8 Rocuronium is an isotonic solution with a pH of 4.0.2 Pain on injection has been associated with solutions with a pH of 4 or less.8 Consequently, it has been suggested that the injection pain produced by rocuronium is related to its low pH.2 4 Others have reported that the acid pH of rocuronium is not the cause of such pain.7 Because the preparation is isotonic, this physiochemical attribute probably does not contribute to the pain rocuronium produces. The addition of sodium bicarbonate 8.4% to rocuronium altered the pH and osmolality of the resulting mixture significantly. Whether the resulting changes in pH and osmolality were responsible for the marked reduction in pain reported by patients requires elucidation.
The purpose of this study was to evaluate strategies to reduce the pain associated with the administration of rocuronium. Rocuronium has been evaluated previously as a precurarization agent; it demonstrates superior effectiveness compared with d-tubocurarine, vecuronium, atracurium and mivacurium in preventing fasciculations and post-succinylcholine myalgias.9 The intense pain produced by rocuronium in patients has restricted its use as a precurarization agent. The addition of sodium bicarbonate 8.4% to a precurarization dose of rocuronium will resolve this problem.
![]() |
Acknowledgement |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
2 Lockey D, Coleman P. Pain during injection of rocuronium bromide. Anaesthesia 1995; 50: 474
3 Borgeat A, Kwiatkowski D. Spontaneous movements associated with rocuronium: is pain on injection the cause? Br J Anaesth 1997; 79: 3823
4 Cheong KF, Wong WH. Pain on injection of rocuronium: influence of two doses of lidocaine pretreatment. Br J Anaesth 2000; 84: 1067[Abstract]
5 Joshi GP, Whitten CW. Pain on injection of rocuronium bromide. Anesth Analg 1997; 84: 228
6 Shevchenko Y, Jocson JC, McRae VA, et al. The use of lidocaine for preventing the withdrawal associated with the injection of rocuronium in children and adolescents. Anesth Analg 1999; 88: 7468
7 Borgeat A, Kwiatkowski D, Ruetsch Y. Spontaneous movements associated with rocuronium injection: the effects of prior administration of fentanyl. J Clin Anesth 1997; 9: 6502[CrossRef][ISI][Medline]
8 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: 18995[Abstract]
9 Marten R, Carrier J, Pirlet M, et al. Rocuronium is the best non-depolarizing relaxant to prevent succinylcholine fasciculations and myalgia. Can J Anaesth 1998; 45: 5215[Abstract]