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ABOUT RISK-FACTORS OF DEVELOPMENT OF SURGICALLY SIGNIFICANT DELAYED TRAUMATIC INTRACRANIAL HEMATOMAS AFTER ASSOCIATED INJURY Semenov A.V., Krylov V.V., Sorokovikov V.A.

Irkutsk State Medical Academy of Postgraduate Education – Branch of Russian Medical Academy of Continuous Professional Education,

Irkutsk City Clinical Hospital No.3, Irkutsk, Russia

Irkutsk Scientific Center of Surgery and Traumatology, Irkutsk, Russia

Evdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia

 

The first documental description of delayed traumatic intracranial bleedings (DTICB) was made by Otto Böllinger, a German pathologist of Munich University, in 1893. He analyzed four cases of deaths after traumatic brain injury (TBI) [1]. José Álvarez-Sabín and coauthors performed more detailed studies of this problem in the era of computer tomography (CT) and found some features of DTICB: 1) DTICB in adult patients with normal brain CT (without bleeding, fractures and vascular abnormalities) within 6 hours after injury are rare (4.6 % of all TBIs); 2) severity of primary TBI does not influence on their development; 3) DTICB dominate in young patients; 4) period without clinical symptoms is 1-15 days after injury; 5) most DTICBs are deep intracerebral bleedings by the type of parenchymous saturation of small or middle size; 6) the clinical course of DTICB is favorable without surgical management; the mortality is null, without recidivation [2]. The causes of development of such type of DTICB are unclear. Possibly, it is a secondary cerebral injury at the background of a local disorder after TBI [3]. This theory lies in the basis of more frequent increase in the volume of primary foci of cerebral contusion with common formation of surgically significant mainly intracerebral, hematomas (Fig. 1). 

Figure 1

The brain CT-scans of the patient P. Delayed intracerebral hemorrhage: a) CT immediately after hospitalization; b) CT 8 days later at background of conservative treatment.

 

Figure 1a The brain CT-scans of the patient P. Delayed intracerebral hemorrhage: CT immediately after hospitalization	Figure 1b The brain CT-scans of the patient P. Delayed intracerebral hemorrhage: CT 8 days later at background of conservative treatment.

     

One may state that delayed bleedings are more severe in primary cerebral injury with intracranial bleeding in the first hours after the injury.

Another variant of late intracranial bleeding after TBI is delayed traumatic intracranial hematomas (DTICH), including meningeal ones, which sometimes require for surgical treatment. The nature of their development is thrombus detachment or erosion of primarily injured vessel in TBI, especially at the background of dehydratation [4]. Actually, a secondary cerebral injury happens by means of delayed formation of hematoma, compression and dislocation of the brain. Therefore, we deal with the multifactorial (at the morphological level) disease, but with the single pathogenetic mechanism (Fig. 2).

Figure 2

Importance of the secondary brain injury for both delayed hemorrhage (parenchymal saturation) and delayed hematoma.

 

Practically, DTICH is better to consider as one of the variants of DTICB. Considering the relatively rare development in patients with TBI, there is an important issue on influence of external factors such as premorbid anticoagulant therapy and DIC in traumatic hemorrhagic shock. A study by C.E. Albers et al. included 3,088 patients with mild TBI. They did not find any influence of premorbid intake of anticoagulants on intracranial bleedings, considering the gender and age of injured persons [5]. Such results were received in studies by D.K. Nishijima at el. [6] and V.G. Menditto et al. [7]. They found that warfarin and clopidogrel did not influence on development of DTICB before TBI.

The changes in hemostasis in traumatic and hemorrhagic shock have been well studied and present a wave-shaped cascade of responses of clotting and anticlotting systems of the body with alternate dominance [8]. Acute thrombocytopenia at early stages of DIC and its possible influence on DTICB and DTICH in severe TBI are interesting (Fig. 3).

Figure 3

The simplified design of the hemostasis changes as a result of DIC-syndrome in severe associated injury [8].

Objective – to identify possible risk factors of development of surgically significant DTICH in associated injury.

 

MATERIALS AND METHODS

A retrospective comparative analysis of diagnostics and treatment of 30 patients with associated and isolated traumatic brain injury was conducted on the basis of Irkutsk City Clinical Hospital No.3 in 2012-2017. The study corresponded to the ethical standards of Helsinki Declare – Ethical Principles for Medical Research with Human Subjects, and to the Order of Health Ministry of RF No.266, 19 June 2003. Due to the fact that the study was retrospective and did not require for publication of personal data, the written consent was not required.

The inclusion criteria were: 1) correspondence of diagnosis to the Russian classification of injuries [9]; 2) reliable information on presence of traumatic brain injury; 3) absence of surgically significant intracranial hematoma in MSCT in the first 6 hours after the injury; 4) absence of concurrent abnormality of cerebral vessels; 5) for the group of patients with DTICH – presence of a surgically significant intracranial hematoma during recurrent MSCT at least 6 hours after the first examination. The exclusion criteria: 1) childhood; 2) presence of a surgically significant intracranial hematoma at admission.  

Three groups of patients were retrospectively collected: the group A – 8 deceased patients with associated TBI with surgically significant DTICH and correspondence to the selected criteria (meningeal – 7, intracerebral – 1); the group B – 12 patients with associated TBI without DTICH (8 survivals, 4 deceased); the group C – 10 patients with single TBI with DTICH requiring for surgical treatment. The results of main clinical and laboratory studies were examined in all three groups according to our list (coagulograms were collected for the whole period of hospital stay; totally 1,019 examinations). MSCT was used for measurement of optic nerve sheath diameter (ONSD) with our technique – the indirect sign for measurement of intracranial pressure [10] (Fig. 4).

Figure 4

The brain CT-scans of the patient S. Estimation of optic nerve diameter (OND) on an initial brain CT-scan:  a) mild brain injury, OND = 3.9 mm to the right; b) severe brain injury, OND = 6.8 mm to the right – the sign of high intracranial pressure.

Figure 4a The brain CT-scans of the patient S. Estimation of optic nerve diameter (OND) on an initial brain CT-scan: mild brain injury, OND = 3.9 mm to the right	Figure 4b The brain CT-scans of the patient S. Estimation of optic nerve diameter (OND) on an initial brain CT-scan: severe brain injury, OND = 6.8 mm to the right – the sign of high intracranial pressure.

 

All received digital data was converted into the simple mean arithmetic (M) with the formula: М = Ʃν/n, where v - numeric value of a studied sign, Ʃν – the sum, n – number of observations. Then the mean quadratic deviation (σ) was calculated for each mean value using the formula: σ = V_max – V_min / k, where V_max – the value of the highest variant (a digital value) of a studied sign, V_min – the value of the minimal variant, k – the coefficient from the table calculated by S.I. Ermolaev [11]. The mean quadratic deviation was used for calculation of the error in the mean (m) with the formula: m =  or m = , if n ≤ 30. The error in the mean value of the sign was used for calculation of reliability of differences of the studied signs (Student’s test) in the comparison groups with the formula

  t =  (the table 1).

Table 1

Mean values of main clinical and laboratory signs (declinations from normal values are black typed.

Number of sign at admission; normal values and (or) measurement units are in brackets	Group A ATBI with DTICH (n = 8)			Group B ATBI without DTICH  (n = 12)			Group C ITBI with DTICH (n = 10)
	М1	σ2±	m3±	М	σ±	m ±	М	σ  ±	m ±
1. Age (years)	66.5	13.7	5.17	53.8	21.17	6.38	63.7	17.5	5.84
2. GCS (normal – 15)	10.87	2.5	0.93	13.4	2.454	0.739	11.8	2.59	0.86
3. SAP (100-130 mm Hg)	87.75	24.5	9.28	99.25	30.67	9.248	133.7	29.62	10.47
4. DAP (60-80 mm Hg)	51.9	21.05	7.96	56.3	27.6	8.324	80.5	15.15	5.357
5. Pulse (60-80 per min.)	100.6	18.9	7.14	97.8	19.02	5.73	82.9	15.15	5.36
6. ATBII (normal - +6.0)4	2.31	2.1	0.79	4.17	2.15	0.64	-	-	-
7. ISS (points)	34.75	14.4	5.44	33.8	12.58	3.79	-	-	-
8. Time before first MSCT (hours)	3.75	2.21	0.9	9.4	25.0	8.33	51.25	77.76	25.9
9. Mean OND (normal – 5.1±0.7 mm)5	5.03	0.24	0.167	5.63	0.454	0.203	5.37	0.83	0.37
10. Alcohol in blood at admission (normal – 0-0.35‰)	0.66	0.49	0.18	0.49	0.89	0.27	0.9	1.03	0.51
11. INR (normal – -0.7-1.3)6	1.51	0.9	0.28	1.25	0.54	0.08	1.135	0.15	0.02
12. APTT (normal  – 24-35 sec.)	33.6	8.8	2.78	31.1	11.16	1.88	29.33	8.01	1.37
13. SFC (normal  – 4 mg, %)6	11.73	6.94	2.194	16.19	5.936	0.905	20.11	5.697	0.912
14. PTT (normal – 12-20 sec.)6	21.12	8.771	3.315	16.8	6.326	1.136	16.92	1.5	0.294
15. PTI (normal – 95-105 %)	81.5	9.734	9.734	80.05	18.41	4.46	93.83	13.19	3.976
16. Fibrinogen (normal – 2-4 g/l)6	4.196	2.668	0.805	4.371	1.256	0.191	5.231	0.774	0.127
17. Platelets (normal – 180-320 x 109/l)	134.5	70.91	12.34	190.9	130.8	14.19	187.5	64.21	7.674
18. Hemoglobin (normal – 120-160 x 10 g/l)6	85.28	33.82	5.978	99.48	21.06	2.298	107.4	19.46	2.217
19. Red blood cells (normal – 3.9-6.0 x 109/l)6	2.562	0.889	0.165	3.279	0.683	0.078	3.543	0.602	0.069
20. Fat globulemia (normal – 0 points)7	3.0	0.858	0.429	3.0	0.92	0.277	-	-	-
21. Concurrent pathology (%)8	75.0		16.37	83.3		11.24	60.0		16.3
22. Gender (male/female)	4/4			9/3			7/3

Note: 1 – simple mean arithmetic; 2 – standard deviation; 3 – error of mean; 4 – associated traumatic brain injury index (ATBII) [12], 5 – optical nerve diameter (OND); 6 – values of coagulogram and total blood analysis are for the whole period of hospital stay (totally, 1,019 examinations in 3 groups); 7 – mean degree of fat globulemia for the whole period of hospital stay according to N.V. Kornilov et al., 2000 [13]; 8 – relative value – % of patients in the group with associated pathology (HD, DM, IHD etc.) with calculation of alternative value and mean error of relative value.      

RESULTS AND DISCUSSION

The comparison groups A, B and C were homogenous according to most signs: age, time of conduction of initial MSCT of the brain after trauma, concurrent pathology, alcohol in the blood, pulse and main indices of the coagulogram – INR, PTT, PTI, fibrinogen. The groups A and B did not show any significant differences in the index of associated TBI and ISS; all they had fat globulemia (the table 2).

Table 2

Student’s test for significance of differences in mean values (t > 2 – reliable difference (black typed))

Number and name of sign	Student’s test for significance of differences
	А and B	А and C
1. Age	1.54	0.35
2. GCS	2.142	0.7
3. SAP	0.877	3.28
4. DAP	0.387	2.989
5. Pulse	0.31	1.98
6. IATBI	1.829	-
7. ISS	0.143	-
8. Time before initial MSCT	0.674	1.83
9. OND	2.282	0.837
10. Blood alcohol	0.52	0.44
11. INR	0.91	1.33
12. APTT	0.73	1.387
13. SFC	1.878	3.53
14. PTT	1.22	1.263
15. PTI	0.135	1.173
16. Fibrinogen	0.212	1.27
17. Platelets	2.998	3.646
18. Hemoglobin	2.216	3.467
19. Erythrocytes	3.93	5.485
20. Fat globulemia	0	-
21. Concurrent pathology	0.417	0.64
22. Gender (male/female)	4/4	9/3

The table 3 shows all identified statistically significant differences in the signs with use of the symbols “>” (more), “<” (less) and “=” (equal – for cases with unreliable differences in the signs).

Table 3

Quantitative estimation of differences in signs according to principle «more/less/equal» (explained in the text)

GCS, points	ATBI without DTICH	>	ATBI with DTICH	=	ITBI with DTICH
OND (mm)	ATBI without DTICH	>	ATBI with DTICH	=	ITBI with DTICH
Blood platelets (×109/l)	ATBI without DTICH	>	ATBI with DTICH	<	ITBI with DTICH
Red blood cells (×1012/l)	ATBI without DTICH	>	ATBI with DTICH	<	ITBI with DTICH
Hemoglobin (g/l)	ATBI without DTICH	>	ATBI with DTICH	<	ITBI with DTICH
Plasma SFC (mg/100 ml)	ATBI without DTICH	=	ATBI with DTICH	<	ITBI with DTICH
Arterial pressure (mm Hg)	ATBI without DTICH	=	ATBI with DTICH	<	ITBI with DTICH

Note: ATBI – associated traumatic brain injury, ITBI – isolated TBI, DTICH – delayed traumatic intracranial hematoma, OND – optical nerve diameter during initial brain MSCT.

The presented table shows that two factors are especially interesting with differences in the groups: consciousness level and ONSD. The consciousness level according to GCS in associated TBI without DTICH was reliably higher (> 13 points) than in associated and isolated TBI with DTICH. This fact can testify more severe primary injury to the brain in TBI with formation of surgically significant DTICH in associated and isolated injuries.  

ONSD (mm) in associated TBI without DTICH was reliably higher (> 5.5 mm) than in isolated and associated injuries without DTICH. According to the modern literature, ONSD is the most available and quite accurate marker of ICP change [10]. Small ONSD (< 5.05 mm) can testify the absence of intracranial hypertension in primary MSCT and possibly the presence of intracranial hypotension. Formation of extensive intracerebral bleedings is not rare after removal of traumatic meningeal hematomas; it can be related to harp decrease in ICP during surgery. The issue requires for further investigation with higher number of cases.

Thrombocytopenia (< 180 × 10⁹/l) was found in patients with associated TBI and DTICH, whereas the mean value of platelets was within the normal limits in associated TBI without DTICH. The patients with isolated TBI had no thrombocytopenia, but had DTICH. Also arterial pressure, red blood cells and hemoglobin in the blood were reliably lower in patients with associated TBI with DTICH in comparison with associated TBI without DTICH, but also reliably lower than in patients with isolated TBI with DTICH. Therefore, the influence of thrombocytopenia, anemia and arterial hypotension on DTICH in associated injury was doubtful.

SFC were above the normal value in all three groups, but without significant differences in associated TBI with DTICH and without it. There is an interesting fact of higher SFC (the sign of developing DIC) in isolated TBI with DTICH. It confirms the possibility of initiation of DIC in isolated TBI, possibly due to release of high level of tissue thromboplastin in neuronal tissue [8].   

CONCLUSION

The study showed that the associated injury and traumatic (hemorrhagic) shock do not make a high influence on development of surgically significant DTICH. Patients with associated and isolated TBI have the higher risk of surgically significant DTICH if they demonstrate the following signs at admission: 1) GCS < 12; 2) ONSD < 5.1 m according to results of MSCT (the indirect sign of low ICP).    

The future studies of the influence of normal or low intracranial pressure on development of delayed bleedings with consideration of possible changes in hemostasis, which are common for DIC in both associated and isolated TBI.

Information on financing and conflict of interests

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