EFFECT OF STRESS-PROTECTIVE THERAPY ON THE CIRCADIAN RHYTHM OF TOTAL PERIPHERAL VASCULAR RESISTANCE IN PATIENTS WITH SEVERE COMBINED TRAUMATIC BRAIN

SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 190 EFFECT OF STRESS-PROTECTIVE THERAPY ON THE CIRCADIAN RHYTHM OF TOTAL PERIPHERAL VASCULAR RESISTANCE IN PATIENTS WITH SEVERE COMBINED TRAUMATIC BRAIN Kh.N. Mukhitdinova1, A.Y. Shomurodov2 Center for Professional Development of Medical Personnel, Professor, Department of Anesthesiology and Intensive Care, Pediatrics1 Anesthesiologist-Intensivist, Children’s Surgical Clinical Hospital N.2, Tashkent2 https://doi.org/10.5281/zenodo.17844559 Abstract. A comparative analysis of the average parameters of the circadian rhythm of total peripheral vascular resistance (TPVR) in the acute period of severe combined traumatic brain injury (STBI) in children over 7 years old revealed no significant differences. During stressprotective pharmacological treatment, a wave-like change in total peripheral vascular resistance (TPVR) was noted, more pronounced in children of Group 1, within the range of 1200–1700 dyn·s·cm⁻⁵ during the first 17 days, following an approximately weekly rhythm. In Group 2, fluctuations in TPVR during the first ten days occurred within 700–1100 dyn·s·cm⁻⁵. Variations in the amplitude of the circadian rhythm of TPVR indicated somewhat more pronounced centralization of blood circulation on day 1 in children of Group 2. A near-weekly rhythm in changes of TPVR circadian rhythm amplitude was observed in both groups. In both groups, an inverse correlation between TPVR and cardiac output (CO) was identified: in Group 1 (-0.8), in Group 2 (-0.9), characteristic of a stress response involving hyperdynamic hemodynamic adaptation. Keywords: stress-limiting therapy, circadian rhythm of total peripheral vascular resistance, children, severe combined traumatic brain injury. Introduction. Disruption of circadian rhythms has become more common in society due to the increasing number of shift workers, sleep disturbances, exposure to blue light, and travel across time zones. Severe combined trauma (SCT) is the most dangerous type of injury, characterized by prolonged disability with a high level of impairment and mortality, ten times higher than that of isolated injuries. Autonomic regulation disorders are among the leading, and often the only, clinical manifestations in both the acute and long-term periods of mild traumatic brain injury. Systemic consequences of traumatic brain injury manifest as extracranial multi-organ dysfunction (MOD), which occurs in over 68% of patients with moderate to severe TBI within the first 72 hours of hospitalization. Dysfunction of extracranial organs can create a vicious cycle that exacerbates further brain injury. Autonomic dysfunction has been shown to be an important factor in the development of MOD after TBI, particularly in severe cases. This dysfunction triggers a cascade of physiological disturbances affecting multiple extracranial organ systems, including the respiratory, cardiovascular, renal, and coagulation systems. The development of traumatic brain disease is accompanied not only by structuralfunctional changes in the CNS but also by a complex of pathophysiological shifts occurring in nearly all organs and systems of the body. It has been established that the reorganization of SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 191 functional regulatory mechanisms during stress depends on the individual typological characteristics of the child, with the sympathectomy type of autonomic regulation being the least adaptive, leading to a less favorable prognosis for recovery of organ and system function. Using a systems approach, typological features of the interaction of homeostatic mechanisms in blood flow, hematopoiesis, immunity, and hemostasis have been studied in schoolage children. Previous studies by the authors confirmed that the severity of brain injury affects the hemodynamic state in children with STBI. A characteristic feature of shock in pediatric SCT is a tendency for rapid shifts from hemodynamic compensation to decompensation and deepening of shock. Experimental evidence shows that severe TBI is accompanied by depressed myocardial contractility and increased myocardial dependence on oxygen and glucose, likely related to pathogenic factors such as hypoxia, bioenergetic dysfunction, oxidative stress, and Ca²⁺ imbalance. However, there is still insufficient information regarding changes in myocardial oxygen demand, disruption of the circadian rhythm of myocardial oxygen demand (MOD), and cardiac function in compensatory hemodynamic responses in children with STBI. The pathogenetic and etiological roles of cardiac function disorders in the development of multi-organ failure syndrome (MOFS) remain poorly understood, significantly complicating the development of comprehensive intensive therapy for this patient population. Objective. To study the influence of stress-protective therapy on the circadian rhythm of total peripheral vascular resistance (TPVR) in children over 7 years old with severe combined traumatic brain injury (sTBI). Materials and Methods. The study included 20 children aged 7.1 to 18 years who were treated in the Pediatric Intensive Care Unit (PICU) of the Republican Scientific Center for Emergency Medical Care (RSCEMC) at the 2nd Children’s Clinical Hospital in Tashkent. Group 1 consisted of children admitted between 2018 and 2022. Group 2 included children with STBI admitted between 2023 and 2024. Upon admission to the ICU, all patients underwent a comprehensive diagnostic assessment, including biochemical blood analysis and complete blood count, evaluation of coagulation potential, and, as indicated, chest X-rays and X-rays of fracture sites. All patients underwent computed tomography (CT) of the head. Non-invasive continuous monitoring with hourly registration of parameters in the ICU included measurement of blood oxygen saturation, heart rate (HR), and mean arterial pressure (MAP). Parameters of central hemodynamics were also measured. The primary goal of intensive therapy in severe TBI was to support compromised vital functions and create conditions for the maximal possible recovery of brain function. During 2018-2022, components of intensive complex therapy were studied in 10 children (Group 1) aged 7.1–18 years. A comparative analysis was conducted with a similar group of 10 children (Group 2) in 2023–2024, matched for diagnosis, age, and severity of condition. Data were processed using variation statistics with Microsoft Excel by calculating arithmetic means (M) and standard errors of the mean (m). To assess the significance of differences between two values, the student’s t-test was used. Relationships between the dynamics of the studied parameters were determined using the method of paired correlations. The critical significance level was set at 0.05. Results and Discussion. Comparative analysis of the average parameters of the circadian rhythm of TPVR in the acute period of STBI in children over 7 years revealed no significant differences (Table 1). SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 192 Table 1. Average values of the phase structure of the circadian rhythm of TPVR (dyn·s·cm⁻⁵) Groups Mesor | In acrophase Bathyphase | Amplitude Daily Range 1 1300±132 1762±286 1008±126 462±203 754±282 2 1073±115 1486±276 823±64 413±215 663±272 Table 2. Dynamics of the mesor of the circadian rhythm of TPVR (dyn·s·cm⁻⁵) Table 3. Average circadian rhythm of TPVR (dyn·s·cm⁻⁵) Hours Group 1 Group 2 8 1300±210 1033±152 9 1309±179 1042±165 10 1264±185 1053±132 1 1271±191 1043±163 12 1260±205 1055±175 13 1325±263 1098±210 14 1355±298 1077±164 15 1326±244 1022±156 16 1215±169 1030±166 17 1267±176 1042±134 18 1376±273 1108±170 19 1355±199 1109±181 20 1310±205 1102±178 21 1309±213 1062±167 22 1271±173 1081±156 23 1286±142 1038±121 24 1307±123 1114±182 1 1276±155 1067±191 2 1294±147 1105±204 3 1335±194 1103±165 4 1359±182 1061±158 5 1296±162 1123±145 6 1263±167 1094±196 7 1281±199 1089±191 SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 193 A tendency for an increase in TPVR was observed on the first day in traumatized children of Group 1 (Table 2). In the following days, a wave-like change in TPVR was noted, more pronounced in children of Group 1, ranging from 1200–1700 dyn·s·cm⁻⁵ during the first 17 days, following an approximately weekly rhythm. In Group 2, TPVR fluctuations during the first ten days ranged from 700–1100 dyn·s·cm⁻⁵. However, no statistically significant dynamics of the mesor of the TPVR circadian rhythm were detected in either group of patients (Figure 1). Figure 1. Dynamics of the mesor of the TPVR circadian rhythm (dyn·s·cm⁻⁵) Days Group 1 Group 2 1 1760±501 1001±281 2 1214±79 755±78 3 1196±63 843±67 4 1265±73 940±60 5 1387±69 1055±63 6 1340±56 1015±106 7 1313±52 1005±78 8 1189±72 1116±169 9 1602±177 1011±92 10 1223±81 1083±150 11 1280±125 1056±138 12 1379±140 978±80 13 1541±140 944±108 14 1575±152 1037±92 15 1219±90 989±103 16 1189±134 951±64 17 1287±119 1010±104 18 1603±295 999±88 19 1125±102 1108±96 20 1252±145 1175±123 21 1294±189 1290±212 22 1070±138 1336±165 23 1201±133 1125±149 24 1058±97 1354±252 25 1250±189 1169±147 26 1296±278 983±97 27 1038±136 1346±194 28 1144±185 1192±185 29 1422±232 1240±97 SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 194 Figure 2. Average circadian rhythm of TPVR (dyn·s·cm⁻⁵) Fluctuations in TPVR within the average circadian rhythm occurred in Group 1 within the range of 1210–1370 dyn·s·cm⁻⁵, and in Group 2 at the level of 1020–1120 dyn·s·cm⁻⁵. Thus, the difference in the mesors of the TPVR circadian rhythm, depending on the type of pharmacological protection, was approximately 300 dyn·s·cm⁻⁵, indicating more effective correction in patients of Group 2. Figure 3. Amplitude of TPVR fluctuations in the circadian rhythm (dyn·s·cm⁻⁵) Fluctuations in the amplitude of the TPVR circadian rhythm indicated a somewhat more pronounced centralization of blood circulation on day 1 in children of Group 2. A near-weekly rhythm in changes of TPVR circadian rhythm amplitude was observed in both groups (Figure 3). Figure 4. Dynamics of the daily range of TPVR changes (dyn·s·cm⁻⁵) SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 195 This is confirmed by the dynamics of daily TPVR fluctuations in a near-weekly rhythm (Figure 4) in both groups of children. In both groups, an inverse correlation between TPVR and cardiac output (CO) was observed: -0.8 in Group 1 and -0.9 in Group 2, characteristic of a stressinduced hyperdynamic hemodynamic response. However, the tendency in Group 1 for stroke volume (SV) to decrease with increasing TPVR (-0.7) was less pronounced in Group 2 (-0.5). In Group 1, increases in diastolic arterial pressure (DAP) corresponded to increases in TPVR (0.8), along with simultaneous increases in systolic arterial pressure (SAP) (0.7). An increase in anti-inflammatory therapy was associated with a decrease in TPVR (-0.9). In children, the tendency for TPVR to decrease was also influenced by an increase in daily infusion volume (- 0.4), mainly via the enteral route (-0.5). Figure 5. Duration of inversion of the TPVR circadian rhythm No significant differences were found in the duration of inversion of the TPVR circadian rhythm, which was 43% in Group 1 and 46% in Group 2 of the total duration of intensive therapy in the ICU (Figure 5). Conclusion. Comparative analysis of the average parameters of the TPVR circadian rhythm in the acute period of STBI in children over 7 years revealed no significant differences. During stress-protective pharmacological therapy, a wave-like change in TPVR was observed, more pronounced in children of Group 1, ranging from 1200–1700 dyn·s·cm⁻⁵ during the first 17 days, following an approximately weekly rhythm. In Group 2, TPVR fluctuations during the first ten days ranged from 700–1100 dyn·s·cm⁻⁵. 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