Anesth Analg 2004;99:740-743
© 2004 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000130005.94395.B2
ANESTHETIC PHARMACOLOGY
Dilution of Rocuronium to 0.5 mg/mL with 0.9% NaCl Eliminates the Pain During Intravenous Injection in Awake Patients
Bahattin Tuncali, MD,
Ayse Karci, MD,
Binnur Erdalkiran Tuncali, MD,
Omur Mavioglu, MD,
Cimen Gulben Olguner, MD,
Selin Ayhan, MD, and
Zahide Elar, MD
Department of Anesthesiology and Reanimation, Dokuz Eylul University, 
zmir, Turkey
Address correspondence and reprint requests to Bahattin Tuncali, MD, Huzur mah, Sumbul sok, No. 42/11 Narlidere, zmir, Turkey. Address e-mail to bahattin.tuncali{at}deu.edu.tr
 |
Abstract
|
|---|
In a randomized, double-blinded, controlled study, we evaluated the effect of diluting rocuronium 10 mg/mL to 1 or 0.5 mg/mL with 0.9% NaCl on the pain associated with IV administration of rocuronium with small doses given before succinylcholine or nondepolarizing agent administration. One hundred fifty patients undergoing surgical procedures that required general anesthesia were randomized into three groups. Group 1 received rocuronium 10 mg/mL. Groups 2 and 3 received 1 and 0.5 mg/mL of rocuronium, respectively. Patient demographics, pain scores, osmolality, and the pH of the solutions were recorded. Group 1 had the most intense and frequent pain response. Eighty percent of patients in this group reported pain on injection. In Group 2, the incidence and intensity of pain were significantly less when compared with those of Group 1. In this group, 38% of patients reported pain during injection. In Group 3, none of the patients experienced pain on injection. The pH values and osmolalities of study solutions were not significantly different among groups. In conclusion, in awake patients, dilution of rocuronium 10 mg/mL at small doses given before succinylcholine or nondepolarizing agent administration of 0.06 mg/kg to 0.5 mg/mL with 0.9% NaCl is a simple and cost-effective strategy for preventing pain during IV rocuronium injection.
IMPLICATIONS: In awake patients, pain on injection of rocuronium during the induction of general anesthesia is common. The osmolality and pH of the solutions were the same in all groups. Dilution of rocuronium to 1 and 0.5 mg/mL with 0.9 % NaCl decreased or prevented the pain during IV injection.
|
Introduction
|
|---|
Rocuronium is a steroidal muscle relaxant of intermediate duration with a rapid onset time (1). To prevent fasciculations and postsuccinylcholine myalgias, a small dose of rocuronium is more effective than D-tubocurarine, vecuronium, atracurium, or mivacurium (2). However, the intense pain during injection of rocuronium has restricted its use for preventing some of the problems associated with succinylcholine (3–6). The etiology of pain caused by the IV administration of rocuronium is unknown. Pretreatment or mixing with a variety of drugs has been used in attempts to reduce this pain (7–13).
The aim of this study was to evaluate the effect of diluting rocuronium 10 mg/mL to 1 or 0.5 mg/mL with 0.9% NaCl on the pain associated with IV administration of rocuronium with small doses given before succinylcholine or nondepolarizing agent administration.
|
Methods
|
|---|
After obtaining informed consent from the patients and approval from the institutional ethics committee, we studied 150 patients undergoing surgical procedures that required general anesthesia. Exclusion criteria included age <18 yr and allergy to any of the anesthetic medications being administered. Patients were informed that they would receive a drug at the beginning of their anesthetic that might cause a burning pain in their arm. They were told that they would be asked to score the severity of pain, if any occurred, after the drug had been injected. The patients were also informed that they could experience side effects such as heavy eyelids, blurred vision, or difficulty in swallowing and breathing after injection of the drug. They were asked to report if any of the side effects occurred. No premedication was administered.
On arrival at the operating room, an 18-gauge cannula was placed in a vein on the dorsum of the hand, and an IV infusion of 0.9% NaCl was started. Standard monitoring was used. Patients were randomly allocated to one of three groups by using sealed envelopes. Group 1 (n = 50) received rocuronium 0.06 mg/kg (10 mg/mL), Group 2 (n = 50) received rocuronium 0.06 mg/kg (1 mg/mL) diluted with 0.9% NaCl, and Group 3 (n = 50) received rocuronium 0.06 mg/kg (0.5 mg/mL) diluted with 0.9% NaCl, by using 10-mL syringes. All syringes were prepared by another investigator and were covered so that the investigator who assessed the patient’s response was unaware of the nature of the solution. All injections were performed in 5 s. Ten seconds after injection of the study drug, the patients were asked if they experienced pain or discomfort during the injection. Patients who responded positively were asked to rank their pain on a five-point scale (14) (Table 1). Patients were also observed for signs of limb withdrawal, grimacing, or crying. Because the administration of IV rocuronium may cause unpleasant effects, an IV hypnotic drug was administered immediately thereafter until loss of consciousness, and anesthesia proceeded as planned.
The pH and osmolality of the solutions were measured with a pH meter (Hanna Instruments 9321 microprocessor) and osmometer (Osmomat 030-D; Gonotec GmbH, Berlin, Germany). Measurements were performed on three samples of each solution.
In the statistical analysis, one-way analysis of variance was used for demographic data. For pain scores, the 
2 test was used for comparison of groups. P < 0.05 was taken as a significant value.
|
Results
|
|---|
One hundred fifty patients were included in the study. The demographic characteristics (age, body mass index, and sex distribution) were not statistically different among groups (Table 2).
Group 1 (rocuronium 10 mg/mL) produced the most intense and frequent reported pain response. Eighty percent of patients in this group reported pain on injection. Although the median pain score was 2 (moderate), 36% of patients reported the pain to be severe to very severe. In Group 2, dilution of rocuronium to 1 mg/mL with 0.9% NaCl significantly reduced the incidence and intensity of pain compared with Group 1. In this group, 38% of patients reported pain during injection, the median pain score was 0 (none), and these patients reported the pain intensity to be mild to moderate. In Group 3, the dilution of rocuronium to 0.5 mg/mL with 0.9% NaCl completely eliminated the pain on injection (Table 3).
The osmolality of rocuronium 10 mg/mL was 308 mOsm/kg H2O. The osmolalities of rocuronium 1 and 0.5 mg/mL were 306 and 305 mOsm/kg H2O, respectively. The pH of rocuronium 10 mg/mL was 4.14. The pH values of rocuronium 1 and 0.5 mg/mL were 4.15 and 4.18, respectively. The pH values and osmolalities of all study solutions were not significantly different.
|
Discussion
|
|---|
Pain is common on injection of rocuronium during the induction of general anesthesia. Incidences of pain-related withdrawal reactions up to 50%–80% have been observed (5,6). The intense pain caused by rocuronium has restricted its use before succinylcholine, and perhaps patients should be asleep before rocuronium is administered (5,6). The pathophysiological mechanisms that lead to this adverse effect are still unclear. Possible explanations include activation of nociceptors by the unphysiological osmolality or pH of the solution or activation by the release of endogenous mediators, such as histamine or bradykinin (4,6). On the basis of the disagreement regarding pathophysiological mechanisms, there is controversy about the prevention of rocuronium injection pain.
Joshi and Whitten (7) demonstrated that pretreatment with 2 mg of IV midazolam and 100 µg of IV fentanyl prevented the pain associated with injection of a defasciculating dose of rocuronium in adults. Ruetsch and Borgeat (8) reported that fentanyl 2 µg/kg was effective in reducing pain on injection of rocuronium. Shevchenko et al. (9) and Moorthy and Dierdorf (3) showed that pain with injection of rocuronium could be attenuated by pretreatment with IV lidocaine. Cheong and Wong (10) evaluated the effect of two different doses of lidocaine on the incidence of injection pain and found that both 10 and 30 mg of IV lidocaine, given before the administration of rocuronium, significantly reduced the incidence and severity of pain on injection of rocuronium and that the larger dose was more effective. Reddy et al. (11) demonstrated that ondansetron was effective in relieving the pain of rocuronium but was not as effective as lidocaine. Memis et al. (12) compared the efficacy of ondansetron, lidocaine, tramadol, and fentanyl in minimizing the pain caused by injection of rocuronium and concluded that all these drugs were effective. They reported that lidocaine was the most effective among those drugs. In another study, Memis et al. (13) compared the efficacy of magnesium sulfate, lidocaine, sodium bicarbonate, and alfentanil in minimizing the pain produced by rocuronium. Of those drugs, they found that magnesium sulfate and sodium bicarbonate were effective. Chiarella et al. (15) demonstrated that mixing rocuronium 10 mg with sodium bicarbonate 8.4% reduced pain during IV administration of rocuronium. In all these studies, either a pretreatment drug was given before IV administration of rocuronium or rocuronium was mixed with different drugs. There are potential problems with both mixing different drugs and increasing the number of drugs administered to a patient. If a drug is coadministered, then the product is being administered outside its license, and the anesthesiologist assumes some of the responsibilities of the manufacturer. In addition, the more drugs administered to a patient, the more likely an adverse drug effect will occur (14).
Peripheral veins are innervated with polymodal nociceptors that mediate the response to the injection of certain anesthetics that cause pain (16). In the case of propofol, the most effective clinical strategy has always been to inject the propofol into a large vein, which reduces the pain from 30% to 40% when the injection is made into the dorsum of the hand to 3% or less if it is given in the antecubital fossa (17). In a similar observational study for rocuronium, Dalgleish (14) demonstrated that the use of a large vein in the antecubital fossa is likely to minimize the discomfort caused to the patient. Klement and Arndt (18) suggested that pain on injection can probably be avoided by diluting drug formulations. When these data were taken into consideration, it was thought that dilution with 0.9% NaCl would be an important strategy in decreasing or preventing injection pain due to rocuronium. The administration of muscle relaxants before an anesthetic can be unpleasant for the patient. However, in our study, no patient reported side effects such as heavy eyelids, blurred vision, or difficulty in swallowing and breathing. These adverse effects may have been masked by the anesthetics given 10 seconds after rocuronium injection.
Our randomized, double-blinded study showed that the dilution of rocuronium to 1 mg/mL significantly reduced the incidence and intensity of pain compared with rocuronium 10 mg/mL. Moreover, dilution of rocuronium to 0.5 mg/mL with 0.9% NaCl completely prevented the pain associated with IV rocuronium injection.
Solutions with unphysiological osmolality and pH evoke pain on injection into veins at the dorsum of the hand of humans (18). In this study, we found that dilution of rocuronium 10 mg/mL to 1 or 0.5 mg/mL with 0.9% NaCl did not produce significant changes in the osmolality or pH of the drug. The osmolality of rocuronium 10 mg/mL was 308 mOsm/kg H2O. This result was almost normal. Therefore, it seems unlikely that osmolality is responsible for the pain on IV rocuronium injection. Borgeat and Kwiatkowski (6) showed that patients receiving IV saline adjusted to pH 4 reported no pain, whereas patients receiving rocuronium 10 mg/mL did. Our findings are in agreement with these authors that the pH of the drug is not the major cause of pain during IV administration.
Because 2.5–5 mg of rocuronium is required for an adult patient weighing 40–90 kg for attenuation of succinylcholine’s adverse effects, a syringe of 10 mL and a small amount of normal saline is sufficient for diluting rocuronium 0.5 mg/mL. The absence of an additional drug in this method will not cause a modification in drug formulation, will not increase the possibility of side effects, and will not cause unnecessary cost.
In conclusion, 1) in awake patients it seems unlikely that osmolality and pH are responsible for the pain on IV rocuronium injection; 2) with small doses before succinylcholine or nondepolarizing agent administration (0.06 mg/kg), dilution of rocuronium to 1 mg/mL with 0.9% NaCl significantly reduces the incidence and intensity of pain on injection; and 3) dilution of rocuronium to 0.5 mg/mL with 0.9% NaCl is a simple and cost-effective strategy for preventing pain during IV rocuronium injection.
|
References
|
|---|
- Savarese JJ, Caldwell JE, Lien CA, Miller RD. Pharmacology of muscle relaxants and their antagonists. In: Miller RD, ed. Anesthesia. Philadelphia: Churchill Livingstone, 2000: 412–90.
- Martin 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: 521–5.[Abstract/Free Full Text]
- Moorthy SS, Dierdorf SF. Pain on injection of rocuronium bromide. Anesth Analg 1995; 80: 1067.
- Lockey D, Coleman P. Pain during injection of rocuronium bromide. Anaesthesia 1995; 50: 474.
- Steegers MA, Robertson EN. Pain on injection of rocuronium bromide. Anesth Analg 1996; 83: 193–205.
- Borgeat A, Kwiatkowski D. Spontaneous movements associated with rocuronium: is pain on injection the cause? Br J Anaesth 1997; 79: 382–3.[Abstract/Free Full Text]
- Joshi GP, Whitten CW. Pain on injection of rocuronium bromide. Anesth Analg 1997; 84: 228–36.
- Ruetsch YA, Borgeat A. Withdrawal movements associated with the injection of rocuronium. Anesth Analg 2000; 90: 227–8.[Free Full Text]
- 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: 7446–8.
- Cheong KF, Wong WH. Pain on injection of rocuronium: influence of two doses of lidocaine pretreatment. Br J Anaesth 2000; 84: 106–7.[Abstract/Free Full Text]
- Reddy MS, Chen FG, Ng HP. Effect of ondansetron pretreatment on pain after rocuronium and propofol injection: a randomised, double-blind controlled comparison with lidocaine. Anaesthesia 2001; 56: 879–905.[ISI][Medline]
- Memis D, Turan A, Karamanl
oglu B, et al. The prevention of pain from injection of rocuronium by ondansetron, lidocaine, tramadol and fentanyl. Anesth Analg 2002; 94: 1517–20.[Abstract/Free Full Text]
- Memis D, Turan A, Karamanloglu B, et al. The prevention of pain from injection of rocuronium by magnesium sulphate, lignocaine, sodium bicarbonate and alfentanil. Anaesth Intensive Care 2003; 31: 277–81.[ISI][Medline]
- Dalgleish DJ. Drugs which cause pain on intravenous injection. Anaesthesia 2000; 55: 828–9.
- Chiarella AB, Jolly DT, Huston CM, et al. Comparison of four strategies to reduce the pain associated with intravenous administration of rocuronium. Br J Anaesth 2003; 90: 377–9.[Abstract/Free Full Text]
- Arndt JO, Klement W. Pain evoked by polymodal stimulation of hand veins in humans. J Physiol 1991; 440: 467–78.[Abstract/Free Full Text]
- Tan CH, Onsiong MK. Pain on injection of propofol. Anaesthesia 1998; 53: 468–76.[ISI][Medline]
- Klement W, Arndt JO. Pain on intravenous injection of some anaesthetic agents is evoked by the unphysiological osmolality or pH of their formulations. Br J Anaesth 1991; 66: 189–95.[Abstract/Free Full Text]
Accepted for publication April 5, 2004.
This article has been cited by other articles:
|
|
|
|
 
J. Y. Kim, J. Y. Kim, Y. B. Kim, and H. J. Kwak
Pretreatment with remifentanil to prevent withdrawal after rocuronium in children
Br. J. Anaesth.,
January 1, 2007;
98(1):
120 - 123.
[Abstract]
[Full Text]
[PDF]
|
|
|
Top
Abstract
Introduction
