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									Pakistan Journal of Pharmacology
Vol.28, No.1, January 2011, pp.33-41

                    KULSOOM FARHAT, AKBAR WAHEED,
                           Department of Pharmacology & Therapeutics,
                           Army Medical College, Rawalpindi, Pakistan
                            *Combined Military Hospital, Rawalpindi
  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:
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
     Our results were in the support of most of
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