Ocena wpływu płynoterapii na dynamikę wskaźników wyrównania równowagi kwasowo-zasadowej u chorych z ostrym udarem niedokrwiennym
Andrii I. Semenenko1, Galina I. Hrebtiy2, Natalia A. Semenenko1, Svetlana L. Malyk1, Dmytro V. Dmytriiev1, Roksolana Ya. Bodnar3, Mykola G. Hinhuliak2, Oleksandr V. Marchuk1
1NATIONAL PIROGOV MEMORIAL MEDICAL UNIVERSITY, VINNYTSYA, UKRAINE
2HIGHER EDUCATION INSTITUTION IN UKRAINE “BUKOVINIAN STATE MEDICAL UNIVERSITY”, CHERNIVTSI, UKRAINE
3HORBACHEVSKY TERNOPIL STATE MEDICAL UNIVERSITY, TERNOPIL, UKRAINE
Introduction: The problem of the influence of infusion solutions on the correction of acid alkaline balance disorders in acute ischemic stroke (AIS) remains unclear.
The aim: Compare the dynamics of changes acid alkaline balance (AAB) in the application of isosmolar 0.9% NaCl solution and hyperosmolar solution of mannitol in patients with acute ischemic stroke.
Materials and methods: The study included 50 patients with AIS. As the investigated solutions were used: hyperosmolar mannitol 15% and isosmolar 0.9% NaCl. The control group received only 0.9% NaCl, compared with main group of 0.9% NaCl+mannitol. The research was carried out at 1, 4 and 7 day, a number of indicators were determined: рН, РаО2, РаСО2, АВ, SB, ВВ, ВЕ.
Results: The conducted research showed that in all observation groups, on 1st day, manifestations of mixed acidosis were observed. On the 7th day of observation the group of 0.9% NaCl showed results close to the norm of the studied parameters, indicating the leveling of acidosis developed in this group on the 1st day of stroke. Somewhat worse correction of metabolic acidosis was in the group of mannitol, on the 7th day of observation the manifestations of acidosis were not significantly different from the 1st day and were respectively: pH = 7.33 (7.24; 7.36); pO2 = 36 (33; 39); AB = 23 (15; 26); BE = -3.4 (-13.5, 0.2), SB = 22.9 (18.0, 25.4).
Conclusions: Analysis of changes in the parameters of AAB in the application of different circuits of infusion therapy in patients with acute ischemic stroke showed that all the observation groups had manifestations of metabolic acidosis on the first day of AIS. The ability to normalize the disturbances of acid alkaline balance did not differ significantly (p>0.05) for patients of group 0.9% NaCl solution and mannitol.
Wiad Lek 2018, 71, 7, -1322
Stroke is the third leading cause of death and the most common cause of disability in the world [1, 2]. The proven modern method of treating acute ischemic stroke is thrombolytic therapy and thrombectomy. The selection of patients with thrombolysis requires rigorous criteria, therefore, this method of treatment is used in only about 10% of patients with GI [3, 4, 5]. The treatment of patients with AIS should take into account the multiplicity of the pathogenesis of ischemic damage to the brain pharmacological correction which should simultaneously include the effect on the main pathogenetic links of ischemia (decrease in blood flow, violation of acid alkaline balance (AAB), imbalance in energy processes, etc., which can be ensured conducting adequate infusion therapy [2, 6, 7, 8]. Infusion therapy is a fundamental component of intensive care of patients with AIS. The question of infusion therapy in patients with GIH is still not resolved in particular, such as: optimal composition, volume, choice and dose of drugs, qualitative composition of solutions. To date, there is a very limited number of clear guidelines for infusion therapy as part of the intensive care of patients with AIS . One of the main component of cerebroprotective therapy in conditions of acute cerebrovascular accident (ACA) ischemic type is its ability to prevent development and to level off manifestations of AAB violations that always accompany a severe stroke .
The problem of the influence of the main infusion solutions used in the treatment of AIS on the correction of AAB disorders in acute cerebral ischemia remains unclear. Therefore, it was interesting to investigate the effect of infusion therapy on the dynamics of these changes in the background of treatment with individual infusion solutions.
Compare the dynamics of changes acid alkaline balance (AAB) in the application of isosmolar 0.9% NaCl solution and hyperosmolar solution of mannitol in patients with acute ischemic stroke.
Materials and methods
The study included 50 patients with AIS (non-differentiated by pathogenetic subtype). Randomization was performed using random numbers. The average age of patients was 71.84 ± 1.67 years, of which 28 were men and 22 women. The study included patients whose body weight did not exceed 120 kg. The study groups did not differ in age composition, severity of disease and other outcomes that could affect the final results of the study.
Diagnosis of acute ischemic stroke was established on the basis of computer tomography data. The main criterion for the selection of patients was the presence of AIS in patients and disturbances of consciousness on a scale of Glasgow 12 points and below, but not less than 4 points at admission (average was 12 points).
An isosmolar 0.9% NaCl solution in 1 ml as a crystalloid base contains sodium chloride 0.009 g, theoretical osmolarity is 308 mosmol/l.
A hyperosmolyar solution is mannitol 15% (mannitol) – hyperosmolyar crystalloid solution contains 1000 ml of mannitol solution 150 g, auxiliary substances: sodium chloride – 9 g, water for injections to 1 liter, theoretical osmolarity – 1131 mosmol/l.
Patients with AIS were divided into 2 groups: 0.9% NaCl group (25 patients): patients receiving 0.9% of NaCl in addition to baseline therapy for 7 days; group of mannitol (25 patients): patients who received 0.9% NaCl + mannitol (main or comparison group) in addition to baseline therapy for 7 days.
Infusion solutions were injected intravenously (i/v) at a dose of 2.5 ml/kg at a frequency of 2 times a day; infusion was started immediately upon confirmation of the diagnosis, and then every other day every 12 hours during 7 days. The control group patients received only 0.9% NaCl from infusion solutions were taken, the comparison group patients received 0.9% NaCl+mannitol. The comparison group received not only the test solution at a fixed dose, but also a 0.9% solution NaCl, as, in general, to refuse this solution is impossible. The amount of 0.9% NaCl and the daily volume of infusion (i/v) in each study group did not differ significantly. The total volume of intravenous infusion per day amounted to an average of 1000 [800; 1300]. Basic therapy was determined according to the Order of the Ministry of Health of Ukraine dated 03.08.2012 № 602.
The research was carried out on 1, 4 and 7 day with help of using the analyzer of the acid alkaline balance of the company «Medica Easy Stat USA», which allowed to obtain a number of indicators: pH, PaО2, PaСО2, АВ, SB, ВВ, ВЕ.
Statistical processing of the results was carried out using methods of variation statistic and using a program StatSoft «Statistica» v. 6.0. The parametric criterion t Student was used for normal distribution, the non-parametric Mann-Whitney U test, was used – in its absence, the Wilcoxon matched pairs test – to determine significant changes in the dynamics of inside the group. The statistical significance of the difference between the comparative values was considered probable at p<0.05.
The conducted study showed that in all observation groups, on 1st day, manifestations of mixed acidosis (metabolic and respiratory) were observed. Thus, in the group of patients 0.9% NaCl, the pH value was within 7 days of treatment on average in the range of 7.33-7.35 (p> 0.05) with the norm of this indicator 7.33-7.43 for venous blood. Patients in the main group have a similar pattern of acidosis during 7 days of intensive care, so the average pH was within 7.32-7.33 (p>0.05).
When conducting an intergroup analysis of changes in the pH index, it should be noted that there is no statistically significant change in this indicator over the entire observation period (p>0.05).
Investigation of the respiratory component of AAB – PaCO2 (the norm in venous blood is 46-58 mm Hg) showed that in the group of 0.9% of NаСl, the comparison of this indicator on 1, 4 and 7 day did not show a significant difference in the background of seven-day treatment (p>0.05). At the same time, the use of mannitol in patients with AIS contributed to the probable growth of PaCO2 from 42.7 (41.5, 49.2) for 1 day to 48.4 (42.9; 49.6) for 4 days (p=0.04) But on the 7th day, this indicator dropped to 42.2 (36.6; 45.6), which, in comparison with the first day, did not have a reliable value p=1.00. The intergroup analysis of changes PaCO2 did not show significant intergroup differencesin all observation periods.
The analysis of changes PaO2 showed in the group receiving only 0.9% NaCl a significant decrease in the residual oxygen in the venous blood from day 1 to day 4 from 39 (32; 45) to 23 (21; 29) p=0.008 at normal PaO2 in venous blood 37-42 mm Hg Comparing the 1st and 7th days, the decrease in PaO2 is also noted to 35 (32; 38), but the decrease of this indicator is unreliable p=0.64, since from 4 to 7 days there is a significant increase of PaO2 from 23 (21; 29 ) to 35 (32; 38) p=0.01, but despite this, PaO2 remained below the norm. A similar dynamics, though not reliable, was observed in the decrease of PaO2 in the group with mannitol: for the 1 st day, the studied index was 39 (29; 44), compared with the 7th 36 (33; 39), p=0.12.
Analysis of the level of AB (norm 24-28 mmol/l) in the blood of patients showed that in the 0.9% NaCl group, this figure was lower than normal, and amounted to an average of 22 (18; 23) mmol/L in the 4th day of treatment, but the statistical significance of this decrease is not enough (p>0,05). A similar picture of lowering AB below the norm was observed in the group of mannitol on 1 and 7 days on average: 21 (18; 24) and 23 (15; 26) mmol/l, but also without reliable confirmation.
A group of 0.9% NaCl showed an identical dynamics of changes in the SB index (norm 24-28 mmol/l), as well as AB. The SB score for the entire duration of the observation was lower than the norm, and at the 4th day of treatment, although not significantly, but decreased to 18.8 (18.7; 18.9) mmol/l compared with the first day (p=0.17). A similar pattern of changes SB was observed in the group of mannitol, for example, for the 1 st day of treatment, the average rate was 21.3 (18.5, 22.6), and for 4 and 7 days: 22.3 (19.8; 24.0) and 22.9 (18.0; 25.4), which is also below the norm, but also without a probable difference. Intergroup statistical analysis of the AB and SB rates for the entire observation period did not show a reliable intergroup difference between these indicators, although the unreliable changes between the groups were clearly followed.
The study of surplus buffer bases in two groups (BE-norm -3.0 to +3.0). Also reflects metabolic changes in AAB. The analysis of this indicator showed that the 0.9% NaCl group had a probable reduction in BE from 1 to 4 days, respectively (-2.0 (-9.3; -1.4) to -4.9 (-8.3; -3.9) p=0.03, which may indicate a deepening of metabolic shifts in the sour side. However, against the background of seven-day complex treatment, BE at the 7th day of observation -2.1 (-2.9; -1.9) are returned almost to the output of -2.0 (-9.3; -1.4) in the 1st day, p=1.00. Statistical analysis of the mannitol group showed no significant difference between the days of observation in BE. In the 1st day of treatment BE index was -5.5 (-9.8; -2.0), and on the 7th day -3.4 (-13.5; 0.2) p=0.38, which is beter than previous and exclusion of metabolic acidosis in patients of this group. Intergroup statistical analysis indicator BE showed no significant difference between groups in 1st and 7th day of observation (p>0.05).
One of the effective methods of treatment the negative changes AAB in patients with AIS is conducting effective infusion therapy. Proper infusion therapy is the appointment of effective solutions in appropriate doses and regimens and is one of the main components of the successful treatment of these patients .
The statistical analysis of changes AAB against the background of various infusion therapy regimens in patients with AIS has shown that in all observation groups, on the first day, manifestations of metabolic acidosis, characteristic of patients with acute cerebral ischemia were noted. According to the literature , minor changes in PaCO2 and PaO2 in the blood significantly affect the state of cerebral hemodynamics, in particular along with spasm of cerebral arteries, which occurs on the background of veno dilatation, may result in cerebral edema. Analysis of changes in PaO2 in the 0.9% NaCl group showed a significant decrease (p=0.008), which we believe is evidence of its excessive utilization as a compensatory manifestation due to the development of cell hypoxia. The results of our studies indicate that, with the use of both solutions, a decrease PaO2 over the entire treatment period is observed, which may be the basis for the formation of hypoxic edema of the brain. When dehydrated, the human body can not produce enough bicarbonates and it can provoke the occurrence of metabolic acidosis, which in our opinion, is more observed in the application of mannitol.
The same vector of change pH and BE (both shifted to the sour side) is a sign of the metabolic disturbances of AAB. Appropriate changes were observed in both groups at the start of AIS treatment. In favor of the fact that AIS is accompanied by the development of metabolic acidosis, indicated a probable decrease in the first day of treatment in two groups of concentrations of buffer bases AB and SB. It should be noted that the blood pH is constant and the fluctuation of this index by only 0.2 units in either direction can lead to destructive changes in the neurons (induction of neuronecrosis, neuroapoptosis, lipid peroxidation, protein oxidation modification, apoptosis, etc.) . The therapeutic effect of 0.9% solution of NaCl and mannitol in the study of AAB, is consistent with our previously obtained data on the effect on the dynamics of NSE activity [7, 8]. Thus, the administration of only 0.9% NaCl did not contribute to the implementation of neuroprotective bases during treatment, as well as the introduction of mannitol, which was accompanied by constant values of hyperactivity marker neurodegradation [7, 8]. In our opinion, this dynamics of shifts on the background of the administration of 0.9% NaCl and mannitol solution indicates the failure of the investigated solutions to reliably restore the balance of acid alkaline balance in patients with AIS and inhibit the development of necrotic processes of the brain.
1. Analysis of the changes of acid alkaline balance equilibrium indices in the application of different circuits of infusion therapy in patients with acute ischemic stroke has shown that in all observation groups, on the first day, manifestations of metabolic acidosis were observed.
2. By the ability to normalize disturbances of the acid alkaline balance that arise in patients with AIS, 0.9% NaCl and mannitol groups did not significantly differ from each other (p>0.05), although according to some indicators, namely, BE group 0.9% NaCl proved to be significantly better than that of the mannitol group.
3. Intergroup statistical analysis of the acid alkaline balance showed no statistically significant differences between the groups (p>0,05), which is the basis for the study of the protective effect of other infusion drugs of other groups and combinations in acute ischemic stroke with the aim of effective correction of metabolic disorders in patients with AIS.
2. Eskes, G.A., Lanctôt, K.L., Herrmann, N., Lindsay, P., Bayley, M., Bouvier, L., Dawson, D., Egi, S., Gilchrist, E., Green, T., Gubitz, G., Hill, M.D., Hopper, T., Khan, A., King, A., Kirton, A., Moorhouse, P., Smith, E.E., Green, J., Foley, N., Salter, K., Swartz, R.H. (2015). Canadian Stroke Best Practice Recommendations: Mood, Cognition and Fatigue Following Stroke Practices Guidelines, update 2015. Int. J. Stroke, (29):1-356.
3. García-Pastor, A., Díaz-Otero, F., Funes-Molina, C., Benito-Conde, B., Grandes-Velasco, S., Sobrino-García, P., Vázquez-Alén, P., Fernández-Bullido, Y., Villanueva-Osorio, J.A., Gil-Núñez, A. (2015). Tissue Plasminogen Activator for Acute Ischemic Stroke: The calculation of the dose based on the estimated patient’s weight can increase the risk of cerebral bleeding. J. Thromb. Thrombolysis, (21):1228-1230.
4. Brodoehl, S., Günther, A., Witte, O.W., Klingner, C.M. (2015). How to manage thrombolysis interruptions in acute stroke? Clin. Neuropharmacol, 38 (3):85-88.
5. Tsivgoulis, G., Sharma, V.K., Mikulik, R., Krogias, C., Haršány, M., Bavarsad Shahripour, R., Athanasiadis, D., Teoh, H.L., Piperidou, C., Alexandrov, A.V. (2014). Intravenous thrombolysis for acute ischemic stroke occurring during hospitalization for transient ischemic attack. Int. J. Stroke, 9 (4):413-418.
6. Oddo, M., Poole, D., Helbok, R., Meyfroidt, G., Stocchetti, N., Bouzat, P., Cecconi, M., Geeraerts, T., Martin-Loeches, I., Quintard, H., Taccone, F.S., Geocadin, R.G., Hemphill, C., Ichai, C., Menon, D., Payen, J.F., Perner, A., Smith, M., Suarez, J., Videtta, W., Zanier, E.R., Citerio, G. (2018). Fluid therapy in neurointensive care patients: ESICM consensus and clinical practice recommendations. Intensive Care Med, Mar 2. doi: 10.1007/s00134-018-5086-z.
7. Semenenko, A.I. (2013). Dynamika aktyvnosti neiron-spetsyfichnoi enolazy ta vmistu bilka S 100 u krovi schuriv za umov hostroho porushennia mozkovoho krovoobihu ta kursovoho vvedennia 0,9 % rozchynu NaCl [Dynamics of activity of neuron-specific enolase and the content of S100 protein in blood of rats in conditions of acute cerebrovascular accident and course administration of 0.9% NaCl]. Farmakolohiia ta likarska toksykolohiia, 6 (36):9-13.
8. Semenenko, A.I. (2016). Aktyvnist neyron-spetsyfichnoi enolazy u patsientiv z hostrym ishemichnym insultom na foni korektsii infuziinymy rozchynamy [Activity of the neuron-specific enolase in patients with acute ischemic stroke on the background of correction of infusion solutions]. Bil, znebolennia i intensyvna terapiia, 4 (77):52-58.
9. Troshin, V.D. Brovkov, N.N (2010). Neotlozhnaya kardionevrologiya [Urgent cardioneurology]. Moscow: Medical News Agency.
According to the order of the Authorship
Conflict of interest:
The Authors declare no conflict of interest
Andrii I. Semenenko
Pirogov Vinnitsa National Medical University,