SIGNIFICANCE OF CONTROL OF INTRACRANIAL PRESSURE AND REGULATION OF SODIUM IN TRAUMATIC BRAIN INJURY IN CHILDREN Fogel I.A., Shmakov A.N., Budarova K.V., Kokhno V.N., Elizar'eva N.L.

Novosibirsk State Medical University,

Novosibirsk, Russia

Traumatic brain injury can be called as directed pathology only figuratively. Complications and mortality depend on massiveness and location of an injury, closeness of a contusion focus to the hypothalamus, incidence and location of penumbra zone, timeliness and orientation of intensive care from the prehospital stage [1, 2, 3]. In childhood age, traumatic brain injuries proceed more favorably than in adults. It is associated with multiple reasons: elasticity of cranial bones which partially suppresses the impact wave; higher blood flow as compared to adults which reduces events of local ischemia with subsequent reperfusion; high velocity of energetic and substrate metabolism, providing efficient sanogenesis [1, 4].

Nevertheless, the mortality after traumatic brain injury is also high in childhood, reaching 12-30 % according to the data by Semenova Zh.B. [1]. Neurological disability after traumatic brain injury is also high, but is has not been studied well. Particularly, there is scarce evidence of long term consequences of traumatic brain injury [1, 5]. In acute posttraumatic period, the main factors, which determine probability of lethal outcome and (or) disabling neurological complications, are uncontrolled intracranial hypertension [6, 7] and disorder of osmotic balance between blood plasma and brain interstitium, resulting in hypernatremia [8].

However quantitative estimation of significance of these factors is variable in literature. There are some opinions in favor of necessity of intracranial pressure control [6, 9], and, conversely, for low therapeutic value of this method [10]. Moderate hypernatremia in the first 2-4 days after trauma can be the compensatory factor and can provide a decrease in flow of intravascular fluid into brain interstitium [1], but persistent plasma hyperosmolarity can be a cause of persistent severe disorders of dynamics of blood and liquor [12]. Correlation studies, one of which is presented in this article, present an efficient tool for comparative estimation of importance of measurement of sodium level in plasma and for intracranial pressure control.

Objective − to evaluate the diagnostic and therapeutic significance of monitoring of intracranial pressure and plasma sodium concentration for intensive care of children with traumatic brain injury.

MATERIALS AND METHODS

A study was conducted on the basis of the anesthesiology and intensive care unit of surgical profile of Novosibirsk Pediatric City Clinical Hospital No. 1, and was approved by the local ethical committee (the protocol No. 3, 2018).

The initial sample included children at the age from 3 months to 15 years, who were admitted with traumatic brain injury in 2019. Children with birth trauma, with background disabling neurological pathology without need for prolonged artificial lung ventilation (ALV) at least for 24 hours were excluded (9 patients). The general study sample was 40 patients. Glasgow Coma Scale was less than 8 points in all patients at the moment of admission. In the first day, all patients received decompressive trepanation, with removal of hematomas according to indications. The age distribution: the median − 36 months, the variation range − 6-180 months of postnatal life. The gender distribution: 25 boys (63 %), 15 girls (37 %). 8 patients died (20 %).

Intensive care was conducted according to the general strategic plan: Fowler's position with alternated angle of inclination of the bed head; rehydratation volume (all delivery of water) of 1,500 ml/m² per day with maintenance of null or negative daily balance and with variations of cumulative balance for 3 days ± 3 % of the basic body weight; analgesia with fentanyl; sedation with infusion of thiopental natrium; early enteral nutrition; control of hydroionic, acid-base and osmotic balance; respiratory therapy with SIMV with the most efficient targeted parameters: PEEP 4-8 mm Hg, PCO₂ 35-45 mm Hg, Р50 with slight shift to the right (29-32 mm Hg), with switch to spontaneous breathing along with recovery of breathing rhythm, cough and swallow reflexes; control of platelet hemostasis and coagulation activity of blood. Most patients (33 persons, 82 %) required for inotropic and vasopressor support with dopamine (8-11 µg/kg/min); 7 patients required for pressor support with adrenaline (0.2-0.5 µg/kg/min). Osmotic active substances (mannitol) were used for 5 patients (3 patients died, 2 − survived with favorable outcomes). Quantitative correction of the management parameters was conducted under control of intracranial pressure or in empirical manner with no transducer.

The analyzed values: the highest level of sodium ion in plasma (mmol/l); time of natriemia normalization (days); ALV duration (days); outcomes after transfer to specialized units according to Pediatric Cerebral Performance Category Scale (PCPCS) [Fiser D.H., 1992]. The values were analyzed in the comparison groups: the group 1 − 13 patients who received regulation of intensive care parameters under control of ICP monitoring, with consideration of ICP ≤ 20 mm Hg as the targeted value; the group 2 − 27 patients without ICP transducer, and intensive care parameters were managed empirically. Some positions were analyzed separately for deceased (8 patients) and survived (32 patients).

The statistical analysis of results was conducted with non-parametrical statistical methods since data distribution did not follow the normal distribution law (Shapir-Wilx test). Mann-Whitney's test was used for intergroup comparisons. χ²-test and Fisher's exact test were used for comparison of discrete values. Rank correlation analysis was conducted according to Spearman's method with determination of correlation coefficients (r) and proportion of direct coincidences (R²). The results were presented as the median [lower quartile; upper quartile] (Me [Q25; Q75]). ROC-analysis was presented by calculation of area under ROC, 95 % CI, sensitivity (Se) and specificity (Sp). The null hypothesis was rejected at p < 0.05.

RESULTS AND DISCUSSION

The table 1 shows the results of the study. As one can see, the incidence of hypernatremia was high in all patients regardless of an outcome (p = 0.655; Fisher's exact test). Moreover, more intense hypernatremia was associated with a lethal outcome as compared to patients with favorable outcome. Age and gender did not influence on the mortality. 2 kids at the age < 1 year were in the group of patients with lethal outcomes, in the survival group − 6 (p = 0.650; Fisher's exact test). Generally, the age data were comparable according to groups (p = 0.170; Mann-Whitney's test). There were 5 boys (63 %) and 3 girls (37 %) among deceased. It corresponds to general gender distribution as a whole.

Table 1

Age and analyzed parameters in patient samples: median (Me); lower and upper quartiles [Q25; Q75]

Indicators	Samples from the general population (N = 40)	Values Ме [Q25; Q75]
Age (months)	Dead (N = 8)	24 [8; 110]
Age (months)	Survivors (N = 32)	38 [9; 122]
Number of patients with hypernatremia	Dead (N = 8)	7 (88 %)
Number of patients with hypernatremia	Survivors (N = 32)	24 (75%)
Plasma Sodium (mmol/L)	Dead (N = 8)	161 [152; 166]
Plasma Sodium (mmol/L)	Survivors (N = 32)	149 [142; 154]*
Normalization time of natriemia (days)	Survivors with hypernatremia (N = 24)	4 [2; 6]
Time on mechanical ventilation (days)	Survivors (N = 32)	3 [1; 8]
Outcome at the time of transfer: Pediatric Cerebral Performance Category Scale (PCPCS) points	Survivors (N = 32)	2 [2; 3]
Maximum value of intracranial pressure (mm Hg)	Part of general population (N = 13)	24 [12; 30]

Note: * – a significant difference from the value of the indicator in the dead: T = 231.0; p = 0.024; Mann-Whitney test)

The table 2 shows the results in the group of ICP monitoring and in the group without estimation of this value.

Table 2

The studied parameters in survived patients, depending on the presence of intracranial pressure control: median (Me); lower and upper quartiles [Q25; Q75]

Indicators	ICP monitoring (N = 11)	Absence ICP monitoring (N = 21)
Plasma Sodium (mmol/L)	151 [148; 155]	148 [142; 158]
Normalization time of natriemia (days)	3 [2; 5]	5 [2; 9]
Time on mechanical ventilation (days)	3 [2; 8]	3 [2; 9]
2 points for Pediatric Cerebral Performance Category Scale (PCPCS)	7 (64 %)	11 (52 %)
3 points for Pediatric Cerebral Performance Category Scale (PCPCS)	4 (36 %)	10 (48 %)
Died (absolute number, %)	2 (15 %)	6 (22 %)

During estimation of outcomes of neurological situations, PCPCS of 2 points corresponded to good recovery of functions, 3 points − satisfactory. Visually, patients with ICP monitoring demonstrated some better values of life quality and survival (faster normalization of natriemia and adequate spontaneous breathing; better recovery of cerebral functions by the moment of transfer to a profile unit; lower mortality), but without statistical differences.

The table 3 shows the results of rank correlation analysis. The analysis included only survived patients since normalization of natriemia is basically unachievable in the subgroup with lethal outcomes.

Table 3

Correlations of the studied parameters in survived patients

Compared pairs	Количество и характеристики пар Number and characteristics of pairs (N)	r	R²	p
Natriemia / Time on mechanical ventilation	N = 32 (all)	0.707	0.5	0.000
Natriemia / Outcome (PCPCS)	N = 32 (all)	0.651	0.42	0.000
Normalization time of natriemia / Time on mechanical ventilation	N = 32 (all)	0.793	0.63	0.000
Normalization time of natriemia / Outcome (PCPCS)	N = 32 (all)	0.779	0.61	0.000
Normalization time of natriemia / Natriemia	N = 14 (with initial hypernatremia without ICP control)	0.680	0.46	0.000
Normalization time of natriemia / Natriemia	N = 10 (with initial hypernatremia with ICP control )	0.609	0.37	0.048
Intracranial pressure / Outcome (PCPCS)	N = 11 (with ICP monitoring)	0.683	0.47	0.012
Intracranial pressure / Time on mechanical ventilation	N = 11 (with ICP monitoring)	0.705	0.5	0.019
Intracranial pressure / Normalization time of natriemia	N = 11 (with ICP monitoring)	0.348	0.12	0.286
Intracranial pressure / Natriemia	N = 11 (with ICP monitoring)	0.240	0.06	0.415

The comparison of R₂ values, which characterize the proportion of true proportional coincidences of the compared signs, showed that the time of natriemia normalization was more associated with ALV duration and quality of outcome of acute phase of TBI as compared to degree of hypernatremia. Correlation of hypernatremia degree with its duration was average. Moreover, the coefficient decreased significantly in patients with controlled ICP. A decrease in correlation strength reflects the therapeutic value of ICP control, i.e. possibility for ICP regulation with analgetic sedation without active natriuresis. The mean direct correlations between maximal measured ICP and an outcome of acute period of TBI (ALV duration, estimation of cerebral functions) are quite predictable and do not require for comments. Practical absence of direct correlations between maximal levels of ICP and hypernatremia testifies an independent significance of these signs for prediction of treatment outcomes. Actually, it is known that ICP responses quickly and actively to changes in cerebral blood flow, and with lesser degree − to incoordination of osmolarity of liquor and plasma, and it weakly responses to change in liquor production [12, 13].

The predictive ability of time of normalization of sodium level was confirmed by ROC-analysis. AUC = 0.885 ± 0.07, p < 0.001, 95 % CI (0.688; 0.978). Active control of ICP stopped an increase in sodium on the second day (Se 27.27 %, Sp 100 %) (Fig. 1).

Figure 1

ROC-curve of time of normalization of plasma sodium concentration in children (N = 30)

Figure 1 ROC-curve of time of normalization of plasma sodium concentration in children (N = 30)

The lower significance was demonstrated by a study of maximal level of sodium (Fig. 2): AUC = 0.845 ± 0.09, p < 0.001, 95 % CI (0.655; 0.955). The predictive bordering was shown by the cut-off point of sodium level > 156 mmol/l (Se 83.33 %, Sp 76.19 %). Therefore, the value of peak hypernatremia is the critical criterion of an unfavorable outcome.

Figure 2

ROC curve of maximum plasma sodium concentration in children (N = 30)

Figure 2 ROC curve of maximum plasma sodium concentration in children (N = 30)

CONCLUSION

1. The age do not determine the prognosis of the course of traumatic brain injury in children.

2. Hypernatremia is a typical sign of traumatic brain injury in children.

3. Both a degree of hypernatremia and its duration are the values of severity of posttraumatic process and markers of its outcome.

4. Intracranial pressure control increases the manageability of this value and prognosis of traumatic brain injury, but possibilities of ICP monitoring are difficult to estimate properly in conditions of posttraumatic intracranial inflammation, undergone pain and (or) hemorrhagic shock and other factors of severe trauma.

Information on financing and conflict of interests

The study was conducted without sponsorship. The authors declare the absence of any clear and potential conflicts of interests relating to publication of this article.