Abstract
Objective
Several drugs have been used to prevent or attenuate succinylcholine- induced muscle fasciculations. There are possible advantages to succinylcholine pretreatment. We designed the present study to compare the effectiveness of atracurium versus “mini-dose” (5 mg) succinylcholine pretreatment for the prevention of muscle fasciculations.
Methods
Under standard monitoring, 79 patients were randomly assigned to three groups after premedication: Group 1 (n = 26) received normal saline as a placebo, Group 2 (n = 27) received 0.03 mg/kg atracurium, and Group 3 (n = 26) received 5 mg succinylcholine. Thiopental (4 mg/kg) was administered intravenously 90 seconds after pretreatment, followed by intravenous administration of 1.5 mg/kg succinylcholine. An anesthesiologist graded fasciculations based on a four-point scale, from 0 (none) to 3 (severe). All patients were evaluated on the first postoperative day for the presence of postoperative myalgia (POM), the severity of which was graded on a four-point scale, from 0 = no myalgia to 3 = generalized, severe discomfort.
Results
There were no statistical differences among the three groups with respect to sex, weight or age. In Group 1, 3.8% of the patients showed no fasciculations, while 30.8% had mild, 53.8% had moderate and 11.5% had vigorous fasciculations. In Group 2, fasciculations were absent in 74.1% of the patients, while 25.9% of the patients had mild fasciculations. In Group 3, 23.1% patients had no fasciculations, while 42.3%, 30.8% and 3.8% of the patients showed mild, moderate and vigorous fasciculations, respectively, with succinylcholine pretreatment. There was no difference in the presence or severity of myalgia between Groups 1 and 3. Furthermore, the presence of fasciculations was not correlated with POM in Groups 1 and 3, but a significant correlation was found in Group 2.
Conclusion
Our results showed that the incidence and severity of fasciculations were significantly decreased by atracurium pretreatment but not by pretreatment with succinylcholine or placebo (p<0.0001 and p=0.0003 respectively). However, atracurium did not exert significant effects on POM.
Keywords
atracurium; fasciculation; muscles; pain; succinylcholine;
1. Introduction
Fasciculations during rapid-sequence intubation may lead to increased intracranial pressure and emesis with aspiration. Non-depolarizing neuromuscular blocking (NDMB) drugs are useful in rapid-sequence intubation before succinyl choline administration.1 Several methods have been used to prevent or re-duce the incidence of succinylcholine-induced mus-cle fasciculations, including pretreatment with lidocaine,2 diazepam3 or diphenylhydantion,4 and subparalyzing doses of non-depolarizing muscle relaxants5−10 or succinylcholine.1,11−13
Previous studies have compared the effect of atracurium with that of the defasciculating drug d-tubocurarine.5,14 However, the effectiveness of atracurium pretreatment in preventing succinyl-choline-induced muscle fasciculations has not been compared with that of “mini-dose” succinylcho-line. Therefore, we designed the present study to compare the effectiveness of atracurium with mini-dose succinylcholine in preventing succinyl-choline-induced muscle fasciculations.
2. Methods
2.1. Patients
After approval from our institutional review board and obtaining informed consent from the patients, 79 patients (males and females) aged 15−70 with American Society of Anesthesiologists physical status I and II, who were scheduled for inpatient surgery under endotracheal general anesthesia were enrolled in this study. Exclusion criteria in-cluded aminoglycosides injection, body mass index > 25 kg/m2, cardiovascular, renal, neuromuscular or hepatic disease, pregnancy, suspected difficult tra-cheal intubation, increased intraocular or intra-cranial pressure, malignant hyperthermia, atyp ical plasma cholin esterase, hyperkalemia, hypertension, or treatment with any drug having muscle relaxant properties.
2.2. Treatments
Under standard monitoring, patients were premed-icated with 1 mg of midazolam and 2 μg/kg of fen-tanyl. The patients were then randomly assigned to one of the three groups:
• Group 1 (n = 26): pretreatment with normal sa-line (NS);
• Group 2 (n = 27): pretreatment with 0.03 mg/kg atracurium;
• Group 3 (n = 26): pretreatment with 5 mg/kg suc-cinylcholine.
The drugs were prepared in a standardized vol-ume in 2 mL syringes and administered in a double-blind manner. After administration of the allocated treatment, the patient was asked to elevate his/her head and protrude the tongue to reveal muscle weakness, and checked for signs of restlessness. Thiopental (4 mg/kg) was administered intrave-nously 90 seconds after pretreatment to induce anesthesia, followed by the intravenous adminis-tration of 1.5 mg/kg succinylcholine for intubation.
2.3. Assessment of fasciculations and myalgia
Fasciculations were graded by an anesthesiologist on the following four-point scale:
• 0 = no fasciculations;
• 1 = mild, fine fasciculations of the eyes, neck, face or fingers, without limb movement;
• 2 = moderate fasciculations occurring at more than two sites, or obvious limb movement;
• 3 = vigorous or severe, sustained and widespread fasciculations in the trunk and limbs.
All patients were reviewed on the first postop-erative day by a single interviewer blinded to the treatment. Patients were evaluated for postopera-tive myalgia (POM), irrespective of the site of op-eration, and the severity of POM was assessed using a four-point scale:
• 0 = no myalgia;
• 1 = minor pain limited to one area of the body;
• 2 = muscle pain or stiffness noticed spontaneously by the patient, which may have required analge-sic therapy;
• 3 = generalized, severe, or incapacitating dis-comfort.
2.4. Statistical analysis
Age and weight were analyzed using the Kruskal-Wallis test. Sex, severity and the presence of fas-ciculations and myalgia were analyzed by χ2 tests and the significance between groups was evaluated using χ2 or Fischer’s exact tests, as appropriate.
Bivariate correlations between the fascicula-tion score and POM were determined and Pearson’s correlation coefficients were determined. SPSS software version 12.0 (SPSS Inc., Chicago, IL, USA) was used for all analyses. Values of p < 0.05 were considered statistically significant.
3. Results
Data were collected intraoperatively from 79 pa-tients and all patients were followed-up. There were no statistical differences among the three groups in terms of sex, weight or age (Table 1).
In Group 1, 3.8% of the patients showed no fas-ciculations, while 30.8%, 53.8% and 11.5% of the patients had mild, moderate and vigorous fascicu-lations, respectively. Fasciculations were absent in 74.1% of patients in Group 2, while the remainder (25.9%) had mild fasciculations only after atracu-rium pretreatment. In Group 3, 23.1% of the pa-tients had no fasciculations, while 42.3%, 30.8% and 3.8% of the patients had mild, moderate and vigorous fasciculations, respectively, after succi-nylcholine pretreatment.
The severity of fasciculations was significantly lower with atracurium pretreatment compared with NS and succinylcholine pretreatment (p < 0.0001). Furthermore, in Group 1, almost all patients had fasciculations, whereas fasciculations were absent in 74.1% of patients in Group 2 and 23.1% of pa-tients in Group 3. Therefore, atracurium pretreat-ment significantly decreased the incidence of fasciculations as compared with NS and succinyl-choline (p < 0.0001 and p = 0.0003 respectively; Table 2).
There was no difference in the presence or sever-ity of myalgia between the three groups, irrespec-tive of the pretreatment used (Table 2). Although there was no significant correlation between fas-ciculations and POM in Groups 1 and 3, a signifi-cant correlation was found in Group 2 (Table 3).
4. Discussion
This study revealed that the incidence and severity of fasciculations were significantly decreased with atracurium pretreatment, compared with succinyl-choline or NS pretreatment, although atracurium did not exert significant effects on POM.
The effectiveness of subparalyzing doses of suc-cinylcholine and NDMB drugs in reducing the in-cidence or fasciculations or preventing them has been shown to be drug-specific and is dependent on the interval between pretreatment and the ad-ministration of the main dose of succinylcholine.15
Fasciculations are caused by antidromically conducted axonal depolarizations initiated by suc-cinylcholine binding to prejunctional nicotinic cholinergic receptors.4 The likelihood of blocking succinylcholine-induced muscle fasciculations is greatest with d-tubocurarine, followed by atracu-rium, pancuronium, and vecuronium.15 It has been suggested that the reduced incidence of fascicu-lation with d-tubocurarine and atracurium is due to the greater affinity of these drugs for prejunc-tional cholinergic receptors compared with pan-curonium and vecuronium.15,16 This may reflect the differences in drug potency, which influences re-ceptor binding and the rate of onset of action.17 The rate of NDMB onset at the postjunctional re-ceptor is inversely related to drug potency,18 and a similar phenomenon may exist at the prejunctional receptor.15
Pinchak et al15 have reported that the interval needed for atracurium to prevent succinylcholine-induced muscle fasciculations in 90% of patients is 3.26 minutes.15 However, applying this interval for succinylcholine pretreatment would result in sig-nificant hydrolysis of the drug by plasma cholineste-rase. Based on this concept, we used a 1.5-minute interval in this study, to ensure the mini-dose suc-cinylcholine elicited its peak effect before its hy-drolysis. However, we also know that atracurium does not reach its peak effect in this interval, but double-blind comparisons of mini-dose succinyl-choline with NDMB drugs for the prevention of suc-cinylcholine-induced muscle fasciculations should include standardized intervals for all drugs, begin-ning at 90 seconds, to accurately evaluate the efficacy of these approaches.19
In contrast to the findings reported by Harvey et al,19 our study revealed a significant decrease in the incidence and severity of fasciculations with succinylcholine pretreatment compared with NS, which was predictable based on the above assumptions.
There are several advantages to succinylcholine pretreatment. First, pretreatment with NDMBs can attenuate the effect of succinylcholine and con-sequent deterioration during intubation. However, this problem can be overcome by increasing the dose of succinylcholine to 1.5 mg/kg.20−24 Although succinylcholine pretreatment may not influence the patient’s status during intubation, further studies are needed on whether this is really the case. Furthermore, we must also consider that the inci-dence and severity of fasciculations were signifi-cantly lower in patients pretreated with atracurium than in those pretreated with succinylcholine. In terms of the dosing interval of 3.26 minutes for atracurium, it may be that this time interval may further decrease the incidence of fasciculations, although studies are needed to confirm this.
Our results support those of earlier studies, that pretreatment with an NDMB agent, atracurium, did not decrease the incidence of myalgia after major abdominal surgery.19,25 Furthermore, a weak cor-relation between visible fasciculations and myal-gia was only found in Group 2, which was consistent with earlier studies.14,19,26 However, we did not limit our study population to those undergoing a specific surgical procedure, which may have influ-enced the results.
In summary, our study indicates that the inci-dence and severity of fasciculations were signifi-cantly reduced by atracurium pretreatment, as compared with pretreatment with NS or mini-dose succinylcholine, although atracurium exerted no effects on POM.
Acknowledgments
The authors thank Amir Alam Hospital Research Center.