PATRICIA A. KAPUR
Comparison of Rocuronium and Mivacurium to
Succinylcholine During Outpatient Laparoscopic Surgery
Jun Tang, MD, Girish P. Joshi, MB BS, MD, FFARCSI, and Paul F. White, rhD, MD, FANZCA
Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, Dallas, Texas
Tracheal intubating conditions and neuromuscular ef- significantly shorter than for rocuronium (158+ 76s)or
fects of succinylcholine, rocuronium, and mivacurium mivacurium (210t- 93 s).Moreover, the onset timesfor
were studied in 100healthy women undergoing out- rocuronium were significantly shorter than mivacu-
patient laparoscopic surgery. After a standardized rium. The recovery times (of Tl to 25% of the control
fentanyl-thiopental induction, tracheal intubation was value) were significantly shorter with succinylcholine
facilitated with succinylcholine 1 mg/kg in Groups I and mivacurium than rocuronium. Significantly fewer
(n = 23)and II (n = 25),rocuronium 0.6mg/kg in Group patients needed reversal of residual neuromuscular
III (n = 27), or mivacurium 0.2mg/kg in Group IV (n = blockade after mivacurium compared to rocuronium.
25). If clinically indicated, bolus dosesof rocuronium One patient in Group I and six patients in Group IV
5-10 mg (Groups I and III) or mivacurium 2-4 mg displayed erythema on the upper body. Postoperative
(Groups II and IV) were administeredduring the main- myalgia were experienced by 16% of the patients in
tenance period. Anesthesia was maintained with des- Groups I and II comparedto none in Groups III and IV.
flurane and nitrous oxide 60%in oxygen. At the end of There was no difference in the incidence of postopera-
the surgery, residual neuromuscular block was re- tive nauseaand vomiting among the four groups. In
versed with edrophonium 0.5 mg/kg and atropine conclusion, rocuronium appears to be an acceptable al-
10 pg/kg, if needed.The neuromuscular function was ternative to succinylcholine for tracheal intubation.
assessed using electromyography with a train-of-four However, rocuronium’s longer duration of action in-
mode of stimulation every 10s at the wrist. Intubating creasesthe need for reversal drugs. When rapid tra-
conditions 90 s after succinylcholine and rocuronium cheal intubation is unnecessary,mivacurium is alsoan
were significantly better than after mivacurium. The acceptable alternative to succinylcholine and is associ-
onsettime (from the end of injection until 95%suppres- ated with a more rapid spontaneous recovery than
sion of the first twitch [Tl]) for succinylcholine (63 t rocuronium.
21 s and 62 + 17s in Groups I and II, respectively) were (Anesth Analg 1996;82:994-8)
oncerns regarding the side effects of succinyl- comparisons of these two nondepolarizing muscle re-
choline (1) and the neuromuscular reversal laxants with succinylcholine have been performed in
drugs (2,3) have increased interest in the use of the ambulatory setting.
more rapid and shorter-acting nondepolarizing neu- This randomized protocol was designed to evaluate
romuscular blocking drugs in the ambulatory setting. the intubating conditions at 90 s after rocuronium
The availability of rocuronium (Zemuron@) and miva- (0.6 mg/kg) or mivacurium (0.2 mg/kg) compared
curium (Mivacronm) provide anesthesiologists with al- with succinylcholine (1.0 “g/kg). The recovery char-
ternatives to succinylcholine for outpatient anesthesia. acteristic of rocuronium and mivacurium were also
Rocuronium has been reported to provide adequate compared with those of succinylcholine. Finally, peri-
intubating conditions with a rapid onset (4). Although operative side effects were reported when the two
mivacurium has a slower onset (5), it has a duration nondepolarizing drugs were used alone or in combi-
of action which facilitates spontaneous recovery of nation with succinylcholine.
neuromuscular function (2,3). To date, no direct
Presented in part at the 1995 meeting of the American Society of
Anesthesiologists, Atlanta, GA. Methods
Accepted for publication January 26, 1996. One hundred healthy, consenting, nonpregnant women
Address correspondence and reprint requests to Paul F. White, scheduled for outpatient laparoscopic surgery were
PhD, MD, FANZA, Department of Anesthesiology and Pain Man-
agement, University of Texas Southwestern Medical Center, 5161 randomly assigned to one of four muscle relaxant
Harry Hines Blvd., Dallas, TX 75235-9068. treatment groups according to a protocol approved by
01996 by the International Anesthesia Research Society
994 Anesth Analg 1996;82:994-8 0003.2999/96/$5.00
ANESTH ANALG AMBULATORY ANESTHESIA TANG ET AL. 995
1996;82:994-8 SUCCINULCHOLINE VS ROCURONIUM VS MIVICURIUM
the institutional review board. Patients with antici- (25-50 pg) were administered, if necessary, to main-
pated airway difficulties, neuromuscular disorders, tain the heart rate within 20% of the preinduction
metabolic diseases, impaired renal or hepatic function, (baseline) values. All patients were mechanically ven-
allergic reactions to any study drugs, history of tilated to maintain end-tidal carbon dioxide between
asthma, or currently taking medications known to alter 32 and 36 mm Hg. The esophageal temperature was
muscle transmission were excluded from the study. maintained between 36 and 37°C. In addition, heart
On arrival to the operating room, patients were rate, noninvasive arterial blood pressure, Spa,, and
administered intravenous (IV) midazolam (2 mg) and esophageal temperature were recorded at 5-min inter-
anesthesia was induced with fentanyl (1.5 Fg/kg IV) vals. Residual neuromuscular blockade was not rou-
and thiopental(4 mg/kg IV). After induction of anes- tinely antagonized at the end of the operation if the
thesia, neuromuscular transmission was assessed us- patient was awake with adequate spontaneous venti-
ing electromyography (Relaxograph; Datex, Helsinki, lation and could perform a 5-s head lift. If reversal of
Finland). Recordings of the contractions of the adduc- residual neuromuscular blockade was required, edro-
tor pollicis muscle were obtained by stimulating the phonium 0.5 mg/kg and atropine 10 pg/kg was ad-
ulnar nerve at the wrist through surface electrodes ministered at the end of the surgery.
with supramaximal square-wave train-of-four (TOF) Clinical signs of histamine release (e.g., cutaneous
stimuli of 0.2 ms duration every 10 s. The electromyo- erythema) were recorded. A blinded observer, re-
graph was calibrated using baseline stimulation for corded the incidence and severity of nausea and vom-
1 min in all patients. After calibrating the electromyo- iting using a visual analog scale preoperatively, post-
graph, patients received one of four muscle relaxant operatively every 30 min for 120 min, and 24 h after
regimens during anesthesia. Group I received succi- discharge by a follow-up phone call. An emetic epi-
nylcholine 1 mg/kg for intubation followed by rocu- sode was defined as a single vomiting or retching
ronium 5- to lo-mg boluses for maintenance, Group II event, or any combination of these events which oc-
received succinylcholine 1 mg/kg for intubation fol- curs in rapid sequence (5 1 min between events).
lowed by mivacurium 2- to 4-mg boluses for mainte- Events separated by more than 1 min were considered
nance, Group III received rocuronium 0.6 mg/kg for to be two separate events. Incidence of postoperative
intubation followed by rocuronium 5- to lo-mg bo- muscle pain (pain in the neck muscles) was assessed
luses for maintenance, and Group IV received miva- immediately prior to discharge and 24 h later by a
curium 0.2 mg/kg followed by mivacurium 2- to 4-mg follow-up phone call.
boluses for maintenance. Data are summarized as mean 2 SD in the tables.
Ninety seconds after the administration of the intu- These data were analyzed using analysis of variance
bating dose of the muscle relaxant, laryngoscopy was and 2 test as appropriate. A P value of less than 0.05
performed by an anesthesiologist who was unaware was considered statistically significant.
of the twitch response. The laryngoscopy was graded
using a three-point scale: excellent (good jaw relax-
ation and completely open vocal cords without move-
ment); good (adequate jaw relaxation but some move- Results
ment of the vocal cords); and poor (incomplete jaw The four muscle relaxant treatment groups were com-
relaxation and moving vocal cords). The trachea was parable with respect to demographic characteristics,
intubated only if the conditions were graded as excel- intraoperative anesthetic medication requirements, as
lent or good at 90 s. If necessary, repeat laryngoscopy well as surgical and anesthetic times (Table 1). The
for tracheal intubation was performed on achieving intubating conditions at 90 s after administration of
maximum blockade. In addition, the onset time (time the neuromuscular blocking drug were judged to be
from the end of injection until suppression of the first good-to-excellent in all patients in Groups I and III
twitch [Tll of the TOF to 5% of its control value) was (Table 2). However, intubation conditions were
measured. The recovery from neuromuscular block graded poor and intubation was delayed in one pa-
was allowed to occur spontaneously and the time of tient in Group II and seven patients in Group IV
recovery of Tl to 25% of the control value (so called (Table 2). The patient from Group II was graded poor
“clinical duration of action”) was also recorded. Main- because of difficulty in visualizing the vocal cords
tenance doses of rocuronium or mivacurium were despite good jaw relaxation. The onset time to achieve
administered only if clinically necessary (i.e., if the a 95% decrease in Tl was significantly shorter in
patients developed an increased peak inspiratory Groups I and II compared with Groups III and IV
pressure or if the surgeons complained of inadequate (Table 3). Compared with Group IV, the onset times
relaxation). were significantly shorter in Group III (Table 3).
After tracheal intubation, anesthesia was main- The duration to 25% recovery of Tl was signifi-
tained with desflurane (3%-4%) and nitrous oxide cantly longer in Group III compared with the other
60% in oxygen. Supplemental doses of IV fentanyl three groups (Table 3). When compared with Group
996 AMBULATORY ANESTHESIA TANG ET AL. ANESTH ANALG
SUCCINULCHOLINE VS ROCURONIUM VS MIVICURIUM 1996;82:994-8
Table 1. Demographic Data, Intraoperative Anesthetic Medication Requirements,and Clinical Data in the Four
I II III IV
Number (rz) 23 25 27 25
Age (yr) 28 t 7 29 + 8 31 + 9 30 2 7
Weight (kg) 68 ? 11 73 + 20 69 + 15 67 -c 14
Height (in.) 63 k 3 64 + 3 63 2 3 63 ? 2
Fentanyl (pg) 163 2 75 167 + 57 176 + 74 161+ 83
Thiopental (mg) 276 2 53 279 2 69 286 2 64 276 + 55
Surgical time (min) 60 ? 31 56 i- 29 64 t 27 51 + 33
Anesthetic time (min) 82 ?I 31 79 t 30 89 t 30 74 + 40
Tracheal intubating dose of muscle relaxant (mg) 71 t 13 73 2 19 42 2 10 14 + 3
Maintenance dose of musclerelaxant (mg) 17 + 12 924 13 2 5 6k6
Number of patients requiring maintenancedoses(n) 17 22 7 13
Values are mean + SD.
Table 2. Conditions on Laryngoscopy at 90 s After patients had good-to-excellent laryngoscopic condi-
Administration of the Neuromuscular Blocking Drugs tions at 90 s after succinylcholine or rocuronium com-
Group pared with mivacurium. The laryngoscopy was per-
formed at 90 s because it was an intermediate between
I II III IV the intubating times reported for rocuronium (60 s)
Number (n) 23 25 27 25 and mivacurium (120 s). Optimal intubating condi-
Excellent (n) 22 20 24 13% tions after rocuronium (0.6 mg/kg) were similar to
Good (n) 1 4 3 5 those reported previously (6-10). The intubating con-
Poor (n) 0 1 0 7* ditions with mivacurium (0.2 mg/kg) at 90 s were
* P < 0.05 compared with the other groups. acceptable in 72% of the patients. Of interest, Maddi-
neni et al. (ll), using the same dose, reported accept-
IV, the time to 25% recovery of Tl was significantly able intubating conditions in only 65% of patients at
shorter in Groups I and II (Table 3). Due to the shorter 120 s. It is likely that the intubating conditions in the
duration of muscle relaxant activity in Groups I, II, mivacurium group would have been improved by
and IV, a greater number of these patients received using the larger dose of mivacurium (0.25 mg/kg)
maintenance doses (Table 1). The residual neuromus- which is currently recommended.
cular block had to be antagonized in a significantly Although the intubating conditions after rocuro-
greater number of patients in Group III compared nium (0.6 mg/kg) were similar to succinylcholine
with the other three groups (Table 3). Prior adminis- (1.0 mg/kg), its onset time at the adductor pollicis
tration of succinylcholine for tracheal intubation had muscle was significantly longer than succinylcholine.
no apparent influence on the neuromuscular effects of The comparable intubating conditions at 90 s may be
rocuronium or mivacurium during the maintenance related to a more rapid onset of paralysis in the laryn-
period. One patient in Group I and six patients in geal compared with the peripheral (adductor pollicis)
Group IV displayed erythema on the upper body. muscle groups (12,13). Previous studies have sug-
However, none of these patients required any treat- gested that the onset time at the laryngeal muscles
ment for this transient side effect related to histamine after rocuronium is similar to the onset time after
release. Of importance, 16% of the patients in Groups succinylcholine (12).
I and II experienced postoperative myalgia compared The onset time of succinylcholine in the present
with none in Groups III and IV. There was no dif- study was similar to those reported previously
ference in the incidence of nausea and vomiting (6,8,11). In previous investigations, the mean onset
among the four groups (Table 3). The visual analog times of rocuronium ranged between 58 and 172 s. The
score scores for nausea and vomiting among the differences in onset times between various studies
four groups were similar at all time points (data not may be due to the use of different modes of nerve
reported). stimulation (i.e., TOF versus single twitch) and differ-
ent anesthetic techniques. The use of the TOF mode of
stimulation was associated with shorter onset times
Discussion compared with the use of single-twitch stimulation
In this study comparing succinylcholine, rocuronium, (14). Interestingly, there was still a wide variation in
and mivacurium, a significantly larger number of the the onset times of rocuronium 0.6 mg/kg (58-130 s)
ANESTH ANALG AMBULATORY ANESTHESIA TANG ET AL. 997
1996;82:994-8 SUCCINULCHOLINE VS ROCURONIUM VS MIVICURIUM
Table 3. Onset and SpontaneousRecovery Characteristics,Side Effects, and Direct Costsin the Four Treatment Groups
Group I Group II Group III Group IV
(n = 23) (n = 25) (n = 27) (n = 25)
Time to 95% Tl depression(s) 63 2 21 62 5 17 158 t 76* 210 ‘- 93X$
Recovery to 25% Tl (min) 10 t 2 10 2 2 56 ” 17* 20 ‘I 6+$
Need for reversal (n) 6 3 21§ 4
Time from last dose of rocuronium or mivacurium 42 t 28t 19 2 6 67 +- 32s 13 +- 3
to assessment reversal (min)
Clinical signsof histamine release(n) 1 0 0 6
Myalgias (n) 4 4 0* 0%
Nausea (n) 7 5 9 9
Vomiting (n) 2 3 ” 4
Acquisition costsof muscle relaxants and reversal 19 5 10 18 ? 6 28 9s 19 t 7
drugs per patient ($)
Values are mean k SD.
*P < 0.05 compared with Groups I and II.
t P < 0.05 compared with Groups II and IV.
$P < 0.05 compared with Group III.
§P < 0.05 compared with Groups I, II, and IV.
using only the TOF-stimulation mode (6,8,9,15). Puh- vomiting (3). However, the incidence of postopera-
ringer et al. (10) and Cooper et al. (16) reported onset tive emesis has been reported to be significantly less
times of 72 and 89 s, respectively, using single-twitch in patients receiving edrophonium and atropine for
stimulation. The onset times after mivacurium ob- neuromuscular reversal compared with those receiv-
served in the current study (210 s) were similar to ing a neostigmine-glycopyrrolate combination (3). Al-
those reported by other investigators (17,18), but though a significantly larger number of patients re-
longer (97 s) than those reported by Maddineni et al. ceiving rocuronium for intubation and maintenance
(11). (Group III) required neuromuscular reversal drugs,
The clinical duration of action after rocuronium the incidence of nausea and vomiting was similar in
(0.6 mg/kg) observed in the present study was longer all four treatment groups. This finding is probably
than that reported previously (6,7,10,15). This may be related to the fact that an edrophonium-atropine com-
due to a greater potentiation of rocuronium-induced bination was used for neuromuscular reversal.
neuromuscular blockade by desflurane as compared With respect to the drug acquisition costs, the use of
to isoflurane (which was used in the previous studies). succinylcholine for tracheal intubation, followed by
Of interest, the clinical duration after mivacurium ob- either mivacurium or rocuronium for maintenance or
tained in this study was similar to previous studies use of mivacurium alone, would appear to be advan-
(7,ll). It is not surprising that the need for reversal tageous compared to rocuronium alone (Table 3).
drugs after the use of mivacurium for intubation was However, in examining the cost-effectiveness, it is
significantly decreased compared with rocuronium. important to consider not only the “direct” costs of the
Furthermore, these data and the previous reports neuromuscular blocking drugs and reversal drugs,
(6,11,19,20) suggest that in healthy patients succinyl- but also the “indirect” costs (25,26). The indirect costs
choline had no significant effect on a subsequent would include those associated with the treatment of
rocuronium- or mivacurium-induced neuromuscular the side effects related to the muscle relaxant and
block. reversal drugs (e.g., histamine release, myalgias, dry
The use of volatile anesthetics, particularly enflu- mouth, postoperative nausea and vomiting), addi-
rane (21), isoflurane (221, and desflurane (23), can tional length of stay in the operating room and recov-
potentiate the effectiveness of neuromuscular block- ery room, and unanticipated hospitalizations. In addi-
ing drugs. Propofol is reported to produce significant tion, the increased patient discomfort, anxiety, and
depression of the laryngeal reflexes (24) and, thus, stress related to the side effects are important human
may provide better intubating conditions than thio- factors that need to be considered in any cost-
pental. It is likely that the use of propofol for induction effectiveness analysis. The clinical significance of my-
of anesthesia and administration of an inhaled anes- algias associated with the use of succinylcholine and
thetic just prior to tracheal intubation would improve the increased nausea and vomiting with neuromuscu-
intubating conditions with all three muscle relaxants. lar reversal drugs remains controversial. Furthermore,
The muscarinic effects of the neuromuscular re- the “cost” impact of these side effects is unknown.
versal drugs on the gastrointestinal tract may in- Finally, it can be argued that the costs of neuromus-
crease the incidence of postoperative nausea and cular blocking drugs and their antagonists is of limited
998 AMBULATORY ANESTHESIA TANG ET AL. ANESTH ANALG
SUCCINULCHOLINE VS ROCURONIUM VS MIVICURIUM 1996;82:994-8
clinical significance, since they represent only a small 11. Maddineni VR, Mirakhur RK, McCoy El?, et al. Neuromuscular
effects and intubating conditions following mivacurium: a com-
fraction of the overall hospital costs (26).
parison with suxamethonium. Anaesthesia 1993;48:940-5.
In conclusion, if rapid tracheal intubation is re- 12. Meistelman C, Plaud B, Donati F. Rocuronium (ORG 9426)
quired, rocuronium appears to be an acceptable alter- neuromuscular blockade at the adductor muscles of the larynx
native to succinylcholine; however, its longer duration and adductor pollicis in humans. Can J Anaesth 1992;39:665-9.
of action increased the need for neuromuscular rever- 13. Wright PM, Caldwell JE, Miller RD. Onset and duration of
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sal drugs. The rapid spontaneous recovery from the
laryngeal adductor muscles in anesthetized humans. Anesthe-
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even in patients undergoing brief ambulatory proce- tion of mivacurium: comparison of two different modes of nerve
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15. Cooper RA, Mirakhur RK, Maddineni VR. Neuromuscular ef-
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