A Clinical Study on Hyperbaric Oxygen Therapy to Treat Severe Traumatic Brain Injury Traumatic Brain Injury

DOI: https://doi.org/10.21203/rs.3.rs-27264/v1

Abstract

This clinical research initiates to study the early hyperbaric oxygen therapy applied in Severe Traumatic Brain Injury based on lots of clinical treatment practice for the Severe Craniocerebral Injury patients, whose survival and rehabilitation has drawn great attention among neurosurgeon experts.

Background: 1. To investigate the clinical effect of early stage hyperbaric oxygen therapy in the treatment of severe traumatic brain injury; 2. To study the treatment therapy of when to apply hyperbaric oxygen therapy to Severe Craniocerebral Injury patients; 3. To study if combining removal of intracerebral hematoma and craniotomy decompression with early stage hyperbaric oxygen therapy can achieve more effective treatment results.

Methodology: 90 cases of severe craniocerebral injury patients admitted to neurosurgery department of 3201 hospital affiliated of Xi’an Jiaotong university were randomly divided into observation group and control group from January 2016 to January 2017, craniotomy for decompression and removal of intracerebral hematoma were performed in both groups. Hyperbaric oxygen therapy was started in the early postoperative period in the observation group and in the late postoperative period in the control group. The Glasgow Coma Scale Score (GCS) of the two groups were compared before and after operation. Patients were followed up for 6 months, the clinical prognosis was assessed by the Glasgow Outcome Scale Score (GOS) and long-term Karnofsky Performance Status Score (KPS).

Results: After treatment, GCS (Glasgow Coma Scale Score) scores of observation group was significantly higher than that of control group (P<O.05); After 6 months’ follow-up, the GOS (Glasgow Outcome Scale score) scores of observation group was significantly higher than that of control group (P<0.05), the favorable prognosis rate was significantly higher than that of the control group (P<0.05). The KPS (Karnofsky Performance Status Score) scores of the observation group were significantly better than that of the control group, and the difference was statistically significant (P < 0.05).

Conclusion: Combing craniotomy decompression and removal of intracerebral hematoma with early hyperbaric oxygen-assisted therapy can significantly improve the survival rate, recovery rate and clinical prognosis of patients with severe traumatic brain injury.

1. Background

 Severe traumatic brain injury (STBI) is a traumatic brain disease caused by the direct or indirect effect of violence on the head, resulting in brain tissue damage accompanied by coma and the Glasgow coma scale score (GCS)≤8 points[1]. STBI (Severe traumatic brain injury) has a high disability rate and mortality rate. At present, most of the neurosurgeons advocate emergency craniotomy for decompression to relieve intracranial mechanical compression and reduce intracranial hypertension, among which the SLTC (standard large trauma craniotomy), the therapy of standard decompression of large traumatic bone flap, has been accepted by doctors at home and abroad[2]. Since standard large trauma craniotomy (SLTC) cannot control secondary brain injury after STBI, it is necessary to cooperate with multi-form and multi-channel comprehensive intervention after surgery to improve the hypoxia of tissues and promote the recovery of nerve function[3]. Hyperbaric oxygen is an important auxiliary means for clinical treatment of STBI, and it has been proved by many basic studies and clinical practices to have good effects in promoting postoperative rehabilitation, but the specific timing of intervention and its effect on prognosis have not been determined yet [4]. This study compared the effects of early and late hyperbaric oxygen assisted SLTC in the treatment of STBI to explore which treatment method is more effective.

2. Material And Methods

2.1 data sources

90 cases of STBI patients admitted to 3201 hospital from January 2016 to January 2017 were selected, all of whom were confirmed by head CT or MRI examination. Patients were divided into observation group and control group according to the random number table method, with 45 cases in each group. In the observation group, there were 26 males and 19 females, aged 25-59 years, with an average (45.32±5.12); Causes of injuries: 23 cases of car accidents, 15 cases of fall injuries, 7 cases of blow injuries; The average time from injury to surgery was 3 ~ 24 h with an average (11.21±1.23) h; Injury types: 24 cases of epidural hematoma, 17 cases of cerebral contusion with subdural hematoma, 4 cases of diffuse cerebral swelling; The hematoma volume was 28~100 ml, with an average (39.82±3.31) ml. Coma status: 32 cases remained in coma after injury, and 13 cases remained in coma after sober. Dilated pupil: 28 cases unilateral, 17 cases bilateral. In the control group, there were 24 males and 21 females, aged 27 ~ 60 years, with an average (43.19±4.79);Causes of injuries: 22 cases of car accidents, 14 cases of fall injuries, 9 cases of blow injuries; The average time from injury to surgery was 4 ~ 24 h (9.55±1.41) h; Injury types: 21 cases of epidural hematoma, 22 cases of cerebral contusion with subdural hematoma, 2 cases of diffuse cerebral swelling; The hematoma volume was 25 ~ 100 ml, with an average (38.05±3.46) ml. Coma status: 30 patients remained in coma after injury, and 15 patients were in coma again after sober. Dilated pupil: 31 cases unilateral, 14 cases bilateral. There was no statistically significant difference in age, sex and cause of injury between the two groups (P > 0.05).

2.2 Inclusion and exclusion criteria

To secure the effectivity of the experiment, the STBI case patients who are chosen for this research has been strictly screened by the inclusion criteria and exclusion criteria.

2.2.1 Inclusion criteria : (1) a clear history of trauma and admission within 24 h after injury; (2) The patients must meet the indications of emergency SLTC surgery; (3) GCS (Glasgow Coma Scale) score is 3-8 and lasts for more than 12 hours; (4) the patient's family members gave informed consent to the research content and signed the informed consent.

2.2.2 exclusion criteria :(1) Complicated with dysfunction of heart, liver, kidney and other important organs;(2) patients with coagulation dysfunction, brain tumor, and other diseases;(3) patients with hypotensive shock, cerebral edema, cerebral ischemia, intracranial infection and other diseases difficult to correct before operation;(4) pulmonary bullae and tympanic membrane perforation; (5) patients with delayed intracranial hematoma after operation who need to undergo secondary craniotomy.

2.3 treatment

After admission to the 3201 hospital, both groups were given immediate support treatment and vital signs monitoring, including hemostasis, dehydration, intracranial pressure reduction, anti-inflammatory, neurotrophic drug, tracheotomy, adjustment of acid-base and water-electrolyte balance. And SLTC was implemented by the same group of anesthesia and surgeon. After the operation, hyperbaric oxygen assisted therapy was performed by the same group of doctors.

2.3.1 Surgical Method: Methods of SLTC surgery: disinfection, anesthesia, and expansion or reduction of bone window as appropriate. An incision was made at the site 1.0cm in front of the zygomatic arch, extending to the front of the parietal tuberosity through the upper and posterior auricle, and extending to the site 2.0cm away from the median sagittal line, and then extending the incision forward to the patient's forehead hairline parallel to the median line, paying attention to protect the superficial temporal artery and the temporal branch of the facial nerve throughout. Free temporal muscle flap of scalp together or separately. The bone flap was flattened the upper zygomatic arch margin downward, was flattened the skin margin forward, and is 2.0cm away from the midline. The rest of the bone flap is attached to the skin margin to open the bone window; the bone window range is about 2/3 of the total cranial area above the curtain.  Removal of hematoma: the epidural hematoma was removed, and the hematoma in the middle meningeal artery and sphenoid crest was carefully treated to prevent delayed hematoma after surgery. The dura was radial cut, open to fully expose the lateral fissure and surrounding tissue. The subdural hematoma and intracerebral hematoma were fully removed, and the contusion and necrotic brain tissue were removed as well. Suture dura: the artificial dura was selected to expand and reduce the tension of the dura, and the temporal muscle was reduced and sutured to prevent or reduce postoperative intracranial hypertension and cerebral edema. A drainage tube was placed subcutaneously or subdural. Intraoperative tracheotomy was implemented to ensure airway patency and pulmonary inflammation easy to control.

2.3.2 Hyperbaric Oxygen Treatment Method: The observation group received Hyperbaric Oxygen treatment at 4 ~ 8 days after the injury while the control group received Hyperbaric Oxygen treatment at 15-30 days after the injury. Air pressurized oxygen chamber was used for treatment with pressure of 0.22-0.23 kPa, oxygen concentration<23%, pressure time 15-20 min, stable oxygen intake 60 min, rest 10 min, slow decompression, decompression time 20-25 min. Once a day, 10 times is a course of treatment. At the end of every course of treatment, the patients had a rest for 3 days. And all the patients received 3 consecutive courses of treatment.

2.4. Observational indicators

(1) After 3 courses of treatment with hyperbaric oxygen treatment, the coma degree of the patients was evaluated by GCS (Glasgow Coma Scale Score), including eye opening reaction, language reaction and body movement. The total score was 0-15, ≤8 was coma, 9-11 was classified as moderate consciousness disorder, 12-14 was classified as mild consciousness disorder, and 15 was normal.

2.5 efficacy criteria

The Glasgow Outcome Scale score (GOS) was used to evaluate the clinical prognosis after 6 months of follow-up. The GOS was divided into 5 scales, 5 grades for good recovery, 4 grades for mild disability, 3 grades for moderate disability, 2 grades for plant survival and 1 grade for death. The KPS (Karnofsky Performance Status Score) score was judged based on the long-term card functional status rating scale, with a total score of 100, and the higher the score, the better the recovery of patients.

2.6 statistical methods

SPSS19.0 statistical software was used for data analysis. Measurement data were expressed as mean ± standard error (x±s) and t-test was adopted. Counting data were expressed as rate (%), chi-square test was adopted, rank sum test was adopted for grade data, and P<0.05 was considered significant difference.

3. Results

GCS (Glasgow Coma Scale Score) scores before and after hyperbaric oxygen treatment were compared between the two groups. There was no statistically significant difference in GCS scores between the two groups before treatment (P>0.05), which was significantly improved after treatment, and the observation group was significantly higher than the control group (P<0.05). (Table1)

Table 1
Comparison of GCS scores between the two groups before and after treatment
Group
Sample
Before treatment
After treatment
T value
P
Observation
45
6.45 ± 1.12
12.96 ± 2.46
14.678
0.000
Control
45
6.56 ± 1.15
10.15 ± 2.20
9.248
0.000
T value
 
0.352
5.631
   
P
 
0.748
0.000
   

After 6 months of follow-up, the GOS (Glasgow Outcome Scale score) scores of the observation group was (5.09±0.46), significantly higher than that of the control group (3.28±0.34) (2=10.427, p=0.000). The favorable prognosis rate in the observation group was significantly higher than that in the control group (P<0.05) (Table2)


Table 2
Comparison of GOS scores between the two groups after treatment (n, %)
Group
Sample
Recover well
Mild disability
Severe disability
vegetative
Death
Favorable prognosis
Observation
45
6(13.33)
31(68.89)
7(15.56)
0(0.00)
1(2.22)
37(82.22)
Control
45
2(4.44)
20(44.44)
17(37.78)
2(4.44)
4(8.89)
22(44.90)
χ2
10.518
9.647
P
10.518
0.002

After 6 months of treatment, KPS (Karnofsky Performance Status Score) scores of the observation group was significantly higher than that of the control group, and the difference was statistically significant. Compared with the observation group, t = 7.351, P = 0.000. The proportion of KPS ≥ 50 in the observation group was also significantly higher than that in the control group, with statistically significant difference, chi-square = 4.028, P = 0.045. (Table 3)

Table 3
Comparison of KPS scores after 6 months of treatment (n, %)
Group
Sample
≥ 50 score
༜50 score
Average
Observation
45
32 (71.119)
13 (28.89)
78.13 ± 14.5
Control
45
26 (57.78)
19 (42.22)
64.8 ± 11.2

4. Discussion

STBI (severe traumatic brain injury) is characterized by acute illness, severe illness, rapid development and change, and high mortality rate, especially for patients with severe intracranial hematoma, cerebral edema, cerebral contusion and laceration, who need emergency craniotomy[5]. SLTC neurosurgery is currently recognized as the most effective way to early treatment for STBI[6]. It can effectively remove intracranial hematoma and brain contusion necrosis, sufficiently reduce intracranial pressure, benefit brain tissue restoration, quickly alleviate or eliminate the physical factors which directly or indirectly lead to brain damage, create favorable conditions for subsequent comprehensive treatment, and win the precious time[7]. However, secondary brain injury caused by various direct or indirect factors after STBI is difficult to be controlled by SLTC (standard large trauma craniotomy), and such secondary brain injury is the main cause of disability or death of STBI patients[8]. The STBI mechanism of secondary brain injury is relatively complex, mainly including oxidative damage, inflammation, toxicity of excitatory amino acids, etc. These factors can work together and cause brain cell injury and apoptosis, blood-brain barrier damage, resulting in brain edema and brain swelling, intracranial pressure and cerebral vasospasm, which further aggravate the brain tissue hypoxia ischemic injury and brain cell metabolism disorder[9]. A vicious cycle of cerebral edema - hypoxia - edema is easily formed, leading to poor prognosis of patients[10]. Therefore, in addition to SLTC surgery, STBI patients should also be treated with effective hyperbaric oxygen therapy to inhibit the secondary pathophysiological changes after STBI and promote the recovery of neurological function[11]. Animal studies (experiment of rabbit brain injury) have shown that hyperbaric oxygen therapy can promote the expression of bcl-2 and inhibit the expression of Bax, thereby inhibiting the apoptosis of brain cells after brain injury[12]. Other studies have shown that hyperbaric oxygen therapy can effectively block the large amount of oxygen free radicals generated by hypoxia, inhibit the formation of lipid peroxidation and its products, and maintain the structure and function of neurons [13].

In this study, the research proved that HBO (hyperbaric oxygen therapy) adjuvant therapy in the early stage for STBI can effectively improve the survival rate of patients, promote the recovery of consciousness, and facilitate the prognosis of GOS. This research also showed that after combining HBO with SLTC, the GCS score of STBI patients were significantly higher than those without HBO (hyperbaric oxygen therapy) treatment. During the process of observation, it was also discovered that early HBO treatment after injury can shorten the awaking time and hospitalization time of STBI patients, and the clinical prognosis rate was significantly improved. The experiment data in this clinical research has demonstrated that the GCS score, the GOS score and the KPS score of STBI patients who received SLTC treatment combined with HBO in the early stage were significantly improved. Compared with the control group, the GCS score of the observation group receiving HBO treatment after injury was significantly higher than that of the control group (P<0).05). After 6 months of follow-up, the average GOS score of the observation group was significantly higher than that of the control group, and the overall prognosis rate was significantly higher than that of the control group. The KPS score of the observation group was significantly higher than that of the control group, and the proportion of patients with KPS≥50 in the observation group was also significantly higher than that of the control group. All the data showed that early HBO treatment after severe brain injury can effectively break the vicious cycle of secondary brain injury, recover the brain nerve function more quickly, and improve the clinical prognosis greatly in the case of excluding HBO contraindication. The main reason is that the secondary brain injury after STBI is progressive and it changes rapidly. If it’s not treated in time, it may develop into unrecoverable brain function damage and even endanger the life of patients. Early intervention of HBO under the condition of basically stable condition can quickly and effectively protect the brain nerve function, promote the remodeling of brain tissue function, and improve the clinical prognosis.

In this research, the efficacy of hyperbaric oxygen therapy on severe craniocerebral injury was studied and the GCS, GOS and KPS system was applied to score. The results showed that hyperbaric oxygen therapy was of great significance in improving the neurological function of patients and reducing sequelae in the clinical treatment of severe craniocerebral injury. It is a very effective clinical treatment. Early hyperbaric oxygen therapy on the basis of conventional treatment can significantly shorten the course of treatment for patients with severe craniocerebral injury, significantly improve survival rate, cure rate and overall effective rate, reduce complications, significantly improve prognosis, and improve the quality of life of patients with severe craniocerebral injury. The mechanism of early hyperbaric oxygen therapy is: (1) Improving blood oxygen concentration, increase the diffusion of oxygen between tissues, and improve the hypoxia state of brain tissues; (2) Strengthening cerebral vasoconstriction, reduce cerebral blood flow, reduce vascular permeability, reduce exudation, reduce cerebral edema, and correspondingly reduce intracranial pressure; (3) Reducing blood viscosity, increase vertebrobasilar blood supply, improve hypoxia of brain stem and reticular activation system in the midline, promote the awake status, improve the life function activities, and facilitate the recovery of consciousness. (4) Reducing the production of free radicals, increase the stability of cell membrane, inhibit inflammatory reaction, and contribute to the resurrection of dormant cells and recovery of nerve function.

5. Conclusion

Cerebral edema occurred frequently after the severe brain injury because of the lake of oxygen in the brain, and STBI (severe traumatic brain injury) patients treated with hyperbaric oxygen therapy in the early stage can provide sufficient oxygen to prevent the brain from cerebral edema. In this research, brain edema occurs in patients with STBI shortly after the injury. This research found that usually 3-7 days after the injury is the peak period of cerebral edema. If edema is treated with HBO in time, it will always fade after one week because HBO provide enough oxygen to the brain. The conclusion can be summarized that STBI treated with adjuvant HBO in the early stage will be conducive to break the vicious cycle of brain edema - hypoxia – brain edema, and HBO has obvious effect and important significance for the early recovery of brain function. Clinical treatment experience has proved that the active hyperbaric oxygen treatment before the peak period of brain edema plays an important role in reducing brain edema, reducing intracranial pressure, improving the hypoxia state of brain tissue, improving blood supply of brain tissue, protecting the function of brain tissue and reducing the sequelae of severe brain injury. The clinical experiment discovered that the sooner patients with craniocerebral injury receive hyperbaric oxygen therapy; the more favorable it will be for patients’ condition improvement and sequelae reduction. And hyperbaric oxygen treatment in the early stage can strengthen cerebral vasoconstriction, increase oxygen partial pressure of blood, cerebrospinal fluid and brain tissue, reduce brain edema, cerebral ischemia and hypoxia, and maximally promote brain tissue recovery.

In this study, the observation group received early stage hyperbaric oxygen therapy on the basis of STBC plus tracheotomy. The total survival rate of the observation group was obviously higher than the control group. The recovery rate of the observation group was also better than that of the control group, suggesting that hyperbaric oxygen in early period can improve the prognosis of patients and gradually restore the function of incomplete nerve cells. In summary, under the precondition of strict control of indications and contraindications, early hyperbaric oxygen therapy combined with craniotomy decompression and removal of intracerebral hematoma can significantly reduce the disability rate and mortality rate of patients with STBI after surgery operation. It can substantially improve the patients’ life quality and greatly relieve the burden of patients’ family. The early hyperbaric oxygen therapy combined with craniotomy decompression and removal of intracerebral hematoma is a safe and reliable auxiliary treatment methodology with outstanding curative effect,rehabilitation effect, and good clinical prognosis, which is worth promoting extensively in the neurosurgeon departments of hospitals.

Abbreviations

 GCS    Glasgow Coma Scale Score

GOS     Glasgow Outcome Scale Score

KPS     long-term Karnofsky Performance Status Score

STBI    Severe traumatic brain injury

SLTC   standard large trauma craniotomy

HBO    hyperbaric oxygen therapy

Declarations

Ethics approval and consent to participate

Declaration by the Ethical Committee of 3201 Hospital Affiliated of Xi’an Jiaotong University .The ethical committee of the hospital have read the application and believe it to be scientifically and ethically sound. The committee approve the research design and give the consent for the implementation of the research in 3201 Hospital Affiliated of Xi’an Jiaotong University. Consent for publication.(number:201600189).All participants signed written informed consent.

Availability of data and materials

All data generated or analyzed during this study are included in this published article. I am willing to share my summarized data in a publicly available repository. The raw data of this research is not listed in detail because to list them all will occupy another too many pages in this paper, so I make a summarization about them and I wish to protect my patients’ detail privacy.

Competing interests

The authors declare that they have no competing interests.

Author’s contribution

  Firstly, professor G.S.W. has designed the research plan and research objective. Secondly, Dr.Z.L. and professor G.S.W. have done the clinical research, observed the treatment variety of patients, collecting research data, and analyzing the data. At the same time, Dr.L.J. helped record the change of patients and the process of the research. Finally, Dr.Z.L. wrote the manuscript and Dr.L.J. helped to do some proofreading and revising work.

Acknowledgement

  Hereby, the authors of this research would like to take this opportunity to declare sincere gratitude to the leaders of neurosurgeon department of 3201 hospital, who has provide substantial financial and equipment support for our research.

Funding

Not applicable.

Consent for publication

Not applicable.

References

  1. Stevens RD, Sutter R. Prognosis in severe brain injury. Crit Care Med. 2013;41(4):1104–23.
  2. Xu Liang Z, Xiangshuang W, Weidong, et al. Experience of standard large-bone flap craniotomy in 65 patients with severe craniocerebral injury. Journal of clinical neurosurgery. 2016;13(2):150–1.
  3. Yang Hualin Y, Yueli. Discussion on the curative effect of hyperbaric oxygen assisted treatment for 100 cases of severe craniocerebral injury. Journal of armed police logistics college (medical edition). 2013;22(5):431–2.
  4. Zengjun P, Yianwen Z, Shicong Z, et al. Journal of clinical neurosurgery. 2012;9(5):301–2.
  5. Tinghua Y, Jinhua J, Suiwan Lu, et al. Clinical study on the efficacy and anti-infection effect of early hyperbaric oxygen in the treatment of severe craniocerebral trauma. Chinese journal of advanced medical practitioners. 2014;37(14):60–3.
  6. Wang, Weiping, Tao zhen, Shao Xian’an, et al., 2012.Hyperbaric oxygen therapy on serum interleukin in patients with moderate and severe craniocerebral injury. IB and interleukin.6. Impact and efficacy analysis. Chinese journal of physical medicine and rehabilitation. 34 (7), 520–523.
  7. Rang Y, Zhang YG, Lin GA, et a1. The effects of different hyperbaric oxygen manipulations in rats after traumatic brain injury. Neurosci Lett. 2014;563(3):38–43.
  8. Xu Shaonian L, Jiachuan W, Jinbiao, et al. Early hyperbaric oxygen therapy for Cyt C, Bax and Bcl after craniocerebral explosion injury in rabbits.2. Influence of expression. Chinese journal of microinvasive neurosurgery. 2012;17(6):270–3.
  9. Liu dai, Huyin Y. Effects of hyperbaric oxygen on serum inflammatory factors, oxidative stress, endothelin and intracranial pressure in patients with severe craniocerebral injury. Journal of hainan medical college. 2017;23(5):651–4.
  10. Liu, Jinzhi. Clinical analysis of hyperbaric oxygen combined with standard large trauma craniotomy in the treatment of severe traumatic brain injury. Journal of guangxi medical university. 2017;34(1):80–2.
  11. Liu Baojiang W, Shouchen L, Guanglei, et al. Clinical analysis of hyperbaric oxygen combined with standard large traumatic craniotomy in the treatment of severe craniocerebral injury. Journal of clinical experimental medicine. 2013;12(9):673–5.
  12. Huang Liangzhen Fu, Chuanyi L, Qingzhi, et al. Comparison of the timing and efficacy of hyperbaric oxygen intervention in patients with craniocerebral trauma. Hainan medical science. 2016;27(19):3161–3.
  13. Wan Yulin X. Effects of high-pressure oxygen assisted standard large bone flap craniotomy on hemodynamics and serum inflammatory factors in patients with severe craniocerebral injury. Chinese general practice. 2017;15(4):568–70.