Epidural hematoma (EDH) is a potentially serious but treatable sequel of head injury. The incidence of EDH in the population with traumatic brain injury (TBI) has been reported to be in the range of 3% - 4%     and the peak prevalence of EDH is in the second decade of life. EDH is usually unilateral in more than 95% of cases, however bilateral or multiple are also reported which account for 2% - 5% of all acute epidural hematomas in adults     .
Computed Tomography (CT) scan has been adopted as primary choice of investigation in the evaluation of suspected intracranial epidural hematoma   . The preoperative radiological parameters, such as hematoma volume, degree of midline shift, presence of additional intracranial lesions and neurological status of the patient, have been reported to influence the outcome of EDH   . Patients with EDH who meet surgical criteria and receive surgical treatment can have an excellent prognosis presumably owing to limited underlying primary brain damage  . Although craniotomy provides more complete evacuation of the epidural hematoma, there are insufficient data to support one particular surgical treatment method   . Recently minimal invasive technique has been attempted and valuable outcomes were reported in various literature. It is reported that burr hole evacuation followed by drainage under negative pressure is a safe and effective method for emergency management of pure traumatic epidural hematoma  . Furthermore, the twist drill trephination and installation of Urokinase has been described as useful in selective patients without any casualties   . It is demonstrated that the use of Urokinase promotes clot lysis and resorption without producing neurotoxicity, histopathological alterations or recurrent bleeding  . The fibrinolysis technique has emerged as the most promising surgical modality that has been proved to be safe and effective treatment option for lysis of subarachnoid blood, intraventricular hemorrhage, intracerebral hemorrhage     and traumatic epidural hematoma   . This study presents novel method of evacuating traumatic EDHs using single burr hole with Urokinase instillation in different time intervals.
2. Materials and Methods
Forty-two patients (n = 42) range between 15 to 71 years old (mean age 34 ± 16.30) were diagnosed as traumatic epidural hematoma with CT scan. All patients were surgically treated in the First Affiliated Hospital of Liaoning Medical University from January 2013 to June 2015. Among these population 33 were male and 9 were female. Road traffic accident was the major cause of trauma followed by physical assaults. The Glasgow Coma Scale (GCS) score were 8 to 15 during admission. All the medical records and case materials were retrospectively reviewed. Coagulation profile such as Hematocrit, Platelet count, activated Partial Thromboplastin Time (aPTT), Prothrombin Time and International Normalized Ratio (PT/INR), Bleeding Time(BT) and Clotting Time(CT) was also reviewed which were within normal range. CT scans were analyzed; hematoma location, size and associated mass effect and parenchymal injury were also carefully assessed.
Inclusion criteria: GCS ≥ 8, Clear history of trauma, Single hematoma lesion, Supratentorial hematoma, Midline shift ≤ 1cm and Informed consent from patient.
Exclusion criteria: GCS < 8, Patient with Polytrauma, Coagulation disorder/ coagulopathy, Depressed skull fracture, and Previous history of stroke; intracranial aneurysm; AV malformation.
Informed consent was taken from the patients who met the inclusion criteria. Patients were allocated into two groups: Group A―surgery within 3 - 5 days of onset and Group B―surgery beyond day 5. Patients were categorized according to their general condition, stability, neurological status and CT findings: blood volume, thickness and midline shift during admission (Table 1). The preferred surgery day was selected according to pathophysiology of hematoma liquefaction  . According to Hideo et al., epidural hematoma begins degenerative changes in 3 to 5 day of onset. Within 6 to 10 days blood often become partially clotted and crumbly and usually liquefies at 25 - 30 days  .
2.1. Treatment Method
All patients received intravenous antibiotics on the day of surgery followed by four consecutive days. Patients were shifted to the operation room. Under local anesthesia, single burr hole was drilled over the largest hematoma area according to CT scan scale. Hematoma was allowed to flow out itself and visible clot was removed to create some space for the drain and to instill Urokinase without fur-
Table 1. Computed tomography findings and group division of traumatic epidural hematoma.
ther increase in intracranial pressure. Draining tube was connected to compressible drain bulb with 3-way stopcock. The minimal negative pressure created by the compressing bulb helps the liquefied hematoma to drain easily. After an hour of surgery, no drainage of fresh blood was confirmed and 30,000 - 50,000 IU of Urokinase dissolved in 3 - 4 ml of normal saline was injected into the epidural cavity via 3-way stopcock. Another 3 ml normal saline was pushed to flush the tube. Drainage tube was occluded for 2 - 3 hours based on clinical manifestation of the patient and then released. During this time period patients were advised to change the head position often to spread the injected Urokinase all over the cavity and allow early dissolution of clots. The Urokinase was used twice a day for 2 - 3 days based on the patient tolerance and the CT findings. According to the changes in patient clinical manifestation and daily collection in the drain CT scan was performed every 24 hours to check the left over hematoma in epidural space. The drainage tube was not removed until all the clots were resolved as suggested by CT scans. Urgent studies were performed if an acute neurological deterioration was recognized.
2.2. Static Analysis
Statistical analysis was conducted using SPSS 20.0 software. The outcome between two groups is analyzed using Pearson’s Chi square test. P values < 0.05 were considered to indicate statistical significance.
In this study time for detecting hematoma after trauma was 2 - 5 hours (mean 3.14 ± 1.26 hour). The mean time of surgery in group-A was 3.57 ± 0.74 day and in group-B 6.19 ± 0.60 day. Of all 42 included cases, site of hematoma located in temporal region were 23 (54.7%), 12 (28.5%) in frontal, 5 (11.9%) in temporo- parietal and 2 (4.7%) in occipital region (Table 2). The common complication encountered following the use of Urokinase was headache, dizziness, fever and re-bleeding (Table 3). In Group-A, 4 (19%) patients complained of headache, 5 (23.8%) dizziness, 1 (4.7%) fever, and re-bleeding occurred in 2 (9.5%) patients in which one had on first day and another on third day of use of Urokinase. In Group-B, 2 (9.5%) patients complain of headache, 1 (4.7%) dizziness, 1 (4.7%) fever and re-bleeding in 1 (4.7%) patient on the first day of Urokinase use.
The nature of headache was mild and the fever was low grade. Fever was treated with intravenous Dexamethason whereas headache was alleviated by release of occluded drain. It is believe that when fibrinolytic activity takes place the expansion phase of the clot occurs causing some degree of fluctuation in intracranial volume and pressure, resulting headache  . Patients with re-bleeding complained of severe pulsatile headache and gradually neurological deterioration occurred leading to immediate conventional craniotomy. At once patient was shifted to Operation Theater. Under general anesthesia craniotomy was performed. The volume of hematoma was near double compare to prior urokinase use. Patient from the group A who re-bleed on third day of urokinase use
Table 2. Site of Extra Dural hematoma.
Table 3. Complication of the treatment.
X2 = 4.842, p < 0.028.
was tolerating urokinase for two day. Neurological status was improving but on the third day patient suddenly deteriorated.
The pathophysiology of epidural hematoma is that the sequences of cellular response pace exist between different individuals. According to Hideo et al., the first sprouting of fibroblasts from the outer layer of the dura into the epidural blood clot occurs after 2 to 3 days and gradually the fibroblast layer becomes slightly thicken by few cell layers which begins to enter the clot after 3 to 5 days. Then few erythrocytes may demonstrate degenerative changes. Within 6 to 10 days blood often become partially clotted, crumbly and develops a dark brown color. When hematoma reaches to 25 - 30 days blood usually liquefies  . During this process solid hematoma liquefie and begin to detach from one particular point or from the area of injured portion. The natural process of transforming the clot facilitates to remove the epidural hematoma effortlessly using Urokinase.
Urokinase is a strong plasminogen activator which specifically cleaves proenzyme/zymogen plasminogen to form active enzyme plasmin and active plasmin is able to break down the fibrin polymers of blood clots    . Before the commencement of thrombolytic therapy obtaining coagulation profile is essential and need to be within the normal range. Patient who exhibit reactions
Figure 1. Axial view of Head CT. (A) EDH in right temporal region prior to surgery; (B) 2nd postoperative day with tube in situ; (C) 3rd postoperative day with tube in situ; (D) 5th postoperative day prior to discharge.
Figure 2. Axial view of Head CT. (A) EDH in left temporal region prior to surgery; (B) & (C) 1st postoperative scan with tube in situ where size of hematoma increases after instillation of urokinase with mass effect; (D) Post craniotomy scan.
should be refrained from the treatment, closely monitor and appropriate therapy must be use. Antipyretics such as aspirin and other non-steroidal anti-inflam- matory agents which inhibit platelet function may increase the risk of bleeding and should not be used for the treatment of fever during Urokinase use   . Following demonstration of clot lysis effect without producing neurotoxicity, histopathological alterations or recurrent bleeding in an animal model by Narayan et al.   , fibrinolysis technique has emerged as the most promising surgical modality. It has been proved safe and effective treatment option for subarachnoid hemorrhage, intraventricular hemorrhage, intracerebral hemorrhage     and traumatic epidural hematoma    .
The clinical presentation of epidural hematoma somewhat is variable with the mechanism of injury or the site of lesion. Once the diagnosis of epidural hematoma has been made surgical evacuation is usually the standard treatment procedure to prevent mortality or neurologic morbidity. Not all cases of acute EDH require immediate surgical evacuation   . If the lesion is too small and patient is in good neurological condition observing patient with frequent neurological examinations is reasonable. Recently non-surgical management of small EDH is increasingly accepted with lesions not associated with mass effect or midline shift   . Most of the small to moderate EDHs resolves spontaneously in few weeks to few months   . Bullock et al. reported that the resolution of hematoma took 3 - 15 weeks in the conservative management  . During the conservative management the reabsorption phase is always accompanied with expansive phase of clot due to fibrinolytic activity and in some cases latter phase may be predominant  . The major drawback of conservative treatment is prolong inpatient close monitoring and always remains high chance of re-bleeding.
The decision to perform surgery in patient with traumatic extradural hematoma is depend on neurosurgical judgment. Hematomas volume, secondary mass effect and clinical judgment have been commonly accepted as major criteria for surgery  . Patients with EDH who meet surgical criteria and receive surgical treatment can have an excellent prognosis presumably owing to limited underlying primary brain damage  . Although craniotomy provides an effective evacuation of hematoma there is insufficient data to support one particular surgical treatment method   . A small number of minimally invasive methods have been reported in the literature for the management of EDH in certain circumstances and satisfactory outcome was reported. Noguchi et al., 2010, reported that neonatal EDH is more liquefied than adult counterpart and is amenable to needle aspiration under transcranial ultrasound guidance for massive EDH seen following vacuum-assisted delivery  . Also, aspirating cephalhematoma to evacuate communicating epidural hematoma in a newborn infant with no neurological signs has been successfully employed to avoid more invasive surgical intervention by Smets and Vanhauwaert, 2010  . In a clinical series reported by Liu J.T. et al., 2006, 11 of 13 patients harboring traumatic EDH were successfully treated by placement of flexible tube through burr hole followed by continuous suction under negative pressure, and only two cases required secondary craniotomy  . The novel method of Urokinase instillation using closed suction drain has been proposed for post-craniotomy epidural hematoma as a feasible method with no complication and better outcome by Park et al., 2008  . And drilling the skull with instillation of Urokinase into hematoma space has been reported in 22 selected cases of traumatic EDH without complication by Liu W. et al., 2008  .
Beside some limitation instillation of Urokinase is effective in selective cases. This study may not be favorable in acute stage of traumatic epidural hematoma due to the higher chances of rebleeding that might aggravate the condition. The tamponade effect of blood clot play certain role to stop bleeding during trauma  . Therefore early exposure of Urokinase may dissolve the tamponade of the injured vessels sustaining the risk of re-bleeding. Some authors have suggested that by the time of presentation EDH is relatively stable lesion having attained maximum size within minutes of injury     . Borovich et al. demonstrated progression of epidural hematoma in 9% of patients during the first 24 hours  . Thus repeated CT scan should be done at least ~6 to 12 hours of injury followed by every 24 hours. The maximum volume, thickness and midline shift operated in this study was 60 ml, 40 mm and 10 mm respectively. Therefore only hematoma volume is not always the primary indication for early craniotomy. On the basis of our experience we should pay attention to the Urokinase use although there is no overwhelming consensus on the dose. It should be administered gradually in the reduction dose correlating with CT finding to avoid recurrence of bleeding. Strict sterilization procedures need to be maintained. No any neurological deficit or mortality was found throughout the treatment and a year of regular follow up.
This study demonstrated that single burr hole with Urokinase instillation is safe, feasible and effective technique in the treatment of traumatic intracranial epidural hematoma in selected cases, especially, for the symptomatic patient with GCS greater than eight without signs of cerebral herniation, where close regular clinical and radiological monitoring is accessible. The use of Urokinase is feasible in both groups, however Group B has better outcome than Group A and is statistically significant (P < 0.028).
Written informed consents were obtained from the patients for publication of this article and any accompanying images.
The authors have no proprietary or financial interest in any materials discussed in this work.
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