The choice of optimal modern muscle relaxants (rocuronium bromide, atracurium besilate and cisatracurius besilate) in one-day surgery in children

The study was conducted in surgical clinics of the Azerbaijan Medical University. The study included 156 children who were operated on routinely from 0 to 16 years old (risk of anesthesia I-II ASA), who used combined endotracheal anesthesia during surgery [8]. Based on the requirements of the GCP international program (Good Clinical Practice), the inclusion of children in the study was carried out only after the written consent of the parents. The studied patients were divided into 3 groups depending on the muscle relaxant used: IA (n = 52) rocuronium bromide (esmeron), IB (n = 52) atracurium besilate (tracrium), IC (n = 52) cisatracurius besilate (nimbex ). Depending on the type of general anesthesia, these groups were also divided into 2 subgroups: anesthesia based on isoflurane + fentanyl ′′ + iso ′′ and anesthesia based on sevoflurane + fentanyl ′′ + sev ′′. The main groups were also divided into 2 age subgroups: children under 2 years of age – IA1, IB1, IC1 and children from 2 to 16 years old – IA2, IB2, IC2 [9-13].

To monitor neuromuscular conduction using the TOFstimulation method, the TOF-watch device was used (Organon Teknika company, producer country, 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 of the hand. The state of neuromuscular conduction was evaluated by measuring the electromyographic responses m. adductor pollicis in response to 4 rectangular pulses (each pulse duration -0.2 ms, interval -10 sec, frequency of each pulse -2 Hz) through stimulation electrodes placed on the wrist -proximal (white) and distal (black) (3). We measured the response to the first of 4 stimuli (T 1 initial) before the introduction of muscle relaxants, the change in the value of T 1 with respect to the initial level in percent (T 1 / T1initial) and the ratio of the value of the latter to the first response in percent (T 4 / T 1 or TOF). At an amplitude of 25% of the initial value, the response to the 4th pulse (T 4 ) in TOF disappears. Responses to the 3rd and 2nd impulses (T3 and T2) cease to be recorded at values of T 1 = 20% and T 1 = 10% of the amplitude, respectively.
Clinical recovery criteria were evaluated based on: 1) Extubation time -x 1 .
3) The patient's readiness for withdrawal from the operating unit -x 3 .
4) The time from the beginning of extubation until the patient is ready to withdraw from the operating unit -x 4 = x 3 -x 1 . It should be noted that intubation and extubation of the trachea was carried out in the presence of appropriate conditions based on clinical symptoms.

Anesthesia Technique with Modern Muscle Relaxants
All children included in groups IA, IB, and IC underwent general combined analgesia using inhaled and non-inhaled anesthetics, narcotic analgesics, muscle relaxants, and mechanical ventilation.
For the purpose of sedation to all patients in 30 minutes. Before the start of anesthesia, midazolam was administered orally at the rate of 0.4 mg / kg, and atropine 0.01 mg / kg intravenously as needed.
In children under 3 years of age, the induction of anesthesia was performed with an inhaled anesthetic sevoflurane, and over 3 years old with a non-inhalational anesthetic propofol at a dose of 3.0-3.5 mg / kg. After reaching the state of anesthesia, an intravenous bolus of 0.005% fentanyl was administered at a dose of 3 μg / kg, then after 2-3 minutes, one of the studied muscle relaxants in the main doses. The tracheal intubation process was carried out when a sufficient level of myoplegia was achieved (90% T 1 suppression ventilation on a half-closed circuit with a gas flow from 3.0 to 6.0 l / min depending on age. In the subgroups ″ + iso ″ and ″ + sev ″, one of the inhaled anesthetics 1.0 MAC isoflurane and 1.3 MAC sevoflurane, respectively, was included in the gas mixture. Anesthesia was maintained by fractional administration of 0.005% fentanyl (dose equal to 3-5 μg / kg / h). During the operation, a constant level of myoplegia was achieved due to bolus intravenous injections of a maintenance dose of one of the studied muscle relaxants at T 1 up to ≥10%. After surgery, in al l patients in three groups, tracheal extubation was performed during restoration of spontaneous respiration, consciousness, and neuromuscular conduction monitor data (T 1 ≥ 75% recovery, TOF ≥ 70%).
Intraoperative infusion therapy was carried out with crystalloid solutions in volumes corresponding to the age and nature of surgical interventions. As a result of titration of the doses of muscle relaxants studied by us, primary and maintenance doses of muscle relaxants were determined depending on the type of anesthesia (Table 2). Anesthesia with the use of the drug "Sevoflurane" (subgroup ′ ′ + sev ′ ′) In the ″ + sev ″ subgroups, induction anesthesia was carried out only by inhalation in a half-closed circuit with a gas flow of 2-6 l / min, depending on the age of the child. In all cases, stepwise induction was used, starting from 0.6% to a maximum of 8 vol%.   The greatest depth of the neuromuscular block was also more pronounced in children under 2 years of age than in children of the older age group: in the IA 1 subgroup 1.5 ± 0.3% and in the IA 2 -2.5 ± 1.2%, in IB 1 -0, 8 ± 0.7% and IB 2 -1.7 ± 0.9%, IC 1 subgroup -0.7 ± 0.1% and IC 2 -1.8 ± 0.8%, respectively.
Thus, cisatracuria besilate provided the greatest depth of neuromuscular blockade, then atracurium besilate and rocuronium bromide. Therefore, in operations where surgeons require greater muscle relaxation, for example, during laparoscopic interventions, cesatracuria besilate should be preferred from the muscle relaxants studied, since it has a higher blocking effect.

Determination of the duration of a deep neuromuscular block after using the initial dosage of muscle relaxants (recovery period T 1 to 10%)
As a result of the analysis of the obtained data, certain differences were revealed depending on age when recording the duration of a deep neuromuscular block (time up to 10% recovery of T 1 ).
Thus, in children under 2 years of age in all subgroups (IA 1 , IB 1 IC 1 ) this indicator was higher; however, a statistically significant

Volume 4 -Issue 4
Copyrights @ Nasibova EM, et al. Arc Org Inorg Chem Scis 557 was administered, the time of T 1 recovery to the levels of 25%, 75%, 95% and TOF to 70% and more was estimated. According to the neuromuscular monitoring used by us, the restoration of T 1 to the level of 25% took place in all children in all the studied groups.
Recovery of T 1 to the level of 75% and TOF ≥70% in the younger age group occurred only in 21 children (83.1%) in subgroups IA 1 and IB 1 , and in 19 children (75.4%) in subgroup IC1 ( Figure 5) In the older age group, T 1 recovery to the level of 75% and TOF     Table 3.

559
Analyzing the data of the first 2 minutes from the moment of administration, we can see that the average T 1 suppression rate in children under two years of age turned out to be comparable in all the studied muscle relaxant groups. However, some advantage of rocuronium bromide has been identified. By the end of the 1st minute from the moment of administration of rocuronium bromide at a dose of 0.3 mg / kg, according to TOF-Watch, the average T 1 in the IA 1 subgroup was 58.2 ± 0.6%, with average TOF -59.3 ± 1.1%.
The degree of suppression of T 1 in other younger age subgroups at this point in time was slightly different: in the subgroup IB 1 -64.8 ± 0.6%, with average TOF -67.3 ± 0.5%, in the subgroup IC 1 -67.3 ± 0.6%, with an average TOF of -74.1 ± 0.5%. Further, the development of neuromuscular blockade progressively increased, and by the end of the 2nd and beginning of the 3rd minute from the moment of the introduction of relaxants, T 1 suppression of 90% took place in all children of the younger age group. At the same time, rocuronium bromide was superior to others in the rate of achieving maximum blockade of neuromuscular conduction. So, the average values of T 1 in the subgroup IA 1 were 8.6 ± 0.6%, with average TOF values of 17.1 ± 1.1%. In the subgroups IB 1 and IC 1 , the same indicators were: 12.3 ± 0.6% with average TOF -25.4 ± 1.1% and 12.6 ± 0.5% with TOF -27.8 ± 0.9 %, respectively ( Figure 7&8).  comparable and amounted to, on average, 9.7 ± 2.5% in the range from 97% to 99%.
As can be seen from the data presented in older age subgroups, the rate of development of maximum neuromuscular blockade was lower than in children under 2 years of age, and to achieve T 1 suppression of 95-100% it took more time. subgroups -3.0 ± 1.3 min. and cisatracuria besilate (IC 2 ) -3.5 ± 0.8 min. Moreover, an analysis of the results of the study showed that in all older age subgroups, the minimum time to reach the complete neuromuscular block, according to TOF-Watch, was observed in children aged 2 to 5 years (range from 1.8 minutes to 4.6 minutes).
And the maximum is for children over 8 years old (range from 2.3 minutes to 5.3 minutes).
The maximum suppression of T 1 in all older age subgroups was also comparable and amounted to an average of 96 ± 2.7%, with a range from 95 to 100%.
The recovery period of neuromuscular conduction in the group with ″ + sev ″. The data presented indicate that in children under 2 years of age, spontaneous restoration of neuromuscular conduction after the use of atracuria, cisatracuria besilate and rocuronium bromide is subject to a certain effect of sevoflurane, and to a different extent. In particular, the recovery index (T 1 25-75%) after the administration of the last maintenance dose in atarkuria and cisatracuria besilate increased by 33.5% and 33.6%, respectively, and in rocuronium only by 23.7% when compared with the subgroups ″ + iso ″, this confirms that inhaled anesthetics to a greater extent prolong the effects of benzylisoquinoline muscle relaxants (atracuria and cisatracuria besilate). The total time of complete recovery (T 1 0% -95%) in the atracuria besilate subgroup (IB 1 ) was the shortest and averaged 55.4 ± 1.8 minutes. The same time was longer in the subgroups of cisatracuria and rocuronium bromide and amounted to 62.5 ± 1.2 minutes and 61.8 ± 1.6 minutes, respectively.
However, statistical analysis did not reveal significant differences between relaxants -p> 0.05 ( Figure 9).

Volume 4 -Issue 4
Copyrights @ Nasibova EM, et al. Arc Org Inorg Chem Scis 561 Figure 9: Dynamics of spontaneous recovery of neuromuscular conduction in children under 2 years of age with ″ + sev ″.
The result of the study showed an increase in the recovery index in this subgroup by 23.8% relative to the performance of the subgroup ″ + iso ″. In addition, in the atracuria subgroup (IB 2 ), the average duration of complete spontaneous recovery was 52.6 ± 1.8 min versus 58.9 ± 1.8 min in the cisatracuria subgroup (IC 2 ), which was statistically significant (p <0.05). The recovery index in these subgroups relative to the subgroup ″ + iso ″ also increased by 22.5% in atracurium besilat and by 28.7% in cisatracurium besilat ( Figure 10).