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Aim: Comparative study of the action of the average action of muscle
relaxants atrakurium besilata (tracrium), cisatracuria besilata and rocuronium
bromide (esmerone) in small surgical interventions in children.
Material and methods: The clinical trial included 156 patients
aged from 0 to 16 years. All surgical interventions and manipulations were
performed under balanced general anesthesia with the use of moderate-effect
muscle relaxants: besilatum atracurium (tracrium), besilate cisatracuria and
bromide rocuronium (esmerone). All patients studied (n=156) were divided into 3
main groups depending on the muscle relaxant used to create and maintain
myoplegia during anesthesia: Ia group (n=52) as a muscle relaxant used
rocuronium bromide, Ib group (n=52) atracurium besilate (tracrium) was used as
a muscle relaxant, IC group (n=52) cisatracuria besilate. To conduct a
comparative assessment of the efficacy and safety of rocuronium bromide,
atracuria and cisatracuria besilat, neuromuscular conduction was monitored by
the TOF method - stimulation (“traine of four”) and performed using the
TOF-Watch instrument (Organon Ireland).
Results: We have carried out a comparative assessment of the neuromuscular
block with titrated doses of rocuronium bromide, atracuria of besylate and
cisatracuria of besylate when combined with 1.3 MAC of isoflurane (subgroup
“+iso”) tracheal intubation, maintenance of general anesthesia and spontaneous
restoration of neuromuscular conduction. The development of neuromuscular
blockade with 90% suppression of T1 in children of the older age group with the
highest rate occurred in the group with rocuronium bromide (Ia2), so the
average values by the second minute were 22.5 ± 12.9% (0-14.0-37, 0), TOF -
46.4 ± 19.7% (0-31.0-57.0), by the beginning of the 3rd minute from
the moment of introduction they were - 6.6 ± 1.8% (0-4, 0-12.0) with average
values of TOF - 28.2 ± 14.8 (0-5, 0-100).
Conclusion: 1) When using isoflurane, lower loading doses of besylate atracuria to
0.4 mg/kg, cisatracuria of besylate to 0.12 mg/kg and rocuronium bromide to
0.45 mg/kg ensure sufficient neuromuscular block depth (T1 suppression from 90%
and higher). 2) The time of onset of action in children under 1 year old does
not significantly change when using isoflurane. And in older children,
significant differences were obtained only when comparing rocuronium bromide at
doses of 0.45 mg/kg and 0.6 mg/kg (p<0.05).
Keywords: Atracurium besylate, Cisatracuria besylate, Rocuronium bromide
INTRODUCTION
The choice of optimal muscle relaxants for small surgical interventions
in children is one of the urgent problems of pediatric anesthesiology.
AIM OF THE STUDY
Comparative study of the action of the average action of muscle relaxants
atrakurium besilata (tracrium), cisatracuria besilata and rocuronium bromide
(esmerone) in small surgical interventions in children.
MATERIAL AND
METHODS OF THE STUDY
The research was conducted in AMU surgical clinics from 2000 to 2018. The
study included 156 children aged 0 to 16 years operated on in conditions of
one-day surgery. During the study, all children were divided into 3 main groups
depending on the muscle relaxant used:
Ia (n=52) - with the use of rocuronium bromide (esmerone), Ib (n=52) -
with the use of atracuria, besylate (tracrium), Ic
Depending on the type of general
anesthesia, these groups were divided into 2 subgroups: anesthesia based on
isoflurane+fentanyl “+iso”, anesthesia based on sevoflurane+fentanyl “+sev”.
Also, the main groups were divided into 2 age subgroups: children under 1 year
of age – Ia1, Ib1, Ic1 and children from 2 to 16 years old – Ia2, Ib2, Ic2. To
conduct a comparative assessment of the efficacy and safety of rocuronium
bromide, atracuria, and cisatracuria of besilate, dynamic monitoring of the
neuromuscular conduction indices was performed by the acceleorometric method.
TOF - stimulation (“traine of four”) monitoring of neuromuscular conduction was
carried out using the TOF-Watch (Organon Ireland) device. All children in
groups Ia, Ib and Ic were given general combined anesthesia with the use of
inhalation and non-inhalation anesthetics, narcotic analgesics, muscle
relaxants. After the onset of narcotic sleep, 0.005% fentanyl at the rate of 3
μg/kg was injected intravenously with a bolus and then in 2-3 min one of the
studied muscle relaxants in basic doses. Tracheal intubation was performed when
a sufficient level of myoplegia was reached (90% of T1 suppression
according to TOF-Watch) with the corresponding endotracheal tubes. Maintenance
of anesthesia in all patients was carried out in conditions of mechanical
ventilation on a semi-closed circuit with a gas flow from 3.0 to 6.0 l/min,
depending on age. In the “+iso” and “+sev” subgroups, one of the inhalation
anesthetics 1.0 MAK isoflurane and 1.3 MAK sevoflurane, respectively, was
included in the gas-narcotic mixture. The constant level of myoplegia during
the operation was provided only by bolus intravenous doses of maintenance doses
of one of the studied muscle relaxants when T1 is restored to ≥ 10%.
At the end of surgery, all the studied patients in groups Ia, Ib and Ic, under
adequate conditions determined by clinical signs and data from the
neuromuscular conduction monitor (T1 recovery ≥ 75%, TOF ≥ 70%),
trachea extubation was performed. Considering the strong irritating effect of
isoflurane on the upper respiratory tract, induction anesthesia in the “+iso”
subgroup was performed by intravenous administration of prpofol at the rate of
4.0-4.5 mg/kg. After reaching the superficial level of the surgical stage of
anesthesia, they switched to maintaining anesthesia with isoflurane, with an
exposure time of 10 min. At the stage of tracheal intubation, after intravenous
administration of 0.005% fentanyl 3 mg/kg, either rocuronium bromide was
administered at a dose of 0.45 mg/kg or atracurium besilate - 0.4 mg/kg or
cisatracurium besilate - 0.12 mg/kg. Maintenance of anesthesia in all patients
from the “+iso” subgroup was performed with 1 MAK isoflurane. Supporting doses
of muscle relaxants in children of this group were 0.1 mg/kg for rocuronium
bromide, 0.15 mg/kg for besilat atracuria and 0.02 mg/kg for besilate
cisatracuria. Isoflurane delivery was stopped when skin sutures were applied
[1-4].
In the subgroups “+sev”,
induction anesthesia was carried out only by an inhalation method with a
semi-closed circuit with a gas flow of 2-6 l/min, depending on the age of the
child. In all cases, step-by-step induction was used, ranging from 0.6% to a
maximum of 8 vol%. Exposure ranged from 2-5 min, after completely falling
asleep, the concentration of sevoflurane in the inhaled mixture gradually decreased
to the required level of 1.3 IAC on expiration. After intravenous
administration of 0.005% fentanyl at a dose of 2 µg/kg, rocuronium bromide was
administered at a dose of 0.3 mg/kg or atracurium besilate - 0.3 mg/kg or
cisatracurium besilate - 0.1 mg/kg. Upon reaching 90% T1
suppression, tracheal intubation was performed. The maintenance of anesthesia
in all patients of this subgroup was carried out by 1.3 MAC sevoflurane.
Supporting doses of muscle relaxants in children of this group were: rocuronium
bromide - 0.1 mg/kg of atracuria, besylate - 0.15 mg/kg, cisatracuria, of
besylate - 0.02 mg/kg. The supply of sevoflurane, as in anesthesia with
isoflurane, was stopped at the end of the operation [5-8].
To conduct a comparative
assessment of the efficacy and safety of rocuronium bromide, atracuria and
cisatracuria of besilate, dynamic monitoring of the neuromuscular conduction
indices was performed by the acceleorometric method. TOF-stimulation (“traine
of four”) was monitored using a TOF-Watch instrument (Organon Ireland). The
device is equipped with a piezoelectric transducer (accelerometer sensor),
which is fixed on the inner surface of the distal phalanx of the thumb. The
state of neuromuscular conduction was assessed by measuring electromyographic
responses of m. adductor pollicis in response to 4 consecutive supramaximal
irritation of the ulnar nerve with a rectangular-shaped impulse with a duration
of 0.2 ms, 2 Hz every 10 s through stimulating electrodes placed on the wrist -
proximal (white) and distal (black) [9,10].
The response to the first of
four stimulations (Tinx) before the introduction of muscle relaxants
was measured, the change in the T1 value relative to the initial
value in percent (T1/T1inx) and the ratio of the latter
value to the first answer in percentage (T4/T1 or TOF).
With amplitude of 25% of the original value, the response to the 4th
pulse (T4) in the TOF disappears. Answers to the third and second
pulses (T3 and T2) cease to be recorded at T1=20%
and T1=10% amplitude, respectively. A clinically stable level of
relaxation corresponds to at least a 90% decrease in amplitude compared with
the initial level (T1 ≤ 10%). At the same time, only one response to
stimulation in the TOF mode is detected and satisfactory conditions are
provided for carrying out surgery. The depth of the block was calculated as the
difference T1inx taken as 100% and the value (T1/T1inx)
at a given time [11].
RESULTS AND DISCUSSION OF THE STUDY
Isoflurane is one of the most
widely used inhaled anesthetics at the stage of maintaining general anesthesia
in children. The ability of isoflurane to exert a rather pronounced and
reversible muscle relaxant effect was used by us to develop a technique of
general anesthesia using lower doses of muscle relaxants. We carried out a
comparative assessment of the neuromuscular block with titrated doses of
rocuronium bromide, atracuria besilata and cisatracuria besilate when combined
with 1.3 IAC isoflurane (“+iso” subgroup) at the stages of tracheal intubation,
maintaining general anesthesia and spontaneous recovery of neuromuscular
conduction.
Induction into general
anesthesia in children of this group was carried out by intravenous
administration of propofol before reaching the surgical stage. After switching
to 1.3 IAC isoflurane anesthesia scheme and subsequent intravenous
administration of 0.005% fentanyl at a dose of 3 µg/kg and loading doses of
rocuronium bromide 0.45 mg/kg (1.5x ED95) or cisatryurium besylate - 0.12 mg/kg
(2.5x ED95). Analyzing the research data, we can say that in young children the
maximum rate of development of neuromuscular blockade differed in the
rocuronium bromide group at a dose of 0.45 mg/kg. Already after the first
minute from the moment of introduction, the average values of T1
were 59.5 ± 24.6% (4.0-47.0-73.0) from the initial level, with average values
of TOF - 66.7 ± 22.4% (0-85.5-105.0). In the subgroup with cisatracurie (Ic),
at the dose of 0.12 mg/kg, the lowest rate of neuromuscular conduction
depression was observed, where after 1 min from the moment of administration T1
was still quite high and averaged 68.1 ± 20.6% (7.0-73.0-95.0) from the initial
level, with average values of TOF - 75.0 ± 24.5% (0-89.2-104.5). The
administration of a loading dose of 0.4 mg/kg of besilac atracuria in the Ib
subgroup provided T1 suppression in most patients by the end of the first
minute - 62.5 ± 22.8% (6.0-69.0-89.0) of the initial level, with average values
of TOF - 71.5 ± 20.9% (0-87.5-103.0), which is less than that of rocuronium
bromide, but more than that of cisatracuria of besylate. In children older than
1 year, the developmental dynamics of the neuro-muscular blockade during the
first 2 min from the moment of administration had a similar picture with the
younger age group, but was more extended in time. The variability of the
duration of the initial doses of atracuria, cisatracuria of besylate and
rocuronium bromide was observed in patients in the older age group. So, in
children from 1 to 5 years, the duration of deep NMB is slightly longer than in
children older than 5 years: in subgroup Ib2 - 36.4 ± 8.2 min and 32.2 ± 7.6
min, in the subgroup Ic2 - 39.0 ± 6.9 min and 35.6 ± 8.4 min and in subgroup
Ia2 - 21.4 ± 9.8 min and 19.8 ± 10.8 min, respectively. In our work, we also
studied the method of endotracheal general anesthesia based on sevoflurane with
the use of low doses of rocuronium bromide, atracuria and cisatracuria of
besylate during various surgical interventions. Introductory anesthesia in all
children of this group was performed with sevoflurane (+sev) until reaching the
surgical stage. After reaching the concentration of sevoflurane on expiration
of 1.3 MAC (according to the gas analyzer) and the subsequent administration of
fentanyl at a dose of 3 μg/kg, loading doses of atracuria 0.3 mg/kg in group Ib
followed, cisataruria 0.1 mg/kg in group Ic and rocuronium bromide 0.3 mg/kg in
group Ia. Analyzing the data of the first 2 min from the moment of
administration, it can be seen that the average rate of suppression of T1
in children under the age of 1 year turned out to be comparable in all studied
groups of muscle relaxants [12,13]. However, some advantage of rocuronium
bromide was revealed. By the end of the 1st minute from the moment
of introduction of rocuronium bromide at a dose of 0.3 mg/kg, according to
TOF-Watch, the average values of T1 in the subgroup Ia1 were 60.1 ±
21.2% (5.0-50.0-77.0), with average TOF values of 69.5 ± 16.3% (0-79.5-99.6).
Reducing the loading dose of the studied muscle relaxants with the inclusion of
sevoflurane in the anesthesia scheme, slightly lengthened the time to achieve
satisfactory conditions for tracheal intubation and the development of maximum
NMB in children less than 1 year of age, compared with higher doses in the
group with isoflurane. The possibility of performing tracheal intubation for
1.5-2 min in children under one year old with excellent and good conditions is
still preserved. In children older than 1 year, only rocuronium bromide at a
dose of 0.3 mg/kg provided the possibility of tracheal intubation within 1.5-2
min with excellent and good conditions. In the older age group with sevoflurane
Ib2, the recovery time of T1 to 10% varied from 26.0 to 55.3 min and
averaged 33.7 ± 5.8 min (p<0.05). The duration of deep muscle relaxation in
the Ic2 subgroup after administration of the initial dose of cisatracuria at a
dose of 0.1 mg/kg was 37.6 ± 7.7 min in the range of 32.0-59.0 min (p<0.05).
Statistically significant differences when comparing between the ages
categories of children in subgroups, the studied muscle relaxants were not
identified. In the older age group Ia2, the average duration of the initial
dose of 0.3 mg/kg was 23.7 ± 7.2 min with a range from 17.5 to 43.5 min. When
comparing the results obtained in the group with sevoflurane with the “+iso”
group, higher doses of the studied muscle relaxants were used, no statistically
significant difference in time from the moment of administration to 10%
recovery of T1 was observed. This can be explained by the fact that
the potentiating effect of sevoflurane is more powerful and manifests itself
earlier than that of isoflurane, due to the lower blood/gas solubility
coefficient (0.65 and 1.43, respectively), which ensures a quick equalization
of its concentration in the alveolar air, in the blood and muscles, it was also
found that the potentiating effect of sevoflurane in children is more
pronounced in subgroups using benzylisoquinoline muscle relaxants atracuria and
cisatracuria besylate compared with rocuronium bromide [14,15].
CONCLUSION
1. When
using isoflurane, lower loading doses of besylate atracuria to 0.4 mg/kg,
cisatracuria of besylate to 0.12 mg/kg and rocuronium bromide to 0.45 mg/kg
allow for sufficient neuromuscular block depth (T1 suppression from
90% and above).
2. Reduction
of basic doses of besilat atracuria to 0.1 mg/kg, rocuronium bromide up to 0.3
mg/kg under anesthesia with the inclusion of 1.3 IAC sevoflurane provides a
sufficient level of relaxation in children under 1 year old during operations
performed traditionally or laparoscopically. And these doses of the studied
muscle relaxants do not provide a sufficient level of muscle relaxation during
laparoscopic operations in children over the age of 1 year, which is manifested
in the deterioration of comfort and working conditions of surgeons.
3. The
degree of influence of sevoflurane on the duration of the action of the main
and supporting doses of atracuria and cisatracuria of besylate is higher than
that of rocuronium bromide.
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