Spontaneous movements, local reactions and pain on injection of rocuronium. A comparison between female and male patients

BACKGROUND: We investigated the incidence of withdrawal, local reactions and pain on injection of rocuronium in 120 adult ASA I-II patients undergoing general anaesthesia (group A: 60 male patients, group B: 60 female patients). METHODS: After induction of anaesthesia with propofol and remifentanil, rocuronium 0.6 mg kg(-1) was injected in a separate intravenous cannula on the opposite arm. The patient's response to the injection of rocuronium was graded using a four-point scale. The appearance of local signs (i.e. erythema, venous sequelae) on the arm where rocuronium had been injected was recorded at the end of the injection as well as 1 h and 24 h after recovery from anaesthesia. Moreover, patients were asked 24 h after recovery from anaesthesia whether they had recall of pain or movements in this arm during induction of anaesthesia. RESULTS: In 26 of the 120 patients (22%) included, withdrawal reactions after injection of rocuronium were observed. Of these 26 patients, 16 (13%) had severe movements. The overall incidence of withdrawal reactions after rocuronium as well as the incidence of severe reactions was significantly higher in female patients compared to male patients (overall incidence: 18 females (30%) vs. 8 males (13%), P<0.05; severe reaction: 13 females (22%) vs. 3 males (5%), P<0.05). No local reactions were observed and no patient remembered any pain or movements during induction of anaesthesia. CONCLUSION: The incidence and the degree of withdrawal reactions in response to the injection of rocuronium were significantly higher in women than in men. This was not associated with adverse clinical consequences for the patient's outcome.     

罗库溴铵静脉注药痛

罗库溴铵静脉注射时有些病人会诉说注药局部疼痛或引起肢体不自主抽动.发生机制可能与肌松药pH值偏低、激肽原级联反应以及罗库溴铵刺激C神经纤维和肥大细胞反应有关.预先静脉注射利多卡因、芬太尼类药物、枢复宁、右旋美托咪啶、阈下剂量氯胺酮或8.4%碳酸氢钠能明显降低罗库溴铵诱发注药局部疼痛的程度和发生率.     

Comparison of four strategies to reduce the pain associated with intravenous administration of rocuronium

Background. I.V. rocuronium produces intense discomfort at thesite of injection in conscious patients. Four strategies toreduce or prevent this discomfort were studied. Methods. Two hundred and fifty adult patients, ASA I–III,were randomized into five groups of 50 patients in a blinded,prospective study. The control group received rocuronium 10 mgalone. For the remaining four groups, rocuronium 10 mgwas mixed with sodium bicarbonate 8.4% 2 ml, fentanyl 100 µg,lidocaine 2% or normal saline. The pH and osmolality of allmixtures were measured. Patient data were analysed using ordinallogistic regression. Osmolality and pH data were analysed usingthe Kruskal–Wallis test with Dunn’s multiple comparisontest. Results. When compared with rocuronium alone, only the additionof saline failed to significantly reduce the pain reported bypatients. The addition of fentanyl reduced the complaint ofpain by 1.9 times (P<0.049) and the addition of lidocaine2% reduced it by 3.6 times (P<0.0001). Sodium bicarbonate8.4% 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. administrationof a small dose of rocuronium. Br J Anaesth 2003; 90: 377–9     

Rocuronium-induced withdrawal movements associated with different Rocuronium injection method

Objectives: One hundred and twenty patients (3–15 years old) were randomly enrolled (four groups: each group = 30 patients) in the study. Aim: The aim of this study was to compare the incidence and intensity of rocuronium‐induced withdrawal movements in children injected with a typical intravenous bolus injection of rocuronium or with an infusion injection of rocuronium. Background: Intravenous bolus injection of rocuronium produces pain and withdrawal movement. Methods: Immediately after loss of consciousness by thiopental sodium (5 mg·kg^?1), 0.6 mg·kg^?1 (B0.6, I0.6) or 0.9 mg·kg^?1 rocuronium (B0.9, I0.9) was injected by different method, either a bolus injection over 5 s (B0.6, B0.9) or an infusion injection lasting for 1 min (I0.6, I0.9). The withdrawal movement of the patients to the injection of rocuronium was assessed (four‐grade score: 0–3). Intubating condition was assessed. Rocuronium‐induced muscle relaxation time was measured by single twitch stimulation fade out. Results: The incidence (group B: 100%, group I: 33.3%) and the intensity of the withdrawal movements were significantly lower in the infusion groups compared with the bolus groups (P < 0.05). The intubating conditions for all groups were clinically acceptable (good to excellent). There was no significant difference in the muscle relaxation time between the different injection groups (I0.6; 105.6 ± 7.7 vs B0.6; 114.6 ± 8.0, I0.9; 69.2 ± 3.6 vs B0.9; 73.4 ± 1/0). Conclusions: The infusion injection of rocuronium for tracheal intubation significantly reduced the incidence and intensity of withdrawal movement on injection of rocuronium, and it neither delays the onset of muscle relaxation nor deteriorates the intubating condition.     

芬太尼预防罗库溴铵注药痛的研究

目的观察罗库溴铵注药痛的发生率、致痛程度以及预先注射芬太尼的预防效果。方法拟行全身麻醉的成年手术患者175例。麻醉诱导时用限时法给予罗库溴铵。按给予罗库溴铵前的处理方法将患者随机分成七组,每组25例。～Ⅳ组将左上臂包裹的气压止血带加压至70mmHg以阻断静脉回流。于左手背静脉注射预处理药物：Ⅰ组为生理盐水3ml;Ⅱ～Ⅳ组为芬太尼2μg／kg,速度3ml／10s。Ⅰ组和Ⅱ组注药后30S松开止血带,Ⅲ组和Ⅳ组分别于注药后60S和120S松开止血带,立即在该静脉10S内注入罗库溴铵0．6mg／kg。Ⅴ～Ⅶ组不用止血带,以3ml／10s速度注入芬太尼2μg／kg;Ⅴ组、Ⅵ组和Ⅶ组分别在注药后30、60S和120S后于该静脉10S内注入罗库溴铵0．6mg／kg。观察患者在注射罗库溴铵时的反应,并对各种反应评估分级。结果罗库溴铵注药痛发生率Ⅰ组达92％,明显高于Ⅳ组（64％）和Ⅶ组（52％）（P〈0．01）;Ⅰ组中、重度注药痛发生率达56％,而Ⅳ组和Ⅶ组均为轻度疼痛。Ⅳ组与Ⅶ组注药痛组间比较差异无统计学意义。Ⅱ组和Ⅲ组注药痛发生率均为84％,V组和Ⅵ组分别为96％和88％,和Ⅰ组相似。Ⅵ组中、重度注药痛发生率（12％）比Ⅰ组明显减少（P〈o、05）。结论麻醉诱导时预先静脉注射芬太尼2μg／kg,不论是否用止血带阻断静脉回流,120S后再注入罗库溴铵时,均能有效降低罗库溴铵注药痛的发生率和致痛程度。     

Prevention of withdrawal movement associated with injection of rocuronium in children: comparison of remifentanil, alfentanil and fentanyl

BACKGROUND: We compared the efficacy of remifentanil, alfentanil and fentanyl in reducing withdrawal movement associated with the injection of rocuronium in children. METHODS: In total, 164 ASA physical status I or II pediatric patients, aged 1-14 years, were randomly assigned to four treatment groups: group C received saline; group R, remifentanil 1 microg/kg; group A, alfentanil 10 micro/kg; and group F, fentanyl 2 microg/kg. Treatments were injected over 30 s, followed by thiopental 5 mg/kg. At 90 s after the start of the study drug injection, rocuronium 0.6 mg/kg was injected over 10 s. The patient's response to the injection of rocuronium was graded on a four-point scale in a double-blinded manner. RESULTS: The incidence of withdrawal movement was 89.5% in group C, 70.3% in group F, 36.3% in group A and 7.2% in group R. The incidence of generalized movement (grade 4) was 86.9% in group C, 58.5% in group F, 15.9% in group A and 2.4% in group R. CONCLUSION: Remifentanil, alfentanil and fentanyl all reduced the incidence of withdrawal movement when administered 90 s before the injection of rocuronium compared with saline. Remifentanil was the most effective, followed by alfentanil. Fentanyl was less effective but significantly different from the saline in reducing withdrawal movement in children.     

Effect of ondansetron pretreatment on pain after rocuronium and propofol injection: a randomised, double-blind controlled comparison with lidocaine

In a randomised, controlled, double-blinded trial to study the effect of ondansetron pretreatment on the pain produced after intravenous injection of rocuronium and propofol in comparison with lidocaine, 60 patients were randomly assigned to one of three groups. Group 1 received 5 ml of intravenous 0.9% sodium chloride solution pretreatment, group 2 received ondansetron 4 mg (2 mg.ml-1 solution) diluted into a 5-ml solution, and group 3 received 50 mg lidocaine (5 ml 1% solution); this was followed 1 min later by rocuronium and propofol. Pain was reduced significantly in the ondansetron and lidocaine groups (p < 0.0001) compared with placebo, and significantly better with lidocaine than with ondansetron (p = 0.02). We conclude that ondansetron is effective in relieving the pain of rocuronium but is not as effective as lidocaine.     

Rapid injection of rocuronium reduces withdrawal movement on injection

Study ObjectiveTo test whether rapid injection of rocuronium reduces withdrawal movement on injection.DesignRandomized, prospective trial.SettingOperating room in a university hospital.Patients150 ASA physical status I and II patients aged 18 to 60 years, undergoing general anesthesia.InterventionsPatients were randomized to three groups. After undergoing anesthesia induction with thiopental sodium, then 5 seconds later receiving a rubber tourniquet applied to the mid-forearm to stop intravenous (IV) flow by gravity, the pretreatment drug was injected. The tourniquet was held for 15 seconds then released, and 1.0 mg/kg of 1% rocuronium was injected IV. Group C patients (n = 50) were pretreated with 0.1 mL/kg of 0.9% NaCl and then injected with rocuronium slowly within 10 seconds. Group L patients (n = 50) were pretreated with 0.1 mL/kg of preservative-free 1% lidocaine and then injected with rocuronium slowly within 10 seconds. Group R patients (n = 50) were pretreated with 0.1 mL/kg of 0.9% NaCl and then rapidly injected with rocuronium within approximately one second (as quickly as possible).MeasurementsAfter injection of the patient with the study drug, a single anesthesiologist with no knowledge of the study protocol graded each patient's response as follows: 0 = no response; 1 = mild movement limited to the wrist only; 2 = moderate movement involving the elbow and shoulder; and 3 = severe movement involving more than one extremity.Main ResultsGroup C had the most intense and frequent withdrawal response. The frequency and intensity of withdrawal movement was significantly less in Groups L and R than Group C. No significant difference in withdrawal response between Groups L and R was noted.ConclusionsWithdrawal response can be significantly reduced for rocuronium injection without lidocaine pretreatment, simply through rapid injection.     

Pretreatment with remifentanil to prevent withdrawal after rocuronium in children

Background. Pain from rocuronium injection is a common side-effectreported to occur in 50–80% of the patients. This randomized,double-blind, placebo-controlled study was designed to evaluatethe efficacy of pretreatment with i.v. remifentanil on preventionof withdrawal response during rocuronium injection in paediatricpatients. Methods. After obtaining parental consents, 70 paediatric patientswere randomly allocated into two groups to receive either i.v.remifentanil 1 µg kg^–1 (remifentanil group, n=35)or i.v. saline 5 ml (saline group, n=35). Anaesthesia was inducedwith thiopental sodium 2.5% (5 mg kg^–1) and the test drugwas injected over 30 s. One minute after the test drug injection,rocuronium 1% (0.6 mg kg^–1) was injected over 5 s andthe response was recorded. Mean arterial pressure (MAP) andheart rate were recorded on arrival in the operating theatre,before and 1 min after the tracheal intubation. Results. The overall incidence of withdrawal movements was significantlyhigher in the saline group (33 patients; 94%) than that in theremifentanil group (8 patients; 23%) (P<0.001). No patientin the remifentanil group showed generalized movement, whereas51% of patients in the saline group did. Remifentanil preventedsignificant increase in MAP after intubation. Conclusion. This study demonstrated that pretreatment with remifentanil1 µg kg^–1 provided a safe and simple method forreducing the incidence of rocuronium-associated withdrawal movementwith haemodynamic stability in children.     

Spontaneous movements associated with rocuronium: is pain on injection the cause?

Spontaneous movements are sometimes observed of the arm into which rocuronium is administered. In order to assess a possible relationship between these movements and pain, we injected in 10 awake, ASA I patients, in a double-blind manner, both rocuronium 1 ml (10 mg) and 0.9% NaCI 1 ml (placebo), with a 30-s interval in between. None of the patients receiving placebo complained of pain, but eight of 10 patients reported a strong burning pain during injection of rocuronium with brisk flexion of the elbow and wrist, similar to those observed in patients after induction of anaesthesia. A second injection of rocuronium did not produce such pain and no movements were observed. We conclude that injection of rocuronium is associated with severe, burning pain of short duration, responsible for the spontaneous movements in the arm observed after induction of anaesthesia.      

Women report more pain on injection of a precurarization dose of rocuronium: a randomized, prospective, placebo-controlled trial

BACKGROUND: The purpose of this study was to investigate whether gender influences the perception of pain on injection of rocuronium. METHODS: In this prospective, placebo-controlled trial 120 patients were randomized into four groups to receive rocuronium 0.03 mg kg(-1) (40 female and 40 male patients) or saline (20 female and 20 male patients). The incidence and severity of the injection pain after administration of the study drug was compared between female and male patients using a numerical rating scale (0-10). Signs of local irritation, i.e. erythema and thrombophlebitis, were assessed up to 48 h after surgery. RESULTS: In 26 (32.5%) of the 80 patients receiving rocuronium, pain on injection was observed. This occurred significantly more frequently in the female compared with male patients: 18 (45%) vs. eight (20%), respectively (P = 0.032). The severity was more pronounced in the women than in the men (P = 0.020). The incidence of the rocuronium-associated pain was significantly increased compared with the Saline groups (P < 0.001). After surgery no patient complained of any residual pain and no local signs were observed in any patient during the study period. CONCLUSIONS: Women experienced more pain on injection of rocuronium than men, moreover this is an additional evidence for gender-related differences in pain perception. When rocuronium is used as a precurarization agent, an analgesic pretreatment (e.g. opioids) should be considered, especially for female patients.     

Evaluation of intubating conditions with rocuronium and either propofol or etomidate for rapid sequence induction

We have assessed the effect of two induction agents on tracheal intubating conditions after rocuronium 0.6 mgkg⁻¹ in unpremedicated patients undergoing simulated rapid sequence induction. Following pre-oxygenation, anaesthesia was induced with propofol up to 2.5 mgkg⁻¹ ( n  = 35) or etomidate 0.3 mgkg⁻¹ ( n  = 36), and further increments as required. After loss of verbal contact, cricoid pressure was applied and rocuronium was injected. Laryngoscopy was performed at 45 s and intubation attempted at 60 s after rocuronium had been given. Ninety-four per cent of patients in the propofol group had clinically acceptable (good or excellent) intubating conditions compared to only 75% in the etomidate group (p = 0.025). Owing to coughing, one patient in the etomidate group could not be intubated on the first attempt. A greater pressor response also followed intubation after induction with etomidate. We conclude that etomidate and rocuronium alone cannot be recommended for intubation at 60 s under rapid sequence induction conditions.     

Effect of prior administration of cold saline on pain during propofol injection

A single-blind, randomised, controlled study was undertaken to compare the efficacy of three methods of preventing pain during injection of propofol on induction of anaesthesia. Patients were allocated randomly to receive unmodified propofol, propofol with 0.05% lignocaine, propofol at 4 degrees C and unmodified propofol preceded by 10 ml of 0.9% saline at 4 degrees C. Prior injection of cold saline reduced the incidence of pain and discomfort significantly (22%) compared with unmodified propofol (75%; p less than 0.005) and was similar to that after cold propofol (33%) and propofol with lignocaine (44%). There was no significant difference between the treatment groups.     

The influence of induction technique on intubating conditions 1 min after rocuronium administration: a comparison of a propofol-ephedrine combination and propofol

We conducted a double blind, prospective, controlled trial comparing intubating conditions after induction with a propofol-ephedrine combination or propofol alone, followed by rocuronium. One hundred adult patients were randomly assigned to receive either propofol 2.5 mg x kg(-1) and ephedrine 15 mg in combination or propofol 2.5 mg x kg(-1) given over 30 s, followed by rocuronium 0.6 mg x kg(-1) given over 5 s. Tracheal intubation was performed 1 min later. Jaw relaxation, vocal cord position and diaphragmatic response were used to assess intubation conditions. Tracheal intubation was successful and acceptable in all patients. There was a significantly higher proportion of intubating conditions graded as 'excellent' in the propofol-ephedrine group (84%) than in the propofol group (32%) (p < 0.0001). Vocal cord position and response to intubation were significantly better in the propofol-ephedrine group, although jaw relaxation was similar. Mean arterial pressure was maintained at pre-induction levels in the propofol-ephedrine group. In conclusion, induction with propofol and ephedrine in combination provided significantly better intubating conditions than propofol alone, when followed by rocuronium.     

Target controlled infusion of rocuronium: analysis of effect data to select a pharmacokinetic model

Background. We aimed to evaluate whether area under the curve(AUC) analysis of pharmacodynamic data can be used to comparepharmacokinetic models taken from the literature, during a targetcontrolled infusion (TCI) of rocuronium. Methods. Seventy-two patients scheduled for orthopaedic surgeryreceived a TCI of rocuronium (Stanpump) based on one of fourpharmacokinetic models: those described by Szenohradszky, Alvarez-Gomez,Wierda, and Cooper. The resulting theoretical plasma concentrationversus time curve was calculated for all patients based on allfour pharmacokinetic models. Predicted effect versus time curveswere calculated following the pharmacokinetic–pharmacodynamiclink model (Sheiner and colleagues). Neuromuscular block wasevaluated acceleromyographically. The difference between thearea under the observed effect (AUC_OE) and predicted effect(AUC_PE) versus time curves was used for comparison. Results. AUC_PE differed significantly from AUC_OE in the Szenohradszkyand Alvarez-Gomez models, both with the reference link-pharmacodynamicdata and with altered link-pharmacodynamic variables. AUC_PEand AUC_OE were comparable for the Wierda and Cooper models.The mean AUC_OE was 25.1 (SD 11.9)% blockxh. AUC_PE–AUC_OEwas significantly larger in the Szenohradszky model when comparedwith all other pharmacokinetic models. This difference remainedwhen link or pharmacodynamic variables were modified. The smallestAUC_PE–AUC_OE difference was found with the Wierda model. Conclusion. It was possible to use AUC analysis for identificationof the pharmacokinetic model that best predicted the pharmacodynamiccharacteristics of our patients. Br J Anaesth 2003; 90: 183–8     

Reversal of rocuronium with edrophonium during propofol versus sevoflurane anesthesia

BACKGROUND: The use of volatile anesthetics for maintenance of anesthesia can enhance the action of non-depolarizing muscle relaxants and interfere with the reversal of neuromuscular blockade. In this study, we studied the antagonism of rocuronium with edrophonium-atropine during propofol- versus sevoflurane-based anesthesia. METHODS: Following induction of anesthesia with propofol (2-2.5 mg kg(-1), i.v.) and fentanyl (1-2 microg kg(-1) i.v.), rocuronium 0.6 mg kg(-1) i.v. was administered to facilitate tracheal intubation. Patients were then randomized to receive either a propofol infusion (100 microg kg(-1) min(-1)) or sevoflurane (1.0%, end-tidal) in combination with nitrous oxide 66% for maintenance of anesthesia. Neuromuscular blockade was monitored using electromyography at the wrist, and reversed with edrophonium 1.0 mg kg(-1) and atropine 0.015 mg kg(-1) when the first twitch hight (T1) of the train-of-four (TOF) stimulation recovered to 25% of the baseline value. Anesthetic maintenance with propofol or sevoflurane was continued following reversal until a TOF ratio of 0.7 was attained. RESULTS: The clinical duration of action (i.e., time to 25% T1 recovery) was similar during both propofol- (39.3+/-14.6 min) and sevoflurane-based (48.1+/-19.7 min) anesthesia. However, the reversal time from 25% T1 to TOF ratio of 0.7 was significantly longer with sevoflurane [Median 2.8 (range 0.5-18.8) min] compared with propofol [1.5 (0.75-3) min] (P<0.05). CONCLUSIONS: We conclude that the clinical duration of action after a single dose of rocuronium, 0.6 mg kg(-1) i.v., was similar during both propofol- and sevoflurane-based anesthesia. However, the reversal of rocuronium-induced residual blockade was slower and more variable in the presence of sevoflurane.     

Effect of pretreatment with ketorolac on propofol injection pain

BACKGROUND: : Pain on injection is still a major problem with propofol. We performed this study to compare different doses of intravenous (i.v.) ketorolac with and without venous occlusion and its effect on the incidence and the severity of the pain after propofol injection. METHODS: We conducted a prospective, randomized and double-blind study of 180 patients (20-60 years of age.) scheduled to undergo elective surgery. Six groups of patients were generated: group A received normal saline (NS) 2 ml i.v.; groups B, C, D received ketorolac 10 mg in 2 ml NS with venous occlusion (VO) and a subsequent propofol injection at either 30, 60 or 120 s; groups E and F received ketorolac 15 mg and 30 mg in 2 ml NS and propofol was injected after 60 s. The pain perception was assessed during injection of propofol in all patients. RESULT: : The incidence of propofol-associated injection pain was for A: 46.7%; B: 43.4%; C: 23.3%; D:16.7%; E: 20%, and F: 10%. The incidence of pain following propofol injection was reduced by i.v. ketorolac 10 mg with venous occlusion for 120 s. Furthermore, i.v. ketorolac 15 mg and 30 mg but not 10 mg following propofol injection after 60 s without venous occlusion revealed significant pain reduction when compared to saline group. There was no difference in venous sequelae at 7 days postoperatively between the groups. CONCLUSION: Our results suggested that pretreatment with i.v. 15 and 30 mg ketorolac reduces pain following propofol injection. Moreover, pretreatment with i.v. ketorolac 10 mg with venous occlusion for 120 s achieves the same pain relief effect.     

Preventing the withdrawal response associated with rocuronium injection: a comparison of fentanyl with lidocaine

We compared the efficacy of IV fentanyl with IV lidocaine as pretreatment for the prevention of withdrawal response after rocuronium injection. For this prospective, randomized, placebo-controlled, double-blind study we recruited 90 patients aged between 18 and 65 yr, ASA physical status I or II, who had undergone elective surgery requiring general anesthesia and positive pressure ventilation. Patients were randomly allocated to 1 of 3 groups: group F received 2 mL IV fentanyl 50 microg/mL (100 microg), group L received 2 mL of preservative-free lidocaine 2% (40 mg), and group P (placebo) received 2 mL of normal saline. The incidence of withdrawal response after rocuronium was 57%, 30%, and 7% in the placebo, lidocaine, and fentanyl groups, respectively. We found a significant reduction in incidence of withdrawal response in both the fentanyl and lidocaine groups when compared with the placebo group (P < 0.05), with the fentanyl group being most effective (P < 0.05). In conclusion, both fentanyl and lidocaine are effective clinical treatments to alleviate the withdrawal response associated with rocuronium injection, with fentanyl being more effective.     

The cardiovascular effects of naloxone administration after fentanyl anesthesia in hypercapnic patients

Hemodynamic changes and plasma catecholamine levels after naloxone administration were studied in seventeen postoperative patients who received nitrous oxide, oxygen, and fentanyl anesthesia combined with epidural block. Group I consisted of ten postoperative hypercapnic (Pa_{CO 2} = 55.2 ± 2.4 torr) and group II seven postoperative normocapnic patients (Pa_{CO 2} = 38.4 ± 2.1 torr), respectively. In group I, naloxone reversal resulted in significant increases in heart rate (13.5%), mean arterial pressure (46.6%), systemic vascular resistance (32.1%), and rate pressure product (68.8%), whereas mean pulmonary artery pressure and pulmonary vascular resistance were significantly decreased. No significant hemodynamic changes after naloxone administration were observed in group II. There were no significant differences in arterial norepinephrine and epinephrine levels either before or after naloxone administration in the both groups. This study indicates that the postoperative hypercapnia elicits the cardiovascular stimulation after fentanyl reversal by naloxone.(Kishikawa K, Namiki A, Iwasaki H: The cardiovascular effects of naloxone administration after fentanyl anesthesia in hypercapnic patients. J Anesth 3: 48–53, 1989)