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Pakistan Journal of Pharmacology Vol.28, No.1, January 2011, pp.33-41 COMPARATIVE STUDY OF SUCCINYLCHOLINE AND PRECURARIZATION WITH ROCURONIUM ON MUSCULAR EFFECTS IN PATIENTS UNDERGOING SURGERY UNDER GENERAL ANAESTHESIA KULSOOM FARHAT, AKBAR WAHEED, SALMAN BAKHTIAR AND ANWAR KAMAL PASHA* Department of Pharmacology & Therapeutics, Army Medical College, Rawalpindi, Pakistan *Combined Military Hospital, Rawalpindi ABSTRACT: Succinylcholine remains the drug of choice in conditions where rapid paralysis and airway control are priorities. However it is associated with muscular side effects that have an overall incidence ranging from five to 83 percent. The administration of small doses of nondepolarizing muscle relaxants before the administration of succinylcholine has been shown to decrease the incidence and severity of muscular side effects experienced by the patients. This study was aimed at evaluating the efficacy of technique in reducing the muscular side effects of succinylcholine. Sixty healthy adults were enrolled in the study who were scheduled for minor muscle cutting surgeries under general anaesthesia. They were assigned at random to two groups of thirty patients each. They randomly received succinylcholine for intubation and a precurarization dose of rocuronium followed by succinylcholine for intubation. Intraoperative fasciculations and postoperative myalgia were graded and scored. There was a significantly increased incidence of fasciculations and myalgia in the succinylcholine group. In the precurarization group the incidence and severity of fasciculations and myalgia was significantly less as compared to the group which received succinylcholine alone. We found significant correlation between fasciculations and myalgia in the succinylcholine group. Present study concluded that precurarization with rocuronium was effective in reducing the succinylcholine-induced fasciculations and myalgia. Keywords: Succinylcholine, Rocuronium, Fasciculations, Myalgia, Precurarization. INTRODUCTION relaxant, produces profound neuromuscular block with rapid onset but short duration. Patients undergoing general anaesthesia When used in a dose of 0.5 to 1.5 mg/kg, it usually need endotracheal intubation. produces excellent muscle relaxation in 30 Although many relaxing agents can be used seconds and its effects last for 3 to 5 minutes for this purpose; Succinylcholine is still the (Donati and Bevan, 2009). Its short half-life most popularly used agent in our setup. becomes life saving in the event of difficult Despite the recent introduction of short- intubation or failed intubation and rapid acting,nondepolarizing neuromuscular sequence induction in patients with full blockers, succinylcholine with its rapid onset stomach. However the usefulness of of action, short duration of effect, complete succinylcholine is limited by few side effects and predictable paralysis remains the best drug such as muscle fasciculations; postoperative in providing ideal intubating condition for myalgia, increased serum levels of creatinine tracheal intubation (Kato et al., 2007). kinase and potassium, succinyl apnea, Succinylcholine is a depolarizing muscle malignant hyperthermia, raised intraocular Correspondence to: e-mail: firstname.lastname@example.org 34 Comparative study of succinylcholine and precurarization pressure and intracranial pressure. The blocking agent is effective in preventing it fasciculations are a benign side effect of the (Subramaniam et al., 2002). drug, but many anaesthetists prefer to prevent fasciculations. In this respect, a small dose of a Rocuronium is a monoquaternary steroidal nondepolarizing agent, given three to five analogue of vecuronium. It has rapid to minutes before succinylcholine is effective intermediate onset and intermediate duration (Schreiber et al., 2005). When the drug was of action (Bhatti and Parmer, 2009). It requires available, d-tubocurarine 0.05 mg/kg was used 0.45 to 0.9 mg/kg intravenously for intubation for this purpose. Rocuronium is an acceptable and 0.15 mg/kg boluses for maintenance. alternative, as long as appropriate doses 0.09 Rocuronium (0.1 mg/kg) has proved to be to 0.1 mg/kg, or 10 percent of the Effective rapid (90 seconds) and a more effective agent Dose causing on average 95 percent (decreased fasciculations and postoperative suppression of neuromuscular response (ED95) myalgias) for precurarization prior to are given (Donati, 2006). Other drugs such as succinylcholine administration.Various factors diazepam, lidocaine, fentanyl, calcium, influence the efficacy of pretreatment vitamin C, magnesium and dantrolene have including the choice of nondepolarizing also been used to prevent fasciculations. The agents, degree of prejunctional receptor block, results are no better than with nondepolarizing interval between administration of relaxants and they may have undesirable pretreatment agent and succinylcholine and the effects of their own. speed of onset of the nondepolarizing drug. Schrieber et al did a meta analysis of The postoperative myalgia are generalized randomized trial on prevention of aches and pains that commonly occur 24 to 48 succinylcholine-induced fasciculations and hours after succinylcholine administration that myalgia and found that the best prevention of mimic the muscular pains which usually myalgia was with non-steroidal anti- follow violent exercise. It has been postulated inflammatory drugs and with rocuronium. This that the muscle pain is secondary to the study was undertaken with the aim of damage produced in the skeletal muscle by the comparing the efficacy of rocuronium and unsynchronized contraction of adjacent muscle vecuronium for intubation, succinylcholine fibers just before paralysis occurs. Their induced myalgia and the levels of creatine incidence is variable (20 to 80 percent of phosphokinase and urine myoglobin after the patients receiving succinylcholine) and are pretreatment with rocuronium. Our purpose of more common in young, ambulatory patients study was to assess the effects of rocuronium (Mencke et al., 2002). The exact mechanism is pretreatment on succinylcholine-induced not known but stimulation of presynaptic fasciculations and postoperative myalgia. acetylcholine receptors and contraction of intrafusal fibers of muscle spindles may MATERIAL AND METHODS contribute. It has been suggested that the underlying mechanism of muscle damage This study was conducted in the operation associated with administration of theatre of Combined Military Hospital, succinylcholine may involve calcium-induced Rawalpindi from January 2010 to August 2010 phospholipids degradation with release of after approval of the study project by research damaging products of fatty acid metabolism and ethics committee. Written informed (Mcloughin et al., 1988). The intensity of consent was observed from all subjects. It was muscle pains is not always correlated with the a prospective, single blind and randomized intensity of fasciculations, but the methods study including 60 patients who were allocated that prevent fasciculations usually prevent randomly to one of the two groups. Patients in muscle pains. For example, a precurarization group "A" received succinylcholine and group dose of a nondepolarizing neuromuscular “B” received precurarization dose of Farhat et al. 35 Table 1 Grading and scoring system for fasciculations Nil No visible fasciculations 0 Mild Very fine fingertip or facial muscle movements 1 Moderate Minimal fasciculations on trunk and extremities 2 Severe Vigorous fasciculations on trunk and extremities 3 (Yun et al., 2010) Table 2 Grading and scoring system for postoperative myalgia Nil No muscle pain or stiffness 0 Muscle pain or stiffness at one site but not causing disability or Mild 1 limiting activities Muscle pain or stiffness noticed spontaneously by the patient, Moderate 2 possibly requiring analgesic therapy Severe Generalized, severe or incapacitating discomfort 3 (Harvey et al., 1998; Korula et al., 2010) rocuronium followed by succinylcholine. body weight (Naguib et al., 2006). Group "B" There were 30 patients in each group. The two received 0.1 mg/kg rocuronium followed by groups were comparable in respect to age, sex succinylcholine 1.5 mg/kg body weight for and weight. Patients of both sex aged from 18 intubation (Donati and Bevan, 2009). These to 65 years of ASA grade I and II, undergoing drugs were given by an investigator who was elective minor muscle cutting surgeries were not included in rest of the study. Direct included in this study. Patients with no proper laryngoscopy was performed and the patients medical history, intraocular hypertension, were intubated via oral route, 60 seconds after history of malignant hyperthermia, ASA status giving drugs for intubation. Following the III and above, Diabetes mellitus, suspected administration of drugs of intubation, patients difficult intubation patients and major muscle were observed for the presence and severity of cutting surgeries were excluded from this fasciculations by the investigator and recorded study. Preoperative evaluation included on proforma. These fasciculations were graded detailed history, general physical, systemic and scored as a system described in table 1 and upper airway examination. Investigations (Yun et al., 2010). Anaesthesia was including blood complete picture, urine routine maintained with the maintenance doses of the examination, liver function tests, Hepatitis B volatile anaesthetic agent isoflurane and 60 surface Antigen, Anti Hepatitis C Virus, renal percent nitrous oxide in oxygen. All the function tests and electrocardiogram (ECG). patients were visited 24 hours postoperatively These were carried out to exclude liver in the respective wards and were asked about disease, hepatitis B & C, renal disease and the presence and severity of myalgia in a non- heart disease in study subjects. These all leading manner by the investigator (Sen et al., findings were recorded on a pre-clinical and 2003). A questionnaire was given to each and clinical proforma. Routine monitoring was every patient to grade myalgia (Mikat-Steven done after receiving the patient in theater. et al., 2000) using a system described in table Standard anaesthesia technique was employed 2 (Harvey et al., 1998; Korula et al., 2010) and in all patients. Intravenous line was secured data was recorded on proforma. The data was with 18g cannula. Patients were randomized entered in SPSS version 16.0 for analysis. and grouped in group "A" and group "B". Frequency along with percentage was used to Group "A" received succinylcholine 1 mg/kg describe qualitative variables like gender, 36 Comparative study of succinylcholine and precurarization myalgia and fasciculations. Chi-square test Nevertheless, it is associated with muscular was used to compare qualitative variables injury as it depolarizes the muscles prior to between the groups (Abbas et al., 2009). p paralysis (Fukani and Ganzberg, 2004). This value < 0.05 was considered as significant. muscular injury is manifested in the form of fasciculations and postoperative myalgia. RESULTS These muscular unwanted effects of succinylcholine have limited its usefulness and There was no significant difference in present distressing consequences for the patient characteristics in the two groups and patients after minor surgeries (Spence et al., they were well matched for age, weight and 2002). sex. Each group had 30 patients (Group A: 17 males and 13 females and Group B: 16 males In our study, the frequency of and 14 females). The mean age of Group A fasciculations was 100 percent and 23 percent patients was 39.97 ± 1.833 years (range 18-65 in the group A and B respectively. In group A, years) and of Group B was 36.63+ 1.791 the intensity of fasciculations ranged from (range 18- 65 years). moderate to severe and scored 78 on a four point scoring scale (Yun et al., 2010). The All patients in group "A" had moderate to same intensity of fasciculations with severe (100%) fasciculations, compared to succinylcholine were observed in a group of group B where only mild fasciculations were 30 patients which received two milliliters of observed in 7 patients. On a four point scoring normal saline as pretreatment prior to scale fasciculations in group A were 78 and in succinylcholine (Abbas et al., 2009). These group B it was 7. In group "A' five patients fasciculations are thought to be related to suffered from mild, 22 from moderate and agonistic action of succinylcholine on three from severe pain. In group B, 18 patients prejunctional nicotinic receptors that results in developed mild pain, at 24 hours after surgery. rapid firing (Hartman et al., 1986). The On a four point scoring scale myalgia in group incidence of succinylcholine-induced A were 58 and in group B it was 22. The fasciculations in the general population varies statistical analysis showed the frequency of between 78% and 95% (Schrieber et al., fasciculations with rocuronium pretreatment 2005). This wide range in the frequency may (23.2%) to be significantly less than with no be associated with the different induction pretreatment (100%, p< 0.001) . We observed agents used before succinylcholine or perhaps a statistically significant reduction in due to inter-observer variations (Sen et al., frequency as well as intensity of fasciculations 2003). However in group C where among group A and group C. The statistical pretreatment with rocuronium was carried out, analysis showed the frequency of only mild fasciculations were observed and the postoperative myalgias with rocuronium score was 7. The significantly lower incidence pretreatment (63.3%) to be significantly less of fasciculations in this group was pertaining than with no pretreatment (100%, p<0.001) at to the fact that nondepolarizing muscle 24 hours after surgery. We observed a relaxant-rocuronium effectively prevented statistically significant reduction in frequency fasciculations, presumably by blocking as well as intensity of myalgia among group A presynaptic nicotinic receptors. Erkola showed and group B. that the ability of d-tubocurarine to induce a strong train of four fade, an indicator of DISCUSSION prejunctional effects is correlated with its ability to prevent fasciculations (Erkola, Succinylcholine is a popular drug due to 1988). In our study statistical analysis showed the fact that it rapidly provides the ideal that fasciculations in Group B were conditions for short procedures requiring significantly less when compared to Group A endotracheal intubation (Abbas et al., 2009). (23.3% vs 100%), depicting rocuronium to be Farhat et al. 37 a potent defasciculant. The same benefit has pretreatment with nondepolarizing been mentioned by Motamed et al in their neuromuscular blocking agents slows the onset study who concluded that the incidence and time whereas decreases the duration of severity of succinylcholine-induced succinylcholine blockade (Mikat-Stevens et fasciculations can be reduced by giving al., 2000). The dose of succinylcholine was rocuronium in a dose of 0.05 mg/kg 1.5 to increased to 1.5 mg/kg because of the possible three minutes before succinylcholine antagonism between depolarizing and (Motamed et al., 1997). A study done in 2002 nondepolarizing drugs (Szalados et al., 1990) also proved the efficacy of a nondepolarizing and we found that pretreatment had no effect neuromuscular blocking agent, cisatracurium on intubation conditions. It has also been in preventing succinylcholine-induced mentioned earlier that pretreatment had no fasciculations (Mencke et al., 2002). effect on the intubating conditions (Findlay Pretreatment with rocuronium and d- and Spittal, 1996; Abbas et al., 2009). tubocurarine was found effective for prevention of succinylcholine-induced There has been a great deal of argument fasciculations (Steinberg, 2008). Both about the interval between the administration rocuronium and d-tubocurarine were found of the nondepolarizing muscle relaxant superior to cisatracurium in preventing pretreatment and the administration of succinylcholine-induced fasciculations (Joshi succinylcholine for the intubation of trachea. et al., 1999). Intervals of two, three and four minutes or even greater have been recommended (Horrow The reason for assessing the efficacy of and Lambert, 1984). However, the data rocuronium in the prevention of fasciculations suggest that a three to five minute time interval caused by succinylcholine was because of the can be safely applied for precurarization with quicker onset of action of rocuronium, due to nondepolarizing muscle relaxant to prevent which it provides effective precurarization succinylcholine-induced fasciculations and within a very short time interval (Motamed et myalgia (Pinchak et al., 1994). These intervals al., 1997). Rocuronium was used in a dose of are applied in view of the fact that shorter 0.1 mg/kg for this purpose. Smaller doses have intervals do not inhibit fasciculations and been used by other researchers. Martin et al longer intervals do not afford any additional performed a study in 1998 using rocuronium advantages (Motamed et al., 1997). In our 0.06 mg/kg 3 min before induction for study, we gave the precurarization dose of prevention of fasciculations and postoperative rocuronium, five minutes before the myalgias. They found rocuronium to be the administration of succinylcholine. This is best among all that were compared in supported by Tsui et al, who evaluated a rapid preventing succinylcholine-induced and time saving precurarization technique by fasciculations (Martin et al., 1998). Motamed using the rocuronium close to induction (Tsui et al used rocuronium in the dose of 0.05 et al., 1998). mg/kg 1.5 or 3 min before succinylcholine in their study (Motamed et al., 1997). The In our study the frequency of myalgia in administration of this pretreatment agent has group A was 100 percent ranging from mild to been recommended both on a weight related severe. On a four point scoring scale the (Abbas et al., 2009) and fixed dose regimen myalgia in this group scored 58. This high basis (Donati, 2003). We selected the weight frequency and intensity of myalgia with related dose of this nondepolarizing succinylcholine has also been observed in neuromuscular blocking agent for ease of some other studies too (Findlay and Spittal, routine administration. One of the main 1996). The incidence of myalgia with concerns related to this technique on the succinylcholine varies from 20 percent to 80 intubating conditions is that a larger dose of percent (Abrahim et al., 2008). The most succinylcholine has to be given, as frequently quoted figure is 50 percent. This is 38 Comparative study of succinylcholine and precurarization often listed as minor side effect of the drug but of postoperative myalgia. In that investigation, it may be one of the most distressing rocuronium, 0.03 mg/kg was compared with d- consequences of minor surgery for the tubocurarine, 0.05 mg/kg, as a pretreatment patients. It occurs more commonly in females two minutes before succinylcholine and resembles the aches experienced after administration. Rocuronium’s faster onset than unaccustomed exercise. The duration of this d-tubocurarine may have contributed to the discomfort is highly variable. It generally lasts findings of significantly less postoperative for two to three days but occasionally persists myalgia (Thompson-Bell et al., 1996). In for even a week (Ali, 1989). This is certainly a another study, Findlay and Spittal found that reflection of various factors which influence rocuronium because of its rapid onset of the occurrence of pain (Findlay and Spittal, action, was very efficient in reducing the 1996). Amongst a variety of reasons proposed, postoperative myalgia when a short interval postoperative myalgia has be related to was allowed before admininistering irreversible changes on muscle spindles or succinylcholine for endotracheal intubation. unsynchronized contractions of muscle fibers They found that rocuronium pretreatment resulting in shearing of connective tissues, decreased the frequency of myalgias to 20% electrolyte imbalance and release of on first post operative day and to 28.6% by prostaglandins (Hun cho et al., 1999). To day 4 (Findlay and Spittal, 1996). In another assess the specific contribution of study, the frequency of postsuccinylcholine succinylcholine on postoperative myalgia in myalgia in patients induced by propofol and patients, we standardized the perioperative succinylcholine and pretreated with 0.025 management, and the type of surgery was mg/kg atracurium was studied. The results uniform. Thus anaesthesia and surgery related showed that the frequency of myalgia were 24 factors contributing to postoperative myalgia percent without pretreatment and 1 percent in were controlled. the patients who were pretreated with atracurium. It was thus concluded that Although pretreatment with non- atracurium reduces the incidence of myalgia. depolarizing muscle relaxants seems to be This study very considerably established the effective in decreasing muscle fasciculation, efficacy of non-depolarizing agents in this its effectiveness in reducing postoperative regard (Khan and Kamal, 1997). In a further myalgia is controversial. Various attempts study, Martin et al in 1998 compared the have been made to prevent the muscle pain efficacy of d-tubocurarine, atracurium, caused after the administration of mivacurium and rocuronium. They concluded succinylcholine. One of the most useful is the that rocuronium in a dose of 0.06 mg/kg given administration of a small dose of three minutes before induction was the most nondepolarising neuromuscular blocking drug effective agent to prevent fasciculations and before administration of succinylcholine. postoperative myalgia caused by However different studies came up with succinylcholine (Martin et al., 1998). However different outcomes. Generally this some of the studies could not establish the pretreatment is reported to reduce the efficacy of pretreatment in decreasing the incidence of postoperative myalgia caused by postoperative myalgia, as was observed in a the administration of succinylcholine by 30 study by Harvey et al in 1998, concluding percent (Pace, 1990). A meta analysis rocuronium to be no better than normal saline concluded that pretreatment with in decreasing the incidence of postoperative nondepolarizing muscle relaxant, myalgia (Harvey et al., 1998). Raman and San benzodiazepine or local anaesthetic decreased found out an overall incidence of myalgia with their incidence by about 30 percent (Schreiber lidocaine pretreatment to be 22 percent and et al., 2005). Thompson-Bell in 1996 found with atracurium to be 30 percent (Raman and 0.03 mg/kg pretreatment dose of rocuronium Sen, 1997). Mencke in their study found effective in decreasing incidence and severity rocuronium failing in decreasing the incidence Farhat et al. 39 or severity of postoperative myalgia. This documented evidence of the benefit of this study was designed to compare myalgia after technique. The implication of precurarization succinylcholine with and without pretreatment will decrease the side effects of (Mencke et al., 2002). Spence concluded that succinylcholine effectively. The technique is lidocaine was significantly better than cost effective as it cuts the cost of intubation rocuronium at decreasing the severity of on each patient to one fourth as compared to postoperative myalgia at 48 hours indicating the newer nondepolarizing agents alone and that lidocaine provided better attenuation of reduced postoperative analgesic requirements postoperative myalgia (Spence, 2002). resulting in decrease in burden on the hospitals. Our results were in the support of most of the studies which were proving the efficacy of REFERENCES pretreatment with nondepolarizing agents in preventing postoperative myalgia. In group B, Abbas, N., Tariq, S., Waheed, A., Murtaza, G., 63.3 percent patients had myalgia, the severity Naqvi, N. and Khanzada, A. (2009). 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"COMPARATIVE STUDY OF SUCCINYLCHOLINE AND"