CC BY
6
III. SURGERY
МРНТИ 76.31.29
Kuandykov T.K. —
orcid.org/0000-0001-9491-6260
Mutagirov V.V. —
orcid.org/0000-0001-5561-1413
Tunushbaev A.P. -
orcid.org/0000-0002-1406-5687
Mahatov A.T. -
orcid.org/0000-0002-7848-1815
Alimanov N.A. -
orcid.org/0000-0002-5001-4764
Sherbayev S.T. -
orcid.org/0000-0003-3038-5928
Dosymbetov K.I. -
orcid.org/0000-0003-0352-6596
Musadilov K.T. -
orcid.org/0000-0003-2143-8573
Kudaibergenov E.K. -
orcid.org/0000-0001-5627-8501
Pahmanberdi B.Zh. -
orcid.org/0000-0002-8190-0910
Keywords
postoperative pain, opioid receptor antagonist-agonists, analgesia efficacy
ASSESSMENT OF THE SAFETY AND CLINICAL EFFICACY OF THE PAINKILLER RUBUFIN IN SURGICAL PATIENTS IN THE POSTOPERATIVE PERIOD
Kuandykov T.K., Mutagirov V.V., Tungushbaev A.P., Mahatov A.T., Alimanov N.A., Sherbaev S.T., Dosymbetov K.I., Musadilov K.T., Kudajbergenov E.K., Rahmanberdi B.Zh.
National Scientific Center of Surgery named after A.N. Syzganov, Almaty, Kazakhstan
Abstract
Rubufin was applied in patients of the National Scientific Center of Surgery named after A.N. Syzganov in the postoperative period. Studied 150 patients aged 22 to 65 years. The effectiveness of anesthesia was assessed by changing the following criteria: blood pressure, pulse, heart rate, oxygen saturation in peripheral blood, gas composition and acid-base state of the blood, and a visual analogue pain rating scale. The effect of rubufin on changes in blood biochemical parameters was studied. A decrease in pain syndrome was revealed by 1.5 times, a decrease in heart rate from 95.6 ± 8.8 to 83.2 ± 11.7 per minute, and respiratory rate from 22.4 ± 2.7 to 16.3 ± 2.1 in minute, a decrease in mean arterial pressure is proportional to a decrease in pain, absence of respiratory depression, an increase in oxygen tension in the blood from 109.5 ± 23.4 mm Hg. up to 112.4 ± 16.6 mm Hg, no changes in blood biochemical parameters when using rubufin. Thus, it has been proven to be highly effective in anesthetizing patients with moderate and severe pain syndrome after extensive surgical interventions, and to improve the indicators of blood oxygenation and stroke volume associated with the elimination of pain syndrome.
Хирургиялык наукастарда отадан кешнп кезецде «Рубуфин» дэршш препаратыньщ каутаздтн жэне клиникалык ттмдштн баFалау
Туйш свздер
отадан Kem^i ауырсыну, oпиoидты рвцвптoрлaрдын aгонист-aнтaгонистeрi, aнaлгвзия тшмдЫп
КуандыковТ.К.. Мутагиров В.В., Тунгушбаев А.П., Махатов А.Т., Алиманов Н.А., Шербаев С.Т., Досымбетов К.И., Мусадилов К.Т., Кудайбергенов Е.К., Рахманберди Б.Ж.
«А.Н. Сыз?анов атында?ы Улттык, ?ылыми хирургия орталь™» АК,, Алматы, Казахстан Андатпа
Рубуфин перепараты А.Н. Сызганов атындагы ¥лттык рылыми хирургия орталы^ын отадан кешнп кезецШдеп наукастарда колданылды. 22-55жас аралырындары150 наукас зерттел^.
Ауырсыздандыру ти'мд'шИн келеЫ кврсеткШер бойынша бараланды: артериялдык кан кысымы, тамырсогу жилю, щрек жиырылу жилю, перифериялык к,анда€ы оттепнщ сатурациясы, каннын кышкылды-сштл жагдайы жэне газдык курамы, ауырсынуды багалаудын визуалды-аналогтык шкала-сы. Сонымен катар, Рубуфин препаратынын каннын биохимиялык кврсетюштернщ взгерюте эсерн зерттелШд'!.
Рубуфиндi колдану кез 'шде ауырсыну синдромы 1,5 есеге азаюы, щрек жиырылу жили минутына 95,6±8,8-ден 83,2± 11,7-гедеШнкему'1, тыныс алужи'шмшн минутына 22,4±2,7-ден 16,3±2,1-ге деШн твмендеу'!,орташа артерияды кан кысымынын ауырсыну синдромынын азаюына пропорционалды твмендеу'!, тыныс депрессиясынын болмауы, канда€ы оттепшн кернеуiнiн 109,5±23,4 мм.сын.бар. -нан 112,4± 16,6 мм.сын.баЕ-дейш артуы аныкталды. Рубуфинд колдану кез'шде каннын биохимиялыккврс еткiштерiндевзrерiстер байкалмады.
Осылайша, аукымды хирургиялык араласулардан кеШн орташа жэне айкын ауырсыну синдромы бар пациенттердi ауырсыздандыру кешде жотары ти'мд'ш'Г жэне ауырсыну синдромын жоюта байла-нысты каннын оксигенациясы мен щрект'щ соту квлемiнiн жаксаруы дэлелденд'!.
Оценка безопасности и клинической эффективности лекарственного препарата «Рубуфин» у хирургических больных в послеоперационном периоде
Куандыков Т.К.. Мутагиров В.В., Тунгушбаев А.П., Махатов А.Т., Алиманов Н.А., Шербаев С.Т., Досымбетов К.И., Мусадилов К.Т., Кудайбергенов Е.К., Рахманберди Б.Ж.
АО «Национальный научный центр хирургии им. А.Н. Сызганова», Алматы, Казахстан Аннотация
Препарат рубуфин применяли у пациентов Национального научного центра хирургии им. А.Н. Сызганова в послеоперационном периоде. Исследовано 150 пациентов в возрасте от 22 до 65 лет.
Оценивали эффективность обезболивания по изменению следующих критериев: артериальное давление, пульс, частота сердечных сокращений, сатурация кислорода в периферической крови, газовый состав и кислотно-основное состояние крови и визуально-аналоговая шкала оценки боли. Исследовали влияние рубуфина на изменение биохимических показателей крови.
Выявлено уменьшение болевого синдрома в1,5 раза, урежение частоты сердечных сокращений с 95,6±8,8 до 83,2±11,7 в минуту, частоты дыхания с22,4±2,7 до 16,3±2,1 в минуту, снижение среднего артериального давления пропорционально уменьшению болевого синдрома , отсутствие угнетения дыхания, увеличение напряжения кислорода в крови со 109,5±23,4 ммрт.ст. до112,4±16,6 ммрт.ст., отсутствие изменений биохимических показателей крови при применении рубуфина.
Таким образом, доказана высокая эффективность при обезболивании пациентов с умеренным и сильным болевым синдромом после обширных оперативных вмешательствах, и улучшение показателей оксигенации крови и ударного объема связанные с устранением болевого синдрома.
Ключевые слова
послеоперационная боль, агонисты-антагонисты опиоидных рецепторов, эффективность аналгезии
Backround
All surgical interventions are accompanied by pain syndrome, expressed to one degree or another [1]. Pain causes not only psychological changes in patients, but pronounced dysfunctions of various systems and organs [2]. These changes adversely affect the outcome of the disease, prolong the patient's stay in the hospital and significantly increase the material costs of treatment [7]. Therefore, the pain syndrome must be significantly reduced or eliminated altogether in the postoperative period. Rubufin belongs to opioid analgesics - agonists-antagonists of opioid receptors, which is simultaneously devoid of many side effects of narcotic analgesics (respiratory depression, paresis of the gastrointestinal tract), but is not inferior to them in terms of the strength of the analgesic effect [36]. Therefore, its use is indicated in patients in the postoperative period, when non-narcotic analgesics in most cases are ineffective, and the use of full agonists of opiate receptors is limited due to the risk of severe side effects [8].
The aim of this study was a clinical assessment of effectiveness of analgesia with rubufin in patients with moderate to severe postoperative pain.
Methods
Rubufin was used in one group of 150 patients from the National Scientific Center for Surgery named after A.N. Syzganov in the postoperative period.
To assess the effectiveness of analgesia, the following indicators were determined: blood pressure (systolic, diastolic, mean), pulse, heart rate, oxygen saturation in peripheral blood, gas composition and acid-base state of blood, and a visual analogue scale for assessing pain. On this scale, the level of pain is assessed from 0 points - no pain, to 10 - very severe pain; pain syndrome was assessed at rest and during movement. After the patients received rubufin, the time of the onset of the effect, the duration of effective analgesia, and the amount of the drug that had to be used to achieve effective analgesia were studied.
Hemodynamic parameters (blood pressure, pulse, heart rate) were determined using a Ni-honKohden monitor.
Determination of blood gas, electrolyte composition and acid-base state was carried out with an ABL 800 analyzer (Radiometer).
Blood biochemical parameters were determined with an A15 analyzer (BioSystems).
Coagulogram parameters were determined with a CA-1500 analyzer (Sysmex).
To the data obtained during the study, in addition to descriptive methods, the corresponding statistical comparison methods were applied. Paired t-test and Wilcoxon rank sum test were used for quantitative data. For categorical values, the chi-square test was applied. Additionally, Spearman's correlation coefficient was
determined. The data obtained were processed using the statistical functions of the EXEL 2010 program.
The selected efficacy indicators were determined in the studied patients at several conditional stages (visits) of the postoperative period. Baseline (Stage 1) values were measured before surgery. Stage 2 - after the patient wakes up in the postoperative period. Stage 3 - one hour after rubufin application. If it was necessary to reapply rubufin to achieve effective analgesia, Visit 3 was one hour after re-administration. Stage 4 - 1 postoperative day before using the drug. Stage 5 - one hour after rubufin application on the first postoperative day. Stage 6 and 7, respectively, before and after rubu-fin application on the 2nd postoperative day. Long-term effects of the drug have not been studied.
Results
The study involved 150 patients aged 19 to 73 years, the average age was 48.3 ± 14.2 years. Men
- 18, women - 14.
5 patients underwent gastrectomy, 4 patients -hemihepatectomy, 5 patients - esophageal plastic surgery, 2 patients - gastropancreatoduodenal resection, 6 patients - gastric resection, 10 patients
- cholecystectomy. The nature of the surgical pathology is presented in Table 1.
The physical status of the patients corresponded to ASA class II-IV.
Rubufin was used intramuscularly in 11 patients and intravenously in 21 patients.
Evaluation of the effectiveness
Changes in the studied parameters are expressed as N ± 5 and are presented in tables and figures.
When using rubufin, the following side effects were observed: in three cases (9.4%) severe sweating, in 6 cases (18.8%) nausea, in 3 cases (9.4%) dizziness, drowsiness was observed in 18 cases (56.3%). No serious side effects were observed. The vast majority of side effects were observed in patients with intravenous administration of the drug. When using the drug intramuscularly, the analgesic effect occurred in 48.7 ± 5.4 minutes, with intravenous administration - after 16.3 ± 7.2 minutes (p <0.05). It was also revealed that with the first administration of the drug, the effect occurred after 26.3 ± 13.5 minutes, and with the repeated administration after 13.4 ± 8.2 minutes (p <0.05). The duration of effective analgesia increased with repeated use of rubufin: 272.8 ± 65.3 minutes after the first injection and 487.5 ± 99.6 minutes after the second (p <0.05).
The amount of the drug required for effective analgesia decreased upon repeated injection from 17.7 ± 4.4 mg to 12.3 ± 2.6 mg, respectively (p <0.05).
Studied parameters and its changes highlighted in table 2.
The level of pain syndrome and stress index were significantly increased at the second stage, after the application of rubufin they decreased (Figure 1, 2). At the same time, a high degree of correlation between the level of pain syndrome and the index of myocardial tension r = 0.83 was revealed. The study of hemodynamics of patients showed an increase in blood pressure and heart rate at the second stage of the study, which is associated with an increase in pain. After the application of rubufin, the indicators approached the initial ones (Figure 3). In addition, as the pain syndrome increased, the patients showed a decrease in
Table 1.
Surgical pathology in studied patients
Diagnosis Amount %
Gastric cancer 5 15,63
Esophageal cancer 2 6,25
Liver cancer 4 12,5
Esophageal cicatricial stenosis 3 9,37
Pancreatic cancer 2 6,25
Gastric /duodenal ulcer 6 18,75
Cholelythiasis 10 31,25
Total 32 100
Table2.
Hemodynamics parameters and severity of postoperative pan in studied patients
* - р<0,05 in comparison with baseline stage n - p<0,05 in comparison with previous stage
Parameter / Stage 1 2 3 4 5
APsys (mm Hg) 125,4±38,2 137, 6±22,7* 132,2±36,4*n 122,3±35,8n 124,6±34,6
APdia (mm Hg) 66,8±31,7 69,6±33,2* 71,4 ±28,6 78,3±22,2n 69,1±15,5n
APmean (mm Hg)
HR (min-1) 88,4±15,3 95,6±8,8* 83,2±11,7*n 76,3±18,2*n 71,1 ±10,3*n
CO (l/min) 5,3±1,1 4,8±2,8 5,1±2,2n 4,3±3,1*n 4,7±1,2n
SV (ml) 64,1±3,8 50,2±8,6* 61,3±7,7 n 56,4±7,2*n 66,1±6,3n
Stress Index (U) 119,3±32,2 236,6±18,6* 127,8 ±28,8n 98,6±22,6*n 83,2±19,6n
VAS (score) 1,8±0,8 3,7±1,2* 2,1±0,9n 2,3±1,1* 1,5±1,3n
Figure 1.
Visual analog scale for pain in studied patients
* - p<0,05 in comparison with baseline stage n - p<0,05 in comparison with previous stage
U
250 200 150 100 50
236,6
Figure 2.
Stress index in studied patients
* - p<0,05 in comparison with baseline stage n - p<0,05 in comparison with previous stage
stage
mmHg 150
100
50
125,4
-APsys -APdia -APmean HR
Figure 3.
Hemodynamics parameters in studied patients
* - p<0,05 in comparison with baseline stage n - p<0,05 in comparison with previous stage
stage
mmHg
22 20 18 16 14 12 10
22,4
Figure 4.
Respiratory rate in studied patients.
* - p<0,05 in comparison with baseline stage n - p<0,05 in comparison with previous stage
stage
mmHg
99,5
99 98,5 98 97,5 97
98,5
99,1
98,6
Figure 5.
Blood oxygen saturation in studied patients.
* - p<0,05 in comparison with baseline stage n - p<0,05 in comparison with previous stage
stage
Figure 6.
Oxygen partial pressure in arterial blood in studied patients.
* - р<0,05 in comparison with baseline stage n - p<0,05 in comparison with previous stage
Figure 7.
Carbon dioxide partial pressure in studied patients.
* - р<0,05 in comparison with baseline stage n - p<0,05 in comparison with previous stage
Table 3.
Respiratory and acid-base parameters in studied patients
* - р<0,05 in comparison with baseline stage n - p<0,05 in comparison with previous stage
cardiac output and stroke volume, which increased after anesthesia (Figure 4, 5).
A change in the respiratory rate towards an increase occurred with an increase in the pain syndrome - at the second stage, after anesthesia with rubufin, a decrease in the respiratory rate occurred (Figure 6), however, there was no depression, as evidenced by the gas exchange indices. Blood oxygenation against the background of oxygen inhalation was satisfactory at all stages of the study, but increased after patients were given the painkiller (Figure 7).
The oxygen partial pressure decreased towards the end of the study, which is associated with the cessation of oxygen inhalation. However, with an increase in pain, a slight decrease in oxygen tension in the blood was noted, but after pain was relieved (stage 3), pO2 increases (Figure 8). The correlation dependence of the oxygen partial pressure with blood saturation r = 0.63.
The partial pressure of carbon dioxide in the blood changed in accordance with the change in the respiratory rate - with an increase in RR, the pressure of CO2 in the blood decreased and vice versa (Figure 9).
Changes in blood pH and base deficiency were within the normal range and did not depend on the increase or decrease in pain syndrome. Changes in these indicators, apparently, were caused by therapy aimed at correcting the initial violations of the acid-base state (table 3).
Metabolism in patients was assessed by the change in the parameters of the biochemical blood test, the data are shown in Table 4. all indicators did not undergo significant changes, remaining within the normal range. Hypoproteinemia, which occurs at stage 5, is associated with the metabolic characteristics of the postoperative period during extensive surgical interventions and does not depend on the method and drug of anesthesia.
Safety assessment
When rubufin was used in 18 patients (56.25%), the following side effects were observed: in three cases (9.4%) severe sweating, in 6 cases (18.8%) nausea, in 3 cases (9.4%) dizziness , drowsiness was observed in 18 cases (56.3%). No serious side effects were observed. The vast majority of side effects were observed in patients with intravenous administration of the drug. Side effects. The number and nature of side effects is presented in table 5.
mmHg 113 112 111 110 109 108 107 106 105 104
111,3
112,4
109,5
J 07,4
*П
104,8
stage
mmHg
*
36 34
1 2 3 4 5 stage
Parameter / stage 1 2 3 4 5
RR (min-1) 18,8±3,1 22,4±2,7* 16,3±2,1*п 18,4±1,8п 14,2±1,6*п
рН 7,37 ±0,07 7,41 ±0,1* 7,38±0,09п 7,43±0,07*п 7,4±0,05п
ВЕ (mmol/l) -1,43±0,22 -1,14±0,62* -1,24±0,44* -1,11±0,27*п -1,54±0,25*п
рО2 (mmHg) 111,3 ±33,6 109,5±23,4 112,4±16,6п 107,4 ±18,8*п 104,8±8,9*
рСО2 (mmHg) 42,8±2,6 37,9 ±3,4* 41,2 ±2,1*п 44,1±3,3п 43,4±1,9
SO2 (%) 98,5±3,3 97,8 ±6,1* 99,1±4,2п 98,3±3,7п 98,6±4,1
ВЕСТНИК ХИРУРГИИ КАЗАХСТАНА № 4-2020
44
Parameter / stage 1 5
Glucose (mmol/l) 6,2±1,1 5,6±1,6
Lactate (mmol/l) 1.8±0.07 1.4±0.1
Potassium (mmol/l) 3,8±0,44 4,1±0,8
Sodium (mmol/l) 144,2±38,4 138,7±33,9
Total bilirubin (mcmol/l) 12,6±4,4 14,3±3,2
Total protein (g/l) 64,9±5,2 62,8±8,4*
Creatinine (mcmol/l) 68.0±8.0 72.0±3.0
Adverse effect Intravenous Intramuscular
Amount % Amount %
Nausea 4 12,5 2 6,25*
Dizziness 1 3,125 2 6,25
Sweating 2 6,25 1 3,125
Drowsiness 10 31,25 8 25*
Total: 17 53,1 13 40,6*
Table 4.
Metabolism parameters in studied patients
* - p<0,05 in comparison with baseline stage
Table 5.
Rate of adverse effects in patient treated with rubufin
* - p <0,05 in comparison with intravenous rout
Conclusion
A study of the effectiveness of anesthesia with Rubufin in patients in the postoperative period revealed a fairly high efficacy of this drug with a relatively small number of side effects and insignificant effect on the cardiovascular and respiratory systems. There was a decrease in pain syndrome, myocardial tension index after using rubufin from 236.6 ± 18.6 to 127.8 ± 28.8 units, a decrease in heart rate from 95.6 ± 8.8 to 83.2 ± 11.7 per minute, respiratory rate from 22.4 ± 2.7 to 16.3 ± 2.1 per minute, decrease in mean arterial pressure in proportion to decrease in pain syndrome, increase
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