Effects of decompressive craniectomy combined with edaravone on postoperative neurological functions and hemodynamics of patients with severe traumatic brain injury

Subjects

The ethics committee of the hospital issued an approval for the present study, which was performed in accordance with the Helsinki Declaration principles. Strictly based on the ethical standards of the hospital, the subjects and their family members provided the consent form after being informed of the study. The subjects were selected from STBI patients (186 in total) who were hospitalized during January 2018 and January 2021. The random number table method was utilized to establish an operation group (n=82) together with a combined medication group (n=104) for the subjects. To be specific, the subjects were numbered one by one from 001 to 104. The starting point and order of sampling in the random number table were arbitrarily determined. Then all the numbers were selected by the subjects from the table in turn.

The operation group consisted of 43 females plus 39 males aged (52.69±5.92) years old on average. The duration from the injury to admission was 9 hours and (1.68±0.19) hours on average. The injuries included blow injury (9 cases), fall injury (20 cases), traffic accident injury (36 cases) and others (17 cases). The combined medication group had 53 males and 51 females aged (52.73±5.88) years old averagely. The duration from the injury to admission was 0.3-1.8 hours and the mean duration was (1.64±0.23) hour. The causes of injury included blow injury (11 cases), fall injury (25 cases), traffic accident injury (41 cases), and others (27 cases). The above data were comparable between the 2 groups (p>0.05).

The following inclusion criteria were adopted: 1) Patients diagnosed with STBI based on the Modern Craniocerebral Injury and confirmed by CT and MRI, 2) those undergoing an operation at 24 h after admission, and 3) those without multiple or recurrent injuries.

The exclusion criteria involved 1) patients suffering chest, abdominal, or limb trauma, 2) those complicated with severe central nervous system disease, cerebrovascular disease or systemic infections, or 3) those with vascular stenosis or spasm.

Treatment methods

Both groups were subjected to hemostasis, anti-inflammation, dehydration and nutritional support medications after admission. The operation group received craniectomy under stepwise decompression as follows. The whole scalp was first cut by making incisions at the frontal, temporal and parietal lobes, and hemostasis was performed in time. The periosteum was then peeled and the skin flap was separated. After bone drilling and sawing, the bone flap was removed, and the medial and lateral sphenoid ridge was taken out with a bone cutter, followed by decompression. Afterwards, the patients were given intravenously 40-80 mg of furosemide and 250 mL of 20% mannitol. The cerebrospinal fluid and intracranial hematoma were released in a controlled manner through a small hole in the blue dura. After the bone window pressure was released, a radial incision was made on the dura to fully remove the deactivated cerebral tissues and intracranial hematoma. In the case of insignificant or weak brain tissue pulsatility, it is necessary to reduce the brain herniation, with corresponding treatment depending on the particular situations.

The combined medication group was treated with craniectomy under stepwise decompression combined with edaravone (Nanjing Simcere Dongyuan Pharmaceutics Co., Ltd., Nanjing, China; 20 mL: 30 mg). The mixture of edaravone and 0.9% NaCl solution (30 mg evenly diluted in 100 mL) was infused intravenously within 30 min twice a day for 2 weeks. The treatment outcomes were observed after treatment.

Determination of neurobehavioral cognitive status examination (NCSE) score and Barthel index score. The NCSE was used to assess the cognitive status, and the score was in direct proportion to the cognitive status of the subjects. The subjects were also evaluated on the activities of daily living from 10 aspects, including eating, bathing, dressing, walking on a level ground, going up and down stairs, and controlling urination and defecation with Barthel index. The total score was 100 points, and the score was directly proportional to the activities of daily living.

Detection of hemodynamics indicators

The number of pulse beats per min was measured by feeling the pulse when the subjects were in a calm state. The mean arterial pressure (MAP) was determined using direct manometry. A special catheter was percutaneously punctured and the arteries around the catheter were inserted into the aorta and connected to a monitoring manometer at the end of the catheter, and the blood pressure was recorded after being displayed. The ipsilateral and contralateral blood flow velocities in the middle cerebral artery were measured by Voluson E8 TruScanTM color Doppler flow imager (Shanghai Hanfei Medical Devices Co., Ltd., Shanghai, China). Transcranial Doppler ultrasound examination was conducted on all the subjects in a quiet state without abnormal conditions before and after treatment. A 2 MHz probe was placed in the temporal windows above the zygomatic arch and between the orbit and the ear, and the middle cerebral artery was selected as the target vessel with a detection depth of 40-65 mm.

Detection of myocardial zymogram indicators

The levels of aspartate aminotransferase (AST; 10-40 U/L as the reference value), creatine kinase (CK; reference value at 50-310 U/L and 40-200 U/L for male and female, respectively), as well as CK-MB (reference value: 0-25 U/L) were detected by a Libang i15 blood gas automatic biochemical analyzer (Shanghai Hanfei Medical Devices Co., Ltd., Shanghai, China) strictly according to the instructions.

Examination of postoperative neurological functions

Each subject underwent collection of fasting venous blood (5 mL) at 9:00 am before and after treatment. The supernatant was obtained by centrifuging the samples (radius: 15 cm, speed: 3,000 r/min, time: 10 min), followed by preservation using a refrigerator (-80°C) for subsequent assays. Enzyme-linked immunosorbent assay was conducted to determine ES (reference value: 12.7-38.4 pg/ml), neuropeptide Y (NPY; reference value: 101-189.2 pg/ml) and endothelin-1 (ET-1; reference value: 43.22-58.38 pg/ml). The serum samples were first taken out from the refrigerator and stored at room temperature for 30 seconds, and standard serum and solution were prepared. The plate was washed using 300 µL of plate-washing solution for 30 seconds. After the micro-wells were patted dry, the plate was added successively with 50 µL of buffer, standard solution, sample and detection antibody, sealed, shaken and incubated for 2 h at room temperature (37°C). Then the plate wells were added with enzyme marker (100 µL) after washing. The plate was also sealed, shaken and placed at room temperature for 45 min. Following plate washing, the micro-wells were added with substrate solution in a volume of 100 µL for 30 min of incubation in dark. Subsequently, the micro-wells were added with 100 µL of stop buffer and shaken. Finally, a microplate reader was employed to examine at 450 nm for the absorbance.

Evaluation of treatment outcomes

The treatment outcomes (marked response, moderate response and no response) were evaluated based on the NCSE score and Barthel index score. The degree of improvement ≥21 points was marked response, the degree of improvement of 8-20 points represented moderate response, and those failing to meet the above criteria indicated no response. Total response rate=marked response rate+moderate response rate.

Observation of complications

The incidence rates of intraoperative and postoperative complications of patients, including acute intraoperative encephalocele, delayed intracranial hematoma, severe hyponatremia, and large-area cerebral infarction were compared between the 2 groups.

Observation of postoperative 1-year prognosis

The prognosis of the patients was followed up and recorded according to the criteria of death, vegetative survival, severe disability, moderate disability, and good recovery at 1 year after operation.

Statistical analysis

Statistical analysis was performed by means of SPSS 26.0 software provided by IBM Inc. (Armonk, New York, NY, USA). The format of () was utilized to express measurement data. The comparisons between and within groups were accomplished through independent-samples t-test and paired t-test, respectively. The percentage (%) was selected for presenting count data. A p<0.05 indicated a statistically significant difference.