1. Introduction

In severe traumatic brain injury (TBI), mean arterial pressure (MAP) must be maintained above 90 mmHg to ensure adequate cerebral perfusion pressure (CPP) and prevent cerebral ischemia and neuronal death, as autoregulatory mechanisms are impaired and cerebral blood flow becomes directly dependent on systemic arterial pressure [5,4,6]. Correction of arterial hypotension in patients with severe TBI should be performed based on comprehensive assessment of all hemodynamic components, taking into account the individual variability of changes at different stages of the disease. Some authors recommend maintaining MAP not lower than 80 mmHg [1,2,6]. To achieve target arterial pressure levels, various infusion solutions, vasopressor agents, inotropic drugs, or their combinations are used. However, irrational administration of vasopressors may lead to adverse effects associated with excessive vasoconstriction and impaired microcirculation, while excessive infusion therapy may result in pulmonary, intestinal, and systemic edema [4,6]. According to published data, normal MAP values in children are age-dependent: 73–77 mmHg at 3–7 years and 80–86 mmHg at 8–15 years. When adjusted for age, the mean MAP in healthy pediatric populations is approximately 79 ± 4 mmHg [2,3].

Objective

To investigate and evaluate alterations in the circadian rhythm of mean arterial pressure in children with severe combined traumatic brain injury (SCTBI).

2. Materials and Methods

A comparative cohort study was conducted based on monitoring data of pediatric patients aged 3–18 years treated for severe combined traumatic brain injury (SCTBI) at the Republican Scientific Center for Emergency Medical Care between 2016–2021 (Group 1) and 2022–2024 (Group 2). In Group 1, injuries were primarily caused by road traffic accidents (n=23) and falls from height (n=11), whereas in Group 2 road traffic accidents accounted for 32 cases and falls (catatrauma) for 5 cases. In both cohorts, patients were stratified into three subgroups according to treatment strategy: Subgroup 1 included patients managed conservatively due to absence of surgical indications; Subgroup 2 comprised patients who underwent extracranial corrective surgical procedures within the first hours after admission; and Subgroup 3 included patients who received combined cranial and extracranial surgical interventions within the first 24 hours with multidisciplinary involvement. In Group 1, 13 patients received conservative therapy, 16 underwent extracranial surgery, and 8 underwent combined procedures; identical subgroup distributions were observed in Group 2 (13, 16, and 8 patients, respectively). No statistically significant differences in age distribution were identified between groups. A slight predominance of male patients was observed across most subgroups. There were no significant differences in injury severity or Glasgow Coma Scale (GCS) scores at admission between subgroups in Group 1. However, Injury Severity Score (ISS) values were significantly lower in Subgroups 2 and 3 of Group 2 (p<0.05), likely reflecting improvements in prehospital care and implementation of the “golden hour” principle. All patients underwent continuous hourly hemodynamic monitoring in the intensive care unit. Circadian rhythm parameters of mean arterial pressure (MAP), including mesor, acrophase, bathyphase, amplitude, and daily variability, were calculated to assess temporal hemodynamic patterns and to compare the effectiveness of surgical and conservative management strategies. Patients were transferred to specialized departments upon stabilization of hemodynamics, respiratory function, and neurological status.

3. Results and Discussion

During the first 7 days, statistically significant differences between the groups were identified in the parameters of mesor, acrophase, and bathyphase (Table 1). In Subgroup 2 of Group 2, the mesor level of the circadian rhythm of mean arterial pressure (MAP) was 7% lower than in Group 1, while MAP values in the acrophase were 10% lower and in the bathyphase 11% lower (p<0.05, respectively).

Table 1. Comparative evaluation of the mean values of the circadian rhythm of mean arterial pressure during the first 7 days

In addition, in Subgroup 3 of Group 2, a decrease in the mesor of the circadian rhythm of mean arterial pressure (MAP) by 11% and a reduction in MAP at the bathyphase by 11% were identified (p<0.05, respectively). The observed differences indicate a more effective stress-limiting therapy in Subgroups 2 and 3 of Group 2 during the first 7 days of severe combined traumatic brain injury (SCTBI).

Table 2. Comparative evaluation of mean circadian MAP values during ICU stay

A statistically significant decrease in the mesor of the circadian rhythm of mean arterial pressure (MAP) by 6% and a reduction in MAP at the bathyphase by 10% were identified in Group 2. Signs of less effective intensive stress-limiting therapy were observed in the most severe patients of Subgroup 3 in Group 2, where daily fluctuations of MAP increased by 163% (p<0.05). Thus, despite the achieved effectiveness of comprehensive intensive therapy during the first 7 days in Subgroup 3, excessive daily MAP variability during prolonged intensive care (up to 30 days) indicated insufficient treatment efficacy in these patients (Table 2). In contrast, Subgroup 2 of Group 2 demonstrated a pronounced positive dynamic trend.

Table 3. Dynamics of the mesor of the circadian rhythm of mean arterial pressure (MAP)

No deviations from normal values of the mesor of the circadian rhythm of mean arterial pressure (MAP) were identified on the first day. During follow-up monitoring, a tendency toward an increase in mesor was observed in Group 1, Subgroup 1 on days 19, 22, and 23 by 11%. In Group 2, Subgroup 1, an increase of 19% was noted on day 22. Thus, during ICU observation, no significant intergroup differences were detected in this subgroup. In Group 1, Subgroup 2, an increase in mesor by 12% was observed on days 19 and 20. In contrast, in patients who underwent extracranial surgical procedures (Group 2), no such tendency toward mesor elevation was observed throughout the monitoring period compared with Group 1. Therefore, after day 18, a marked tendency toward an increase in MAP mesor exceeding 10% was identified. We associate this finding with the addition of secondary factors negatively affecting intracerebral hemodynamics, one of the leading factors being bacterial flora mutation with the emergence of resistant strains, occurring against a background of prolonged mechanical ventilation and reduced immune resistance in children with severe combined traumatic brain injury. Comparative analysis according to injury severity (between subgroups) revealed that already on the first day, the mesor of the circadian MAP rhythm in Subgroup 3 was significantly higher than in Subgroup 1 by 11% (p<0.05) and by 8% compared with Subgroup 2 (p>0.05).

The identified statistically significant increase in the mesor of the circadian rhythm of mean arterial pressure (MAP) persisted until day 18. In the subsequent days of observation, the difference decreased due to an increase in MAP mesor values in Subgroup 1. It is well known that the primary causes of elevated MAP include ischemia of the injured brain and increased intracranial pressure in the early hours after trauma, leading to reduced capillary blood flow, worsening ischemia, and potentially resulting in irreversible changes.

Notably, during the first 10 days, the mesor of the circadian rhythm of mean arterial pressure (MAP) was on average 10% significantly lower compared with Subgroup 3 of Group 1, indicating more effective stress-limiting comprehensive intensive therapy. However, in the two patients who remained in the ICU, instability with a tendency toward an increase in the studied parameter was observed in the subsequent days. Thus, the most favorable outcomes of comprehensive treatment in children with severe combined traumatic brain injury were observed during the first 10 days, when optimization of therapy may exert the greatest positive effect on cerebral trophism, contribute to the restoration of cognitive and other brain functions, and improve the overall results of intensive care management in pediatric SCTBI.

In Group 1, among non-operated injured children, the amplitude of the circadian rhythm of mean arterial pressure (MAP) was 6 ± 2 mmHg, whereas in Group 2 this parameter was 9 ± 3 mmHg (Figure 1). In Subgroup 2, injured patients of Group 1 demonstrated more pronounced hemodynamic instability on the first day; however, this did not significantly affect the mean MAP amplitude in patients who underwent extracranial surgical procedures, with amplitude values of 6 ± 3 mmHg in Group 1 and 6 ± 2 mmHg in Group 2 (Figure 2). A substantially more pronounced intergroup difference was observed in children who underwent combined cranial and extracranial surgical interventions. In Subgroup 3, the MAP amplitude in Group 1 was 6 ± 2 mmHg, whereas in Group 2 it reached 15 ± 7 mmHg (Figure 3). The increase in circadian MAP amplitude in Subgroup 3 amounted to 150% (p < 0.05).

Figure 1. Amplitude of the Circadian Rhythm of Mean Arterial Pressure (Subgroup 1)

Figure 2. Amplitude of the Circadian Rhythm of Mean Arterial Pressure (Subgroup 2)

Figure 3. Amplitude of the Circadian Rhythm of Mean Arterial Pressure (Subgroup 3)

More pronounced hemodynamic instability was observed in all three subgroups of Group 2. The most marked difference was identified in Subgroup 3, where daily MAP variability was 11 ± 3 mmHg in Group 1 and 29 ± 12 mmHg in Group 2 (Figure 6). A somewhat less pronounced difference was found in Subgroup 1, where the daily range of MAP fluctuations was 11 ± 3 mmHg in Group 1 and 18 ± 5 mmHg in Group 2 (Figure 4). The least pronounced difference was observed in Subgroup 2: daily MAP variability amounted to 11 ± 4 mmHg in Group 1 and 13 ± 4 mmHg in Group 2 (Figure 5). Thus, daily instability of peripheral vascular tone predominated in injured children of Group 2 across all subgroups. These findings may be explained by less intensive sedative and stress-protective therapy, greater injury severity, or better preservation and realization of compensatory cardiovascular adaptation mechanisms under conditions of more severe brain injury in SCTBI. The results corresponded to injury severity and the degree of acute cerebral insufficiency at admission. In Group 1, the Injury Severity Score (ISS) was 33.7 ± 5.8 in Subgroup 1, 40.5 ± 6.5 in Subgroup 2, and 41.3 ± 4.6 in Subgroup 3. In Group 2, ISS values in Subgroups 2 and 3 were significantly lower than in Group 1 by 45% and 27%, respectively (p < 0.05).

Figure 4. Daily Fluctuations of Mean Arterial Pressure in Subgroup 1

Figure 5. Daily Fluctuations of Mean Arterial Pressure in Subgroup 2

Figure 6. Daily Fluctuations of Mean Arterial Pressure in Subgroup 3

Thus, the comparatively more pronounced changes in the amplitude and daily variability of mean arterial pressure (MAP) in Group 2 may be attributed to a more sparing stress-protective correction, which allowed more active involvement of compensatory mechanisms in ongoing adaptive responses of all systems, including the vascular system, during the postoperative period of severe combined traumatic brain injury in children. In all subgroups of Group 1, a strong positive correlation was identified between mean arterial pressure (MAP) and diastolic arterial pressure (DAP), which weakened in Subgroup 1 while maintaining a tendency toward a direct dependence of MAP on DAP. A slight negative correlation trend was observed between DAP and pulse arterial pressure (PAP) in Subgroups 1 and 3 during the first 10 days of treatment. This tendency persisted in Subgroups 1 and 3 during days 11–30 of intensive therapy. In Group 2, a strong positive correlation between MAP and DAP (r = 0.8) was also identified across all subgroups. In Subgroup 3, the relationship between DAP and PAP shifted and demonstrated a positive trend throughout the entire observation period. Additionally, a positive tendency of direct dependence between MAP and PAP was observed in Subgroups 2 and 3 during days 11–30 of ICU treatment. These findings indicate that changes in DAP exert a predominant influence on MAP levels, whereas PAP has a substantially lesser impact in children with severe combined traumatic brain injury.

4. Conclusions

In Group 2, normalization of the mesor of the circadian rhythm of mean arterial pressure (MAP) was observed. The severity of traumatic brain injury significantly influenced the effectiveness of comprehensive treatment of severe combined traumatic brain injury (SCTBI) and indicates the need to optimize therapeutic strategies in children of Subgroup 3. The comparatively more pronounced changes in MAP amplitude and daily variability in Group 2 may be associated with a more sparing stress-protective correction, which allowed greater activation of compensatory mechanisms in ongoing adaptive responses of all systems, including the vascular system, during the postoperative period. In all subgroups of both groups, a strong positive correlation between MAP and diastolic arterial pressure (DAP) was identified, confirming the predominant influence of DAP changes on MAP levels in children with SCTBI.