Impact of Time from Injury to Surgery on Postoperative Functional Recovery in Large Volume Traumatic Extradural Hematomas

Abstract Background  In traumatic brain injury (TBI) patients, the time from trauma to cranial surgery is always of great concern to patients and neurosurgeons. Patients and Methods  A retrospective study conducted on 93 TBI patients presented with Glasgow Coma Scale from 4 to 13 and were operated for large volume (≥ 40 cm 3 ) extradural hematoma (EDH) from July 2020 to December 2022. Surgery was done either within 6 hours following trauma (group A) or later than 6 hours (group B). We evaluated the impact of time from injury to surgery on postoperative clinical recovery, survival, and hospital stay. Results  Fifty patients (53.8%) were operated upon within 6 hours after trauma and 43 patients (46.2%) had operations later than 6 hours. No significant difference was found between the two study groups regarding any of the preoperative clinical or radiological factors except for the mean time from injury to surgery ( p  < 0.001). Delayed surgery > 6 hours was significantly associated with higher postoperative mortality ( p  = 0.014). Hospital stay was significantly shorter in patients operated ≤ 6 hours ( p  = 0.006). Patients operated ≤ 6 hours showed significantly favorable functional recovery both at discharge ( p  = 0.010) and after 1 month of follow-up ( p  = 0.023). Conclusion  Timely surgical intervention for large volume traumatic EDH is the gold standard. Early surgery “within 6 hours from trauma” not only can save patients' life but also is significantly associated with postoperative favorable clinical recovery, low morbidity, and short hospital stay.


Introduction
Head injury is a major health problem with high risk of morbidity and mortality. 1,2Among intracranial hematomas, extradural hematoma (EDH) assumes the greatest importance as it can be easily diagnosed and treated.For large volume EDH, craniotomy and hematoma evacuation is the only way to save patients' life from a potentially fatal benign lesion. 3,4rious factors can be of prognostic value in patients with traumatic EDH including: age, the Glasgow Coma Scale (GCS), pupillary abnormalities, hematoma volume, midline shift (MLS), time from injury to surgery, and secondary brain insult (hypotension, hypertension, or hypoxia). 5,6In computed tomography (CT) scans, associated intracranial lesions such as subdural hematoma (SDH), intracerebral hematoma (ICH), subarachnoid hemorrhage (SAH), or cerebral contusion may result in an increased mortality rate. 7,8ywords ► extradural hematoma ► head injury ► surgical evacuation ► time from injury to surgery ► postoperative recovery

Abstract
Background In traumatic brain injury (TBI) patients, the time from trauma to cranial surgery is always of great concern to patients and neurosurgeons.
Patients and Methods A retrospective study conducted on 93 TBI patients presented with Glasgow Coma Scale from 4 to 13 and were operated for large volume (! 40 cm 3 ) extradural hematoma (EDH) from July 2020 to December 2022.Surgery was done either within 6 hours following trauma (group A) or later than 6 hours (group B).We evaluated the impact of time from injury to surgery on postoperative clinical recovery, survival, and hospital stay.
Results Fifty patients (53.8%) were operated upon within 6 hours after trauma and 43 patients (46.2%) had operations later than 6 hours.No significant difference was found between the two study groups regarding any of the preoperative clinical or radiological factors except for the mean time from injury to surgery (p < 0.001).Delayed surgery > 6 hours was significantly associated with higher postoperative mortality (p ¼ 0.014).Hospital stay was significantly shorter in patients operated 6 hours (p ¼ 0.006).Patients operated 6 hours showed significantly favorable functional recovery both at discharge (p ¼ 0.010) and after 1 month of follow-up (p ¼ 0.023).Conclusion Timely surgical intervention for large volume traumatic EDH is the gold standard.Early surgery "within 6 hours from trauma" not only can save patients' life but also is significantly associated with postoperative favorable clinical recovery, low morbidity, and short hospital stay.
In the daily neurotrauma practice, the time from injury to surgery is of great concern to patients and neurosurgeons; however, in literature there remains little data evaluating the association.Hence, we carried out this retrospective study to evaluate the impact of time from injury to surgery on postoperative functional recovery in traumatic brain injury (TBI) patients, operated for large volume EDH.

Study Design and Patients' Population
A retrospective observational study, conducted on TBI patients who underwent craniotomy and evacuation of acute large volume EDH in our institution in the period from July 2020 to December 2022.This study was approved by the local ethical scientific committee of our institution (IRB approval number: 4-2023.NEUS 4-1).Head injury patients of either sex with no age restrictions who presented with GCS score (4-13) and had acute EDH with volume !40 cm 3 on brain CT scan were included in our study.We excluded patients with (1) GCS score 14 or 15, (2) GCS score 3 with bilateral dilated fixed pupils, (3) concomitant posttraumatic intracranial hemorrhagic lesions (SDH, ICH, SAH, or cerebral contusion), and (4) associated other significant systemic injury that affected the hospital course.In regards to the time interval from head injury to EDH evacuation, operations were done either within the first 6 hours after trauma (group A) or later than 6 hours (group B).

Data Collection
Demographic, clinical, and radiographic data were collected from patients' medical records of our department including data on and during the period of admission and then follow-up data during the first month after discharge.Preoperative data included: age; sex; mechanism of trauma including road traffic accident (RTA), fall from height (FFH), or assault; GCS on admission; clinical signs (pupillary responses and contralateral hemiparesis); coagulopathy; EDH side, location, volume, and maximum thickness; degree of MLS; concomitant intracranial lesions; and time from trauma to the beginning of surgery.
Postoperative data included: GCS after surgery and at discharge, neurological deficits, findings in follow-up CT scans, operative-related complications, hospital course, and discharge outcome.
EDH volume was calculated in three dimensions.The width was measured as the transverse diameter, the length as the anteroposterior diameter, and the depth as the superoinferior diameter.Approximated volume was computed by multiplying the three dimensions using the Petersen and Espersen 9 equation: volume ¼ ABC / 2.

Management
Resuscitation efforts were carried out for all patients, including assessment and stabilization of airway patency, breathing, and circulation.After confirming the diagnosis with CT brain, patients were shifted to the operating room where surgical evacuation of the EDH was done by the neurosurgical team on duty.Postoperatively, patients were kept under close neurological observation; routine follow-up CT brain was done during the first postoperative 24 hours and just before discharge, while it was done on urgent basis once indicated.

Outcome Measures
The two study groups were compared regarding postoperative clinical recovery and improvement, complications, survival, and length of hospital stay.The Extended Glasgow Outcome Scale (GOSE) score demonstrated in ►Table 1 is a measure of the association between traumatic injuries and diverse aspects of daily functioning. 10GOSE score was measured at discharge and 1 month later.Patients who had moderate disability or good recovery (GOSE score from 5 to 8) were included together in the favorable functional recovery group while patients who were severely disabled, vegetative, or died (GOSE score from 1 to 4) were included together in the unfavorable recovery group.

Results
A total of 112 TBI patients were diagnosed with acute large volume EDH that required urgent surgical evacuation; 19 patients were excluded (10 patients presented with GCS score 14 or 15, 1 patient presented with GCS 3 and bilateral dilated fixed pupils, 3 patients had concomitant intracranial hemorrhagic lesions, and 5 patients had associated significant systemic injury).So, 93 patients were actively included in our study.In regards to the time from injury to surgery, 50 patients (53.8%) were operated upon within the first 6 hours after trauma and 43 patients (46.2%) had operations later than 6 hours.
In the entire sample, the mean GCS score on presentation was (9.87 AE 2.401).The majority of patients (76.3%) had GCS score of 9 to 13 and 23.7% had GCS score of 4 to 8.Although the number of patients with low GCS was higher in group B 13 cases versus 9 cases in group A, this difference was statistically nonsignificant (p ¼ 0.166).
The mean patients' age was 24.70 AE 12.107 years with a range from 2 to 59 years.►Fig. 1 illustrates the distribution of included patients among different age groups.The majority of patients (67.7%) were males.The most common mechanism of injury was RTA (55.9%) followed by FFH (31.2%) and assault (12.9%).In regards to preoperative examination, 16 patients (17.2%) had anisocoria and 21 patients (22.6%) presented with contralateral hemiparesis.Eight patients (8.6%) had preoperative coagulopathy.►Table 2 compares the general and clinical data between patients of the two study groups.
Noticeably, there was no significant difference between the two study groups regarding any of the preoperative  clinical or radiological factors except for the mean time from injury to surgery (p < 0.001).►Table 4 displays the postoperative results in the entire sample and compares the results between the two study groups.Postoperative complications were encountered in 7 cases (7.5%).Five cases required resurgery, three cases were reoperated for recurrent EDH, one for large postoperative residual EDH, and one underwent decompressive craniectomy for massive postoperative cerebral infarction.
As illustrated in ►Fig.2, the GOSE score was significantly higher in patients operated 6 hours both at discharge and 1 month after surgery (p ¼ 0.016 and 0.043, respectively).
As demonstrated in ►Table 5, time from injury to surgery was the only independent predictor with significant impact on postoperative functional recovery.

Discussion
EDH is considered a serious neurosurgical emergency following TBI.Despite the advances in prehospital and inhospital management for trauma patients, there are still relatively high rates of morbidity and mortality in patients with large volume traumatic EDH. 11,12n our case series, 50 patients (53.8%) underwent surgical evacuation for their EDH in 6 hours following trauma with a mean time to surgery of 4.210 AE 1.270 hours and 43 patients (46.2%) had operations later than 6 hours with a mean time to surgery of 10.962 AE 3.440 hours.Worth mentioning, that delayed arrival of TBI patients to our emergency department after trauma was behind the delay in surgery.
In point of fact, previous studies showed considerable variance in the time from trauma to EDH surgery; this variance can be explained by the differences in the time of EDH diagnosis and/or the time of patients' reception.Khaled et al 5 found that the time interval between trauma and surgery was within 13 to 24 hours in 54% of their cases.In

Time to Surgery and Postoperative Hospital Course
In our series, long time from injury to EDH evacuation showed a negative feedback on postoperative hospital course, where surgery done later than 6 hours after trauma was associated with a high risk for postoperative cerebral infarction, higher rate of mortality, and longer duration of hospital stay.We encountered two cases (4.7%) that developed postoperative cerebral infarction and both of them had delayed surgery > 6 hours.This can be attributed to the longer brain tissue compression by the large hematoma volume that can result in increased intracranial pressure and disturbed cerebral autoregulation leading to impairment of cerebral blood flow and cerebral perfusion.Also, this may be related to a secondary brain insult such as uncontrolled blood pressure or hypoxia that may develop following TBI.
Also, delayed EDH evacuation was significantly associated with higher postoperative mortality (p ¼ 0.014).Among the 43 patients who had delayed surgery >6 hours after trauma, 7 patients (16.2%) expired.In agreement with our result, Ozkan et al 16 in their retrospective analysis reported that mortality rate was 23.5% in patients operated later than 6 hours of injury.Also, in the series of Das et al 12 55 patients (3%) expired, all of whom had time between injury and surgery of more than 12 hours.On contrary to our results, Lafta et al 17 reported that the time interval between injury and patient reception had no effect on mortality.This difference from our results can be attributed to: in their series, 46% of patients had the time interval between injury and reception of <3 hours and 38% of received patients presented with high GCS.
In our study, time to surgery proved to have a significant impact on the length of postoperative hospital stay.Patients who had surgery 6 hours showed a significant short length Fig. 2 The correlation between time from injury to surgery and the Extended Glasgow Outcome Scale (GOSE) score at discharge (A) and after 1 month (B).Short time from injury to surgery was a significant predictor for higher GOSE score (p ¼ 0.016 and 0.043 at discharge and after 1 month, respectively).
of hospital stay (p ¼ 0.006).No previous studies addressed the association between time to EDH surgery and length of hospital stay.

Time to Surgery and Postoperative Functional Recovery
At discharge, 70 patients (75.3%) showed favorable functional recovery while 23 patients (24.7%) showed unfavorable recovery, including 8 patients who expired.One month after surgery, the percentage of favorable recovery was increased to 89.4%.In literature there is agreement that despite being a serious neurosurgical emergency, EDH mostly carries a good prognostic outcome after surgery. 2,11,14,18,19►Fig. 3illustrates the pre-and postoperative CT scans of a patient who was operated upon for large volume EDH within 6 hours after trauma and despite of having a low GCS on presentation, this patient had postoperative favorable recovery.
Although there was no significant differences between the two studied groups regarding the preoperative clinical or radiological parameters, we observed significantly favorable postoperative functional recovery both at discharge (p ¼ 0.010) and after 1 month of follow-up (p ¼ 0.023) in patients operated 6 hours following trauma.This finding signifies the golden value of the short time from injury to surgery in achieving favorable postoperative outcome.
There is a wide consensus among previous studies about the importance of early surgery for EDH patients.In Niaz et al 14 study, almost 70% of patients were operated within 6 hours of injury and all of them ended up with good outcome, while in the 30% with delayed surgery >6 hours, 63.7 and 36.3% had poor and good outcome, respectively (p < 0.001).Niryana et al 20 reported that preoperative duration !12 hours was a pure risk factor for unfavorable outcome.Korinth et al 21 mentioned that delayed EDH treatment would result in a poor outcome.Lafta et al 17 reported that better functional recovery (p ¼ 0.001) was found among patients with a shorter time interval between injury and patient reception ( 3 hours).Also, in the series of Das et al, 12 all patients (100%) who were operated within 12 hours of injury achieved good outcome, while 94% in whom surgery was done between 12 and 24 hours achieved good outcome and only 64% of those who were operated beyond 24 hours ended up with good outcome.Time to Surgery in Extradural Hematomas Elkholy et al.
In contrast to our results, the study of Ayogu et al 2 failed to demonstrate an association between outcome and the time interval from trauma until surgery.Patients operated upon within the first 6 hours of presentation did not show a significantly better outcome when compared with patients who had surgery later than 6 hours (p ¼ 0.083).Also, Nnadi et al 18 reported that time to surgery did not have significant effect on the outcome (p ¼ 0.760).The difference between our results and these studies can be explained by the high percentage of patients with mild TBI and high GCS score (13-15) who were included in these studies; 51 and 38% in Ayogu et al 2 and Nnadi et al 18 study, respectively.
In regards to the factors that can influence the postoperative functional recovery, the prognostic impact of patients' age, preoperative anisocoria, admission GCS, and hematoma volume have been studied most frequently in previous studies. 12,14,17,20,22,23In our series, none of these factors was a significant predictor for favorable functional recovery.
Concerning patients' age, the majority of patients (58.1%) were young adults (age 21-40 years) and only 2.2% were > 50 years; this was behind the reduced impact of patients' age on the postoperative outcome.Preoperative anisocoria was reported in a small number of our patients (16 cases) and 7 cases of them were operated 6 hours after trauma.No doubt that the GCS on admission has an important role in the prognosis of EDH patients.In the current study, patients with GCS score 14 or 15 were excluded because mostly they will achieve favorable outcome and also the number of patients with low admission GCS (4-8) was relatively small 22/93.These reasons reduced the impact of GCS on postoperative outcome.Concerning the EDH volume, our study was conducted only on large volume EDH (!40 cm 3 ) and there were no significant variations between included cases in regards to their EDH volume.
Statistical AnalysisTo tabulate and statistically analyze the results, SPSS V.22 (IBM Corporation, Armonk, New York, United States) and Microsoft Excel 2010 (Microsoft Corporation, Redmond, Washington, United States) were used.The descriptive statistics included mean (x) and standard deviation.The count data were expressed as the rate and analyzed using the chi-square test.Standard Student's t-test, for independent samples, was used for comparing the means between the two groups in various factors of the study.A pvalue of 0.05 was considered statistically significant.

Fig. 1
Fig. 1 Distribution of included patients among the different age groups.The highest percentage of patients (34.4%) were in the age group from 21 to 30 years, followed by 23.7% from 31 to 40 years and only 2.2% were > 50 years.No significant difference was found between the two groups in this regard.

Fig. 3 (
Fig. 3 (A, B) Adult patient presented 2 hours after road traffic accident with Glasgow Coma Scale (GCS) 8/15.(A) Initial computed tomography (CT) brain showing right temporoparietal large volume extradural hematoma (EDH) with midline shift.Patient underwent early surgical evacuation of EDH "within the first 6 hours after trauma."(B) Postoperative CT brain showing complete hematoma evacuation with improvement of midline shift.Postoperatively, GCS was improved to 14/15 and the patient had favorable clinical recovery at discharge.

Table 1
10e Extended Glasgow Outcome Scale (GOSE) score10 Can be left alone >8 hours during the day, but unable to travel and/or go shopping without assistance 3Sever disability (lower) Requires frequent help of someone to be around at home most of the time every day

Table 2
Preoperative general and clinical data of patients in the two study groups Abbreviations: F, female; GCS: Glasgow Coma Scale; INR, international normalized ratio; M, male; SD, standard deviation.Note: Group A: patients operated upon 6 hours after trauma; group B: patients operated upon >6 hours.Time to surgery: the time interval from head injury to the beginning of surgery in hours.a Statistically significant.

Table 3
Preoperative radiographic data of patients in the two study groups Abbreviations: EDH, extradural hematoma; L, left; MLS, midline shift; R, right.Note: Group (A): patients operated upon 6 hours after trauma; Group (B): patients operated upon > 6 hours.

Table 4
Postoperative results of patients in the two study groups Abbreviations: GOSE, Extended Glasgow Outcome scale; SD, standard deviation.Note: Group A: patients operated upon 6 hours after trauma; group B: patients operated upon >6 hours.Hospital stay: the length of stay "in days" in our department till discharge.Recovery after 1 month: was calculated after exclusion of the 8 cases who expired during the hospital stay.a Statistically significant.

Table 5
Predictors for postoperative functional recovery Abbreviations: EDH, extradural hematoma; F, female; GCS: Glasgow Coma Scale; M, male; MLS, midline shift; SD, standard deviation.Note: Time to surgery: the time from onset of trauma to the beginning of surgery.a Statistically significant.