With the rapid development of transportation industry, the incidence of traumatic spinal cord injury (SCI) is increasing year by year, and the incidence of traumatic SCI in the United States is 28-55 per million people, with about 10,000 new cases per year, and the incidence is highest in young patients [1, 2, 3, 4], and the prognosis of neurological function after acute SCI is still very unsatisfactory. Statistics in the United States show that the direct cost of SCI treatment throughout the United States in 1995 was as high as $7.7 billion [1, 2], and the actual situation in China may exceed that of the United States in terms of population proportion, although there are no exact relevant statistics. Acute SCI imposes a heavy economic and psychological burden on the whole society, families and individuals, and therefore the whole society is eager to cure SCI completely. numerous studies have shown that SCI can be divided into primary and secondary injuries according to the pathological evolution [1, 2, 5, 6]. Studies have shown that prevention and reversal of secondary SCI is important to maximize the preservation of residual spinal cord function and to promote structural and functional reconstruction of the injured spinal cord, and is one of the main means of treating SCI at present [1, 2, 5]. Currently, there is no specific drug that can effectively prevent and reverse secondary SCI and promote neurological recovery; therefore, surgical intervention is widely used in North America for the clinical treatment of acute SCI. However, due to the lack of rigorously designed and strictly executed randomized controlled clinical studies, there is still a great controversy among scholars regarding the definition of the time window for surgical treatment, the choice of surgical procedure, and the efficacy of surgery to promote neurological recovery [1, 2, 5, 7, 8, 9]. This paper presents a review of the research progress on the impact of the choice of surgical interventional treatment time on the prognosis of acute spinal cord injury. He Yongxiong, Department of Spine Surgery, People’s Hospital of Inner Mongolia Autonomous Region
1 The effect of the choice of the timing of surgical interventional treatment on the prognosis of acute spinal cord injury in animals
Studies have shown that time-responsive edema after SCI is a vasogenic edema caused by trauma resulting in loss of endothelial cell integrity and increased vascular permeability. Because the spinal cord dura is relatively fixed and not easily expandable, intramedullary edema spreads to the adjacent segments of the injury and is accompanied by increased intramedullary pressure. Twenty-four to 48 hours after severe SCI, there was necrosis at the site of injury, especially significant hemorrhage in the central gray matter region of the spinal cord. A few days later, a cavity forms in the hemorrhagic area, and there is diffuse necrosis in the cephalocaudal 2 cm of the spinal cord centered on the injury, usually with more distinct necrotic boundaries. This gradual evolution of cavity and necrosis formation in the injury area and in the adjacent parts of the injury is often accompanied by characteristic pathological changes such as infarction, the so-called post-traumatic infarction [6]. In contrast, alterations in spinal cord blood flow after SCI are an important cause of spinal cord necrosis and loss of neurological function, as well as of secondary spinal cord injury [6]. The injury is further aggravated by electrolyte disturbance, post-traumatic inflammatory response and apoptosis on the basis of spinal cord ischemia.Dimar et al [10] in 1999 strongly demonstrated experimentally that early spinal cord decompression can effectively alleviate and reverse secondary spinal cord injury. They replicated a rat model of thoracic spinal cord impact injury, followed by epidural placement of a compression device to cause continuous compression of the thoracic spinal cord, followed by decompression at 0, 2, 6, 24, and 72 hours post-injury. Shields et al [11] replicated a moderate spinal cord injury at the T10 level in rats and caused 38% and 43% spinal stenosis to simulate the stenosis caused by clinical spinal fracture dislocation. The results showed that rats that underwent early surgical decompression at 6 or 12 hours post-injury achieved better ability to support their body weight than those that delayed decompression until 24 hours post-injury. Zhang Qiang et al [12] further performed decompression surgery at 2 and 8 hours after injury in rats with 30% spinal stenosis caused by continuous compression after spinal cord injury at the T13 level. Postoperative pathomorphology showed that early surgical decompression after spinal cord injury had a protective effect on the spinal cord axons of the injured rats, reducing the area of spinal cord injury and promoting the recovery of hind limb function.
2 The effect of timing of surgical intervention on the prognosis of clinical acute spinal cord injury
Based on the above analysis, most scholars believe that the prognosis of neurological function of the body after acute SCI is closely related to the following three factors: 1) the degree of instantaneous primary injury; 2) the degree of spinal cord compression due to spinal fracture dislocation or hematoma; and 3) the duration of spinal cord compression [11]. In terms of current clinical treatment, there is a consensus that spine surgeons usually use interventional treatments for spinal cord decompression of the injured segment, repositioning of fracture dislocations, and stabilization and fusion of the spine for alleviating or relieving the latter two factors that contribute to spinal cord injury aggravation [5]. Although experimental animal studies have shown that early spinal cord decompression within hours after spinal cord injury can maximize neurological recovery by alleviating and reversing secondary spinal cord injury, there is still a great deal of controversy among spine surgeons on how to choose the optimal timing of interventional surgical treatment after SCI, focusing on the definition of the time window for early surgical treatment and whether early surgery increases the risk of SCI patients’ complications and lead to deterioration of neurological function [1, 2, 5, 7, 8, 9]. Some authors believe that surgical treatment within the 24-hour to 14-day time window after SCI is not sufficient to alter or reverse the course of secondary spinal cord injury, and that early emergency surgery increases the risk of surgery as SCI is often accompanied by multiple injuries throughout the body [7, 13].A multicenter prospective study conducted by Marshal [14] clearly does not support early interventional surgical treatment for acute SCI: in this study, four of the 26 patients who underwent surgery within 5 days of injury experienced deterioration in neurological function, whereas none of the 44 patients who underwent surgery after 5 days experienced deterioration in neurological function. The authors concluded that early surgery is not advisable especially for patients with cervical SCI. However, at the same time, 10 of the 149 patients awaiting surgery or receiving surgical treatment also experienced deterioration of neurological function, the incidence of which was close to that of patients receiving early surgical treatment. Therefore, Wang Yansong et al. analyzed Marshall’s study without sufficient data to illustrate the relationship between the choice of the timing of surgical treatment and the deterioration of neurological function [14]. In contrast, the deterioration of neurological function that occurs in conservatively treated patients is more likely to be due to instability of the spinal injury segment and has no clear relationship with the choice of the timing of surgery [14].
With further in-depth studies on the mechanism of secondary SCI, investigators proposed two golden windows of clinical treatment based on a nationwide randomized controlled clinical trial protocol for acute spinal cord injury: namely, high-dose methylprednisolone shock therapy given within 8 hours after acute SCI can achieve some efficacy, while high-dose methylprednisolone shock therapy given within 3 hours after injury can achieve better efficacy [1, 16]. These studies clearly suggest that the treatment of acute SCI should target the mechanism of secondary spinal cord injury, and the selection of the time window for interventional treatment is particularly important in the clinical treatment of acute SCI. In terms of clinical reality, the feasibility of interventional line surgery within 3-8 hours after acute SCI is low in most patients due to factors such as emergency care, resuscitation, transport, imaging and preparation before surgery after cervical spine trauma.Ng et al [15] in 1996-1997 treated 26 patients with traumatic C3-T1 spinal canal encroachment of 25% or more in eight spine surgery centers in North America within 8 hours after injury Decompression therapy was performed within 8 hours of injury: 1) traction alone; 2) traction plus surgery; and 3) surgery alone. The results showed that less than 10% of the patients meeting these criteria had cervical spine trauma at the eight spine surgery centers mentioned above during the same period, and only two patients were able to undergo surgical decompression within 8 hours of injury, while seven patients underwent surgical decompression within 12 hours of injury. The results of this prospective, non-randomized controlled study showed that early post-injury surgical decompression did not increase the incidence of surgery-related complications, and the authors concluded that delayed transport and imaging were the main reasons why most patients were not able to undergo surgical decompression within 8 hours and suggested that a new procedure should be reformulated so that more patients could be treated with surgical decompression within 8 hours of injury.Pointillart et al [17] in another prospective, non-randomized controlled study investigating 49 patients with SCI undergoing surgical decompression fixation within 8 hours post-injury. The authors found that patients operated within 8 hours after injury did not recover better neurological function than those operated within 8-24 hours after injury or without surgery, concluding that the prognosis for neurological function after SCI is primarily related to the degree of initial spinal cord injury. However, the authors did not elucidate the number of patients who completed surgical decompression within 8 hours, and also the small number of patients enrolled in the surgical group may have been an important factor in the determination of efficacy. in a prospective, non-randomized controlled study of 91 patients with cervical spinal cord injury, Papadopoulos [7] et al. found that 34 patients who underwent emergency surgical decompression within 12.6 hours after injury guided by emergency MRI The patients recovered satisfactorily from neurological function with no significant emergency surgical complications. The authors counted 39 satisfactory neurological recoveries among the 66 patients who underwent surgery overall (including some with full SCI), whereas only 6 of the 25 patients in the non-surgical group had neurological improvement, but the authors did not compare the difference in neurological recovery between patients who underwent surgical decompression within 12.6 hours of emergency and those who underwent surgical decompression after that time, possibly related to the small number of patients in this group.
To establish the feasibility of determining the relationship between the choice of timing of surgical decompression and neurological recovery after SCI through a standard large-scale randomized controlled, prospective clinical study, Tator et al [18] conducted a retrospective clinical survey: the authors’ retrospective clinical case data were obtained from 36 spine surgery centers in North America, with 585 patients meeting the inclusion criteria between 1994 and 1995, and this represented only 50% of similar patients admitted to these centers during the same period, and the other 50% were not enrolled because of late admission, age, open injuries, and lack of spinal cord compression. Of these patients, 65% underwent surgical decompression: 23.5% operated within 24 hours of injury; 15.8% operated 25-48 hours after injury; 19% operated 48-96 hours after injury; and 41.7% of patients operated after 5 days. The authors concluded that there is no clear evidence that the surgical treatment described above promotes neurological recovery, and there is considerable controversy over whether early surgery reduces the length of hospital stay and the occurrence of complications such as pneumonia and deep vein thrombosis. Although surgical decompression is more commonly used by physicians in North America to treat acute spinal cord injuries, there is no consensus among clinical treatment centers on the choice of the point of post-injury interventional surgical treatment. Judging from the statistical data that only a very small number of patients receive surgical treatment within 24 hours, the authors concluded that if large randomized controlled, prospective clinical studies are needed to determine the optimal time window for post-injury treatment, more extensive public education on field first aid and specific training for emergency department physicians are necessary to allow more patients to be brought to the hospital for treatment within the shortest possible time after injury Based on these findings, Rosa et al [19] further defined spinal cord decompression surgery within 24 hours of injury as an early surgical treatment group, and surgery beyond 24 hours as a late surgical treatment group. The authors retrospectively reviewed the clinical research literature published from 1996-2000 and analyzed the clinical data of 1687 patients who underwent early surgical decompression, late surgical decompression, and non-surgical treatment, respectively, showing that early interventional surgical decompression, repositioning, and stabilization of the spine within 24 hours after acute SCI was consistent, at least in terms of safety, with delayed surgery after 24 hours post-injury, but that patients who received Patients treated with acute surgery within 24 hours had a higher neurological recovery. However, the authors further concluded by analysis of homogeneity that only patients with incomplete SCI who underwent early surgical decompression achieved better clinical outcomes (89.7%). The authors acknowledged that early surgical decompression for acute spinal cord injury is a practical treatment option, but numerous different variables have been found in clinical case studies to influence the final outcome of neurological recovery; therefore, a prospective, randomized controlled clinical study as soon as possible is the best way to determine the time point for interventional surgical decompression. For example, in a study by Tuil et al [20], it was found that a higher percentage of patients with an ASIA-graded cervical SCI up to grade A with concurrent hypotension and bradycardia received surgical decompression treatment at a mean of 80.9 hours post-injury, whereas patients with the same level of injury without concurrent hypotension and bradycardia received surgery at a mean of 58 hours. These variables are all factors that influence the determination of the time to surgery and can likewise have an impact on the prognosis of neurological function.
Most clinical investigators have limited the time to early surgical decompression to within 72 hours after injury and late surgery to beyond 72 hours after injury based on the above mentioned reasons.Mirza et al [21] retrospectively reported that 15 of 30 patients with cervical SCI underwent surgical decompression within 3 days after injury and the remaining 15 underwent surgical decompression after 3 days. The authors observed that early surgical treatment within 3 days promoted recovery of neurological function and did not increase the incidence of complications, while shortening the length of hospital stay. In contrast, Sapkas et al [22] retrospectively analyzed the data of a group of 31 patients who underwent surgical decompression and fixation within 72 hours of injury and 36 patients who underwent surgical treatment after 72 hours of injury, and they concluded that there was no difference in the overall neurological prognosis between early and late surgical treatment. Only patients with an initial incomplete cervical spinal cord injury have the potential for postoperative neurological recovery, and early surgery may be more beneficial for patients with incomplete spinal cord injuries. In addition, early surgery for cervical SCI is safe and does not demonstrate postoperative neurological deterioration. The authors acknowledge that defining 72 hours post-injury as early may in fact not be the optimal time window for early interventional surgical treatment and that further prospective randomized controlled studies are needed. The data show that a clinical study by Vaccaro et al [13] on the prognostic impact of early or late surgical decompression on neurological function in a group of patients with cervical SCI is the only prospective, randomized controlled study available. The authors treated 34 patients with early surgical decompression within 72 hours of injury and 38 patients with surgery 5 days after injury, and the results of their clinical data showed no difference in neurological recovery or length of hospital stay between the early and late surgical treatment groups. However, it is worth noting that a total of 20 patients in this group were lost to follow-up, so its conclusion needs further clinical investigation and study. Numerous domestic scholars [14,23,24] have also done a series of useful studies on the correlation between the timing of surgical interventions and the prognosis of neurological function after acute cervical spinal cord injury, and it is generally believed that surgical interventions for acute cervical SCI should be performed as early as possible within 3 days after injury in the hope of obtaining better neurological recovery.
Duh et al [25] investigated the neurological recovery of patients with early (within 25 hours) and late (more than 200 hours) surgery and conservative treatment after SCI by post-hoc analysis of clinical data from the Second National SCI Treatment Study, and concluded that both early and late surgery promoted neurological recovery, with no significant difference. The authors analyzed that the surgical time window of 25 hours and more than 200 hours after injury may have avoided the post-traumatic spinal cord edema period, thus avoiding the deterioration of neurological function due to surgery. It is worth noting that this clinical study was a randomized, double-blind controlled study of the efficacy of two drugs for spinal cord injury, so the selection of patients for surgery time did not allow for randomized grouping, and the authors are aware that the conclusions of this study require further clinical prospective, randomized controlled studies.
3 Impact of the choice of surgical interventional treatment time on complications and length of stay in patients with clinical acute spinal cord injury
Because SCI, especially high-grade cervical SCI, is often associated with cardiopulmonary impairment, some scholars believe that early surgical treatment may increase the complications of spinal cord injury in these patients and make surgery extremely risky, which is one of the controversial points affecting the choice of the timing of surgical intervention. However, with the rapid improvement in the modern level of spinal surgery technology and surgeon’s self-confidence, intensive care and neuroanesthesia, there has been little difference in the surgical complications associated with early surgery for acute spinal cord injury and non-surgical treatment [1].Duh et al [25] showed that surgery within 24 hours after injury had a lower complication rate than late surgery.Schlegel et al [26], on the other hand, found that Schlegel et al [26] found higher complications of pulmonary and urinary tract infections in patients treated surgically 3 days after injury, while Fehlings et al [1] found a mild increase in the incidence of deep vein thrombosis in the surgically treated group compared to the non-surgical group.Waters et al [27] conducted a prospective study of 2204 patients with spinal cord injury and found no difference in complication rates between the surgical and non-surgical treatment groups. The results of the prospective, randomized controlled clinical data of Vaccaro et al [13] showed no difference in neurological recovery and length of hospital stay between the early and late surgical treatment groups, which is consistent with the findings of clinical studies by Mirza [21] and Chen [28], among others.Mckinley et al [9] concluded that although early surgery within 72 hours after injury does not promote better neurological recovery, it shortens the length of hospital stay. better recovery, it can shorten the length of hospital stay and reduce respiratory complications such as pneumonia and atelectasis. Therefore, most of the current literature suggests that surgery within 3 days after injury is safe for spinal cord injury.
4 Problems with clinical studies
Fehlings et al [1, 2] classified the results of clinical type studies into 3 categories: category I are clinical randomized controlled trial studies with well-designed study protocols that can be strictly executed; category II are prospective non-randomized controlled studies; and category III are retrospective studies or case reports and expert reviews. It is clear that the results of Class I clinical studies are the most convincing, and Fehlings et al [1, 2] recently did a systematic review of the published literature on the effects of decompression on neurological recovery after SCI over the last 10 years, and especially over the last 5 years. It was found that out of all 66 publications, none of them were Class I clinical studies, all of them were Class II and III clinical studies. And among them, only one literature could do randomized controlled grouping study [13], and the rest of clinical studies could not do randomized controlled grouping. Fehlings et al [1, 2] concluded that the relationship between the timing of acute SCI surgical decompression on the prognosis of neurological recovery is inconclusive based on the current state of clinical research. To address this clinical dilemma, his research center at the University of Toronto, in conjunction with several other spine institutes, initiated a multicenter (a single research unit does not have sufficient clinical cases to further subdivide patients into more subgroups for controlled studies [25]), prospective clinical trial study to evaluate the effects of surgical decompression within 24 hours (early) and after 24 hours (late) after acute spinal cord injury on cervical function. late) surgical decompression on the prognostic impact of cervical SCI. This study requires good collaboration between spinal surgeons and imaging physicians and a high level of emergency critical care, which the authors believe is available in the multicenter study described above. However, the authors analyzed the randomized controlled grouping of patients in this study due to a number of factors such as ethics and technicalities that limited the study. For example, the ethics are such that physicians would not assign a patient with deteriorating neurological function to the late surgical group in clinical care; and the technicalities of emergency care and imaging limit the number of patients who can arrive at the spine surgery center to be treated within 24 hours. in their study, Mckinley et al [9] noted the following characteristics in the composition of the early surgical group within 72 hours: mostly high-energy car accident injuries and a high prevalence of female patients. The authors concluded that high-energy crash injuries, unlike fall injuries and medically induced spinal cord injuries, are associated with vertebral fractures and instability and therefore require early surgery. Patients who underwent surgery after 72 hours post-injury had incomplete spinal cord injuries. These clinical study data reflect the difficulty of randomized grouping in clinical treatment from one side. Therefore, the authors suggest that the lack of difference in neurological recovery between the early and late surgical and non-surgical treatment groups in this study may be due to the different neurological status of the patients at the time of initial grouping.
5 Conclusion
Although numerous animal studies have shown that early surgical decompression after spinal cord injury can alleviate and reverse secondary spinal cord injury, there is still no clinical consensus on whether there is a similar window of treatment for surgical decompression as in animal studies. In other words, clinicians have not yet reached a uniform understanding of the role of surgery in the treatment of acute SCI and the timing of surgery. From the data of a large number of Class II clinical studies, the initially formulated guidelines are that early surgical decompression within 72 hours is safe and effective in hemodynamically stable patients [1, 2], and acute surgical decompression should be recommended for patients with progressive deterioration of neurological function after SCI. And from a large number of Class III clinical study data, the preliminary proposed alternative is [1, 2]: surgical decompression for acute cervical SCI is a practical treatment, as long as the patient does not have life-threatening multisystem trauma, and surgical decompression within 24 hours after the injury as much as possible, which also reduces the incidence of post-traumatic complications and shortens the length of hospital stay. In conclusion, for SCI, a difficult-to-treat worldwide medical problem, a global multicenter systematic collaborative large sample clinical case analysis discussion is one of the ways to solve this problem.