Clincial Research Of Early Hyperbaric Oxygen Treatment On The Patients After Craniortomy With Severe Traumatic Brain Injury

[Background]Traumatic brain injury (TBI) is called the silent epidemic of USA, and is a major cause leading to death or disability around the world. In China, severe TBI accounts for 20% of TBI. The mortality rate of TBI was 43% from 1988 to 1993, 36.8% from 1994 to 1996, and was 29.75% from 1997 to 2004. In the United States, the mortality rate of TBI decreased from 50% in 1970s to 17% in 2003 after various efforts. Overall, such a high mortality rate make TBI a serious burden to the family and society. The clinical outcomes of severe TBI are mainly depend on the molecular and cellular changes caused by secondary brain injure. These changes involves the pathophysiology of TBI.TBI can be classified into primary and secondary injury. Primary injury are just cerebral tissue damage such as cortex contusion and cerebral hemorrhage, but includes no extensive degeneration of neurons, other brain cells or axon. The patients' survival rate and mortality were decided by the progress of secondary brain injury. Secondary injure includes two aspects:1). Molecular responses after brain injury included release of excitatory amino acids, formation of free radicals and nitrogen oxides. The interaction among these three processes causes calcium influx into neurons, then damages the function of enzyme system and mitochondria, and results in apoptosis and disorder of ATP synthesis. At the same time, the formation of superoxide, free radical and nitrogen oxide interferes the metabolism and reproduction of cells, and leads to the structural and functional damage or even death of cells.2). Physiological changes after brain injury including:cerebral ischemia, vascular endothelial and blood-brain barrier damage because of subarachnoid and brain parenchyma hemorrhage, the subsquent instable homeostasis of internal envirement and lost of autoregulation, increased intracranial pressure (ICP) caused by hemorrahge, edema swelling or mass effect, TBI can cause cerebral edema, including interstitial edema (vasogenic) and the intracellular edema (cytotoxic).In China, patients with STBI are mainly treated by standard large trauma craniotomy, combined with post-operation dehydration, administration of corticoid, calcium antagonist and endogenous brain protector, as well as hypothermia, nutrition support, rehabilitation training and application of analeptic. In abroad, certain interventions were given according to corresponded mechanisms of TBI to reduce the mortality and disability rate. But various drugs and hypothermia multicenter clinicaltrials have failed to show improvement in functional outcome and mortality rates in patients suffering from TBI. However, recent animal studies and clinical trials have shown potential value of the field of oxygen therapy especially hyperbaric oxygen (HBO) for the treatment of severe TBI. As the development of techniques and instruments for animal experiments and clinical researches, HBO appears to work on mitochondria level to improve cerebral aerobic metabolism after brain injury in animal studies. Clinical studies found that HBO could reduce the mortality rate of TBI and improve the functional outcome. HBOT has a history more than two hundred years. Recommended by Undersea and Hyperbaric Medical Society (UHMS) in 1999, it is widely used clinically in the treatment of carbon monoxide poisoning, gas gangrene and decompression disease. Along with the promotion of HBO, new indicators were added by UHMS in 2000, such as acute cerebrovascular disease, brain edema and TBI. Application of HBO for treatment of TBI develops rapidly. A lot of researches found that mechanism of HBO T were complicate and corresponded to the pathophysiologic changes of TBI.Previous studies found that the mechanism of HBO contained:1). HBO caused cerebral vasoconstriction that reduced cerebral blood flow (CBF), ICP and edema, and increased bioavailability of oxygen on the cellular level, then release the ischemia because of incrasing oxygen delivery 2). HBO could improve ICP and had persistent effect on ICP after the treatment.3). HBO could stabilize blood brain barrier.4). HBO could improve the glucose metabolism and aerobic metabolism of STBI patients on the mitochondrial level.5). Research in mouse discovered that HBO could promote the recovery of cognition, increase cerebral ATP level and reduce the loss of hippocampal neurons.Many studies were went on to investigate HBO for treatment of TBI, and had some positive achievement. Single experimental or clinical study suggests that the treatment is effective. But a meta-analysis by Oregon Evidence-Based Medicine center said:"The evidence for HBOT for TBI is insufficient to prove effectiveness or ineffectiveness". Only a few studies were taken to evaluate the effect of HBOT on post decompressive craniotomy. A German clinical research measure ICP and cerebral tissue oxygen level before, during and after decompressive craniotomy, in 11 patients showed that decompressive craniotomy could improve the ICP and brain tissue oxygen level in diffuse brain edema and brain mass during and after the operation. A perspective multicenter clinical trial also showed that after the decompressive craniotomy, the brain tissue bulged into the bone window, then compensate the intracranial volume, released the mass effect and the compression of brainstem, then protected the brain effectively. The volume change recovered the brain structure, improved the delivery of blood and oxygen, led to a better outcome of patients.In the previous studies on HBO for treatment of STBI, patients suffered from brain contusion, laceration, brainstem injury and diffuse axon injure yet not receiving craniotomy were also included. On one hand, patients with brain contusion, laceration and edema were treated conservatively. So that the brain mass effect was not improved. Then the insufficient local delivery of blood and oxygen induced brain ischemia. On the other hand, patients with brainstem injure or diffuse axon injury were always in coma for a long time. Last but not least, the skull was incomplete after craniotomy, and ICP prone to fluctuations, especially during the situation of coughing, fevering or position change. These situation has a serious interfere with the assessment of HBO therapy. According to these, we focused on the STBI patients post decompressive craniotomy to assess the outcome of HBO. Adopted the Glasgou Coma Scale(GCS) and Glasgow Outcome Scale (GOS) to assess the effection on improving the patient's awareness and prognosis of HBO. Researchers in the past only used the pulmonary infection as the indicator with HBO treatment to evaluate the effection for airway restoration.In this study, we introduced the removal rate of tracheal tube in patients with tracheotomy to integrated assessment of airway recovery.[Objectives]1. To observe the effect of early HBOT on the state of consciousness improved (GCS improvement) for TBI patient post decompressive craniotomy.2. To assess the changes of prognosis (GOS improvement) of the two groups patients when they finish the course of HBOT (five weeks after admission) and three months after admission.3. To assess the effect of HBOT on airway restoration (the removal rate of trachea cannula) in STBI patients post decompressive craniotomy with tracheotomy.[Methods]1. This study was a cohort study. Sixty-one patients who admitted in Huadu District People's Hospital from Jan.1,2009 to Nov.25,2010 were included. All of them received large trauma decompressive craniotomy. The time of inclusion was seven days after the craniotomy.2. Criteria for inclusion:①Aged between 18 to 60,②Suffered with severe TBI, The Admission GCS score(GCSO) between 3 to 8,③Receiving large trauma decompressive craniotomy in 24 hours after admission.④The patient had stable vital signs one week after admission and were able to tolerate HBO treatment.⑤Whether perform HBOT or not decided by patients' family, then signed Informed Consent of Treatment. Criteria for exclusion:unable to complete the course of HBOT.3. Finally 61 patients were included based on randomized clinical trials program (random number table), the selected patients in the hyperbaric oxygen treatment group of 30 patients, and in the control group (non-HBOT group) 31 cases.①HBO treatment group:Twenty-four patients were male and six were female. Median of age were 35 (18 to 60). Average weight 60.57±8.61 kg. Average height 165.97±8.09 cm. Average GCS score at admission 6.10±1.42. Average GCS score before HBO 7.47±1.61. twenty-one patient received tracheotomy and nine didn't. twenty-two patients suffered from brain hernia and eight didn't. The contribution of cause of injury was twenty-five traffic accidents, two blunt force injury and three fall injury. Preoperative diagnosis were all STBI. Postoperative diagnosis were:three brain contusion with intracerebral hematoma, fourteen brain contusion with subdural hematoma, four brain contusion with epidural hematoma, one epidural hematoma and eight composite hematoma.②Control group:Twenty-four patients were male and seven were female. Median of age were 36 (19 to 60). Average weight 61.16±8.59 kg. Average height 166.61±6.99 cm. Average GCS score at admission 6.23±1.52. Average GCS score before HBO 7.87±1.31. twenty-one patient received tracheotomy and ten didn't. twenty-two patients suffered from brain hernia and nine didn't. The contribution of cause of injury was twenty-seven traffic accidents, two blunt force injury and two fall injury. Preoperative diagnosis were all severe TBI. Postoperative diagnosis were one brain contusion with intracerebral hematoma, fourteen brain contusion with subdural hematoma, six brain contusion with epidural hematoma, three subdural hematoma,twoepidural hematoma and five composite hematoma.4. All patients have given emergency surgical treatment of decompressive craniectomy after them admitted to hospital. They were given monitoring for cardiac electrical activity and oxygen saturation in early postoperative. In addition, oxygen inhalation and drugs for dehydration, hemostatic, protection of gastric membrance, prevention of infection, neurotrophic, energy,water and electrolyte supplement and supportive care were used. Tracheotomy were given in 4 days after admission when needed. CT scan of head were performed about a week after surgery to them, and microcirculation improving durgs were used when clearly knew no active bleeding. If vital signs were stable about 7 days after admission, patients were treated with HBO 28 times in the Department of HBO. The control group received the same treatment excluding hyperbaric oxygen therapy.5. Observation indexes:①GCS scores of patients in two groups at admission 1,2,3,4 and 5 weeks after admission.②GOS of the patients before HBO therapy, after HBO therapy (5 weeks after admission) and three months after admission. GOS was divided into 5 states:1. Dead,2. Vegetative state,3. Severe disability,4. Moderate disability,5. Good recovery.③The numbers of patients that has their trachea cannula removed 5 weeks and three months after admission.6. Statistical Methods:Use SPSS 13.0 statistical analysis software. we entry all patients' relative data after information collection and processing. Then make the appropriate statistical description and testing. Normal distributed data were described as Mean±SD and were compared using two-sample t-test, non-normal distributed data were described as mean rank and sum of ranks, and were compared using two-sample Wilcoxon rank sum test. Enumeration data were described as rate and were compared by Chi-square (χ2) test. P<0.05 was considered as statistically different.[Results]1. The general describe and test of the baseline data for the two groups of 61 patients (21 patients in each group tracheotomy). Use corresponding statistical tests for the variables [Age, GOSb;gender, tracheotomy, admission hernia, injury cause; height, weight, admission GCS score, before HBOT(about admission 1 week)GCS score]. all P value> 0.05, the baseline datas variables showed no significant difference. The baseline information on the two selected groups patients were balanced well.2. The GCS score between two groups showed no significant difference in two weeks after admission (t=1.684, P=0.097). However, in 3 weeks after admission GCS score (t=2.091, P=0.041),4 week GCS scores (t=2.240, P=0.029),5 week GCS scores (t=2.759, P=0.008), all of them showed significant differences.3. Compared GOS5w with GOSb,the number of patients GOS improved (named:iGOS5w). compared GOS3m with GOSb,the number of patients GOS improved (named:iGOS3m). Test the variables (iGOS5w,iGOS3m)respectively between the two groups. Chi-square (χ2) test results suggest that between two groups iGOS5w was significant difference (χ2=4.725 P=0.030), iGOS3m also showed significant differences (χ2=5.191 P=0.023).4. Use chi-square test respectively in two stages (5 weeks after admission and 3 months after admission),for the difference on removal rate of trachea cannula between two groups. The results suggestted that 5 weeks after admission, between two groups the number of cases on trachea cannula removed was a significant difference (χ2=8.005, P=0.005; Fisher's Exact Test P=0.011), but 3 months after admission have no significant difference (χ2=3.500, P=0.061).[Conclusions]1. Early HBOT can promote the improvement of the consciousness in STBI patients post decompressive craniotomy.2. Early HBOT can obviously promote the improvement of the outcome in STBI patients post decompressive craniotomy.3. HBOT can promote airway restoration, and contribute to the removal of trachea cannula in the early phase more than in the late phase in severe TBI patients post both decompressive craniotomy and tracheotomy.