COMPARATIVE ANALYSIS OF THE KINETICS OF THE ELECTROLYTE COMPOSITION OF THE BLOOD OF PATIENTS DURING IMPLEMENTATION OF DIVERSE PERIOPERATIVE FLUID SUPPLY

COMPARATIVE ANALYSIS OF THE KINETICS OF THE ELECTROLYTE COMPOSITION OF THE BLOOD OF PATIENTS DURING  IMPLEMENTATION OF DIVERSE PERIOPERATIVE FLUID SUPPLY

Girsh A.O., Evseev A.V., Stepanov S.S., Korzhuk M.S., Chernenko S.V., Chumakov P.A., Stukanov M.M., Klementyev A.V.

Omsk State Medical University, Clinical Medical-Surgical Center, Omsk, Russia

One of the tasks of planned perioperative fluid supply is to maintain the normal electrolyte composition of the vascular and extravascular sectors [1]. The solution to this problem is possible only when using polyionic crystalloid solutions [2, 3]. However, to date, there is no evidence of the benefit of any polyionic crystalloid solution used in a routine perioperative fluid management program. An unsolved problem is that the crystalloid solution has not yet been reliably determined, which, when used in the program of perioperative fluid support in patients with planned surgical interventions, does not generate negative changes in the initially uncompromised electrolyte composition of blood plasma. The question of the direction of inspiration of the electrolyte composition of blood on the parameters of plasma hemostasis in patients with heterogeneous perioperative fluid supply remains open.
 In this regard, the objective of this study was a comparative analysis of the kinetics of the electrolyte composition of the blood of patients during the implementation of diverse perioperative fluid supply and its inspiration for hemostasis indicators to locate the best model of volemic correction.

MATERIALS AND METHODS

An open, prospective cohort, randomized (using the envelope method), clinical study included 80 patients (mean age 66.6 (53; 79) years) who underwent planned surgical treatment for total hip arthroplasty. The criteria for inclusion in the study were: 1) hospitalization to a medical institution in a planned manner; 2) the age of patients is from 40 to 80 years; 3) coxarthrosis with pain syndrome, not relieved by conservative therapy, in the history of the disease, leading to functional impairment of the 3rd degree; 4) the presence of absolute indications for surgical treatment; 5) lack of indications for preoperative volemic correction; 6) anesthetic risk no more than class III on the scale of the American Society of Anesthesiologists (ASA). The conditions for exclusion from the survey were: 1) anesthetic risk no more than class III on the ASA scale, 2) treatment with hormonal drugs; 3) oncological diseases; 4) chronic hyperglycemia; 5) the presence of contraindications for spinal epidural anesthesia; 6) non-existence of data for the introduction of blood components in the perioperative period.
All patients were divided into two groups depending on the perioperative fluid supply scheme. The group I (40 patients) received Ringer's solution, the group II (40 patients) - isotonic sterofundin. The body weight of patients in the group I was 88 (45; 100) kg, in the group II - 85 (53; 100) kg. All observed patients had concomitant chronic pathology. Therefore, the anesthetic risk corresponded to class II and III on the ASA scale. Before surgery, all patients underwent antibiotic prophylaxis with first-generation cephalosporins at a dose of 1.5 (1; 2) grams once.
Prior to the operation, no fluid supply was provided to patients in the groups I and II. The volume (9 ml/kg/h) of intraoperative volemic support was calculated on the basis of the data recommended for large-scale surgical interventions [1]. In this regard, the volume of intraoperative volemic supply in the group I was 1,445 (1400; 1500) ml, and in the group II - 1,439 (1300; 1500) ml. Volemic supply in all patients occurred through Vasofix Certo catheter (B. Braun, Germany) with a diameter of 16 or 18 G, installed in the peripheral vein in the operating room, immediately before performing spinal-epidural anesthesia, which was performed using a set of Espokan (B. Braun, Germany). Ropivacaine solution (Fresenius Kabi, Germany) at a dose of 13.8 (10; 17.5) mg was used as an anesthetic. After the injection of anesthetic into the spinal canal, the height of the sensory blockade reached 10-12 thoracic vertebrae. Its severity was assessed using the pin prick test and a cold test. All patients showed the absence of any sensations when the skin was tingling with the needle, and at the same level, the sensitivity to cold disappeared. Motor blockade in all patients corresponded to 3 points on the Bromage scale. The severity of pain during the entire observation period in patients of groups I and II was no more than 2 points on the verbal rating scale, and its complete absence was stated on the visual analogue scale. The operation time, which was carried out after the onset of anesthesia, was 65.3 (55; 90) minutes in group I, and 64.7 (57; 89) minutes in group II. The total volume of intraoperative blood loss in patients of group I was compiled in a volume of 520 (450; 650) ml, and in group II - 530 (450; 670) ml.
After the end of the operation, all patients were admitted to the intensive care unit (ICU), where they received fluid replacement and anticoagulant treatment. Anesthesia was carried out using prolonged epidural administration of ropivacaine solution (Fresenius Kabi, Germany) through Space syringe pump (B. Braun, Germany) at a rate of 4 (2; 6) ml/hour in combination with intramuscular administration of non-narcotic analgesics. The volume of fluid supply in the ICU, which was determined on the basis of indicators of central hemodynamics and laboratory data, in patients of the group I was 1,850 (1,500; 2,000) ml, and in the group II - 1,900 (1,500; 2,500) ml. Diuresis during the stay in  ICU was 1,400 in the group I (1,300; 1,500) ml, and 1,450 (1,300; 1,600) ml in the group II. The total volume of postoperative blood loss in the group I was 200 (150; 300) ml, in the group II - 250 (200; 350) ml. The duration of treatment for patients of the group I in ICU was 16.3 (14; 18) hours, in the group II - 16.2 (14; 18) hours, after which the patients were transferred to the specialized orthopedic department, where symptomatic therapy was continued, and combined (intravenous and oral) fluid intake.
The volume of intravenous fluid supply on the second day of the postoperative period in patients of the group I was 1,400 (1,000; 2,000) ml, and in the group II - 1,500 (1,000, 2,000) ml. At the same time, diuresis in patients of the group I was 1,200 (1,000; 1,300) ml, and in the group II - 1,250 (1,100; 1,300) ml.
Starting from the third day of the postoperative period, the volemic correction was arrested for all patients, and only oral fluid intake was prescribed. Stat Fax 3300 photometer (Awareness Technology, USA) was used to determine the content of potassium (K+, mmol/L), sodium (Na+, mmol/L), chlorine (Cl-, mmol/L), ionized calcium in the venous blood plasma (Ca2+, mmol/L) and magnesium (Mg2+, mmol/L). Coagulometer Sysmex CA-560 (Sysmex, Japan) was used to assess coagulation hemostasis indicators: activated partial thromboplastin time (APTT, sec), international normalized ratio (INR, a.u.) and fibrinogen (g/L). The Easy Blood Gas analyzer (Medica corporation, USA) determined the deficiency/excess of bases in the extracellular fluid (BE ecf., Mmol / L), as well as the deficiency/excess of bases (BEb, mmol/L) in venous blood and its pH (unit). The studies were carried out before the beginning of fluid supply and surgical treatment, as well as 12, 24, 48 and 72 hours after the operation.
Statistical analysis of the research results was carried out using the Statistica 8.0 software (StatSoft, USA). A preliminary assessment of the main statistics to determine methods for testing statistical hypotheses was carried out using the Kolmogorov-Smirnov and Shapiro-Wilk tests. Since the rule of normal distribution of values was not observed for the compared variational series and there was no equality of their variances, the methods of rank (non-parametric) statistics were used. For paired comparison of patients in the study groups, the Mann - Whitney tests (independent samples) and Wilcoxon (dependent samples) were used. Accordingly, multiple comparisons (more than two) were performed using modifications of analysis of variance for rank statistics (ANOVA Kruskal - Wallace and Friedman). The relationship between the independent variables was identified using pair-wise correlation analysis according to Spearman (non-parametric method). In the illustrative graphs, the main statistics were presented in the form of the median (Me, indicator of the central trend), as the lower and upper quartiles (LQ; UQ, indicators of dispersion). In all cases, the null hypothesis was rejected, and the alternative was accepted at a statistical significance level of p < 0.05. In our study, the power was about 0.8, which is sufficient to assess the quantitative results obtained [4].
The study was carried out with the permission of the local bioethical committee of Clinical Medical and Surgical Center, as well as all its participants (on the basis of voluntary informed consent) and complied with ethical standards developed on the basis of the Declaration of Helsinki of the World Medical Association "Ethical Principles for Medical Research Involving Human Subjects" (2013) and the "Rules for Clinical Practice in the Russian Federation" approved by order of the Ministry of Health of the Russian Federation of June 19, 2003, No. 266.

RESULTS

Before the operation and fluid supply, a comparative analysis of patients of groups I and II did not identify the facticity of differences between the exponents of the electrolyte (Fig. 1) and acid-base (Fig. 2a - 2c) compositions, as well as hemostasis (Fig. 2d - 2f) , which, in its turn, stated the authenticity of the cohorts participating in the study. However, the perioperative fluid supply realized in patients of groups I and II determined, according to the results of intergroup comparative analysis, multidirectional kinetics of Cl-, Ca2+, Mg2+ and almost unidirectional K+ and Na+ (Fig. 1a and 1c). In particular, paired comparison with the data before the beginning of fluid supply and surgical treatment and multiple comparisons between the periods in each group revealed true changes in patients of groups I and II in the content of Na+ in blood plasma (Fig.1a). Also, in patients in group II, a reliable difference in plasma Na+ content was recorded at two study points (Fig.1a). In its turn, multiple comparisons between the dates in each group, as opposed to the between-group and pair-wise comparisons, found a significant decrease in plasma K+ in patients of groups I and II (Fig.1c), which was probably associated with the exclusivity of the postoperative process in patients after extensive and traumatic surgical interventions [5].

Figure 1. Indicators of the electrolyte composition of the venous blood of patients of groups I and II: content of sodium (a), chlorine (b), potassium (c), magnesium (d), ionized calcium (e)

Note: ^ – paired comparison with data before fluid supply and surgical treatment (Wilcoxon test), * – between groups (Mann-Whitney test) and multiple comparison between terms in each group (Friedman ANOVA). The null hypothesis was rejected in all cases at p < 0.05.

Also, 12 hours later, patients of the group I showed a steady increase in the content of Cl- (Fig. 1b), which was probably due to the introduction of a solution with augmented Cl- content into the vascular bed of patients [2]. This was confirmed by paired and multiple comparative analyzes (Fig. 1b). It is the escalation of Cl- in the blood plasma of patients that is responsible for the development of negative metabolic changes [6, 7]. Indeed, in parallel with Cl- augmentation in plasma (Fig. 1b) in patients of group I, a true development of metabolic acidosis was recorded (Fig. 2a - 2c). It is known that the evolution of hyperchloremic metabolic acidosis is strongly associated with the escalation of Cl- in the blood plasma of patients [8, 9, 10] as a result of the use of unbalanced solutions in the infusion therapy program [2, 3]. True apophatic kinetics pH (v), BE ecf. and BEb in patients of group I, in relation to identical indicators of patients in group II, were also recorded by an intergroup comparative analysis (Fig. 2a - 2c). The apodicticity of the relationship between the increased content of Cl- and hyperchloremic metabolic acidosis in patients of group I was also stated by the correlation analysis, which recorded the existence of a stable relationship between Cl- and BE ecf. (r = -0.54 at 12 hours after surgery; r = -0.38 at 24 hours after surgery; r = -0.36 at 48 hours after surgery; r = -0.35 at 72 hours after surgery). Simultaneously, in patients of the group I, apodictic relationships were ascertained between pH (v) and BEb (r = 0.33 24 hours after surgery; r = 0.35 48 hours after surgery; r = 0.42 72 hours after surgery), which indicated a close association of Cl- with the exponents of the acid-base state and their simultaneous kinetics.

Figure 2. Indicators of hemostasis and acid-base composition of venous blood in patients of groups I and II: fibrinogen (a), APTT (b), BE ecf. (c), BEb (d), INR (e), pH (f)

 

Note: ^ – paired comparison with data before fluid supply and surgical treatment (Wilcoxon test), * – between groups (Mann-Whitney test) and multiple comparison between terms in each group (Friedman ANOVA). The null hypothesis was rejected in all cases at p < 0.05.

It is important that in patients of group I, as compared with group II, after 24 hours a steady decrease in the content of Mg2 + in blood plasma was recorded (Fig. 1d). The negative dynamics of the Mg2 + content in the blood plasma in patients of group I was also confirmed by the data of paired and multiple comparisons (Fig. 1d). The decrease in the content of Mg2 + in the blood plasma in patients of group I was probably associated with both the peculiarity of the course of the early postoperative period during extensive and traumatic surgical interventions [5], and the absence of this electrolyte content in the composition of Ringer's solution [3]. Moreover, a decrease in the content of magnesium in blood plasma occurs with a decrease in its pH and the occurrence of metabolic acidosis [11]. This was confirmed by the localized and reliable associations in group I patients between Mg2 + and BEb (r = 0.3 at 12 hours after surgery; r = 0.42 at 48 hours after surgery), Mg2 + and pH (v) (r = 0, 37 24 hours after surgery). The condemning kinetics of the quintessence of Mg2+ in blood plasma in patients of the group I was also confirmed by the data of pair-wise and multiple comparisons (Fig.1d). In addition, there is a stable context between the concentrations in blood plasma of Mg2+ and Ca2+ [11], which has a simplex mechanism, which is that when the content of one ion decreases, the other increases [12]. This factuality in patients of the group I was confirmed by the localized true relationship between Mg2+ and Ca2+ (r = -0.38 72 hours after surgery).
Indeed, in patients of the group I during the entire observation period, compared with patients in group II, a true increase in plasma Ca2+ was recorded (Fig. 1e), which was associated with both a decrease in the content of Mg2+ in blood plasma [11] and the development of metabolic acidosis [13]. It is a decrease in blood pH that induces an increase in Ca2+ content in it [14, 15]. This was also evidenced by the true contexts between Ca2+ and pH (v) found in patients of group I (r = -0.44 after 24 hours; r = -0.3 after 72 hours). The steady increasing dynamics of the Ca2+ content in the plasma of patients in the group I during the entire observation period was also confirmed by the results of paired and multiple comparisons (Fig. 1e). It was also important that in group I, synchronously with an increase in Ca2+ content (Fig. 1e), a reliable decrease in APTT (Fig. 2d) was ascertained according to the data of paired and multiple comparisons. Moreover, the kinetics of APTT in patients in the group I was true in relation to those in patients in the group II (Fig.2d). An increase in the hemostatic potential of blood in patients of group I was probably associated with an increase in plasma Ca2+, which, as a coagulation factor, participates in the mechanisms of the primary and secondary components of the hemostatic system, as well as in all phases of blood coagulation [16]. This was also evidenced by the reliable associations between Ca2+ and APTT (r = -0.39 12 hours after surgery; r = -0.39 24 hours after surgery; r = -0.33 48 hours after surgery; r = -0.35 72 hours after surgery).
According to the data of paired and multiple comparative analyzes, the patients of the group I showed a genuine increase in the content of fibrinogen (Fig.2e) and a decrease in INR (Fig.2f) in the blood plasma during the entire observation period. In addition, in patients of group I, after 48 and 72 hours, a stable difference in the content of fibrinogen (Fig. 2e) and INR (Fig. 2f) was recorded, in comparison with the identical data in group II. Undoubtedly, an increase in the activity of the blood coagulation system was associated with an increased plasma concentration of Ca2+, which is involved in all phases of blood coagulation [16]. This was also stated by correlation analysis, which recorded reliable associations between Ca2+ and INR (r = -0.33 48 hours after surgery; r = -0.35 72 hours after surgery). In addition, the recorded true context between INR and fibrinogen (r = 0.33 48 hours after surgery; r = 0.36 72 hours after surgery) indicated a direct relationship between the exponents of hemostasis. It is precisely the activation of the hemostatic potential of the blood, artificially created as a result of operational stress [5] and the use of Ringer's solution, that can increase the likelihood of postoperative thromboembolic complications in patients that affect outcomes.

CONCLUSION

1. The use of Ringer's solution in the scheme of perioperative fluid supply causes an increase in the plasma Cl- content in patients, initiating the development of metabolic acidosis, which causes a decrease in Mg2+ and an increase in Ca2+ in the blood, which are responsible for an increase in the hemostatic potential of the blood.
2. The use of isotonic sterofundin in perioperative volemic correction does not have a significant negative initiation on the exponents of hemostasis, electrolyte and acid-base composition of blood.

 Information on funding and conflicts of interest

The study was not sponsored.
The authors declare no obvious and potential conflicts of interest related to the publication of this article.

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