In this study, we explored the safety and efficacy of thrombolysis in the process of transport and treatment by comparing the two transport methods of DS and non-DS. In the non-DS group, most patients did not receive thrombolysis because the thrombolytic time window had passed, so the OTP was significantly longer in these patients than in the DS group (non-DS median, 463 minutes; IQR, 335–787 minutes versus DS median, 94 minutes; IQR, 82–116 minutes; P < 0.001). After the patients in the DS group were admitted to the PSC, the process of IVT and observation after thrombolysis prolonged the time patients received endovascular therapy, resulting in a longer PTG in the DS group than in the non-DS group (DS median, 271 minutes; IQR, 204–364 minutes versus non-DS median, 162 minutes; IQR, 111–240 minutes; P = 0.002). The above two points combined may be the reason no statistical difference in OGT was observed between the two groups, although a trend for OGT in the non-DS group to be longer than that in the DS group was present (non-DS median, 441.5 minutes; IQR, 398.5-635.25 minutes versus DS median, 390 minutes; IQR, 326–500 minutes; P = 0.807). There was also no significant difference in prognosis between the DS and non-DS groups. Currently, most PSCs cannot perform multimodal CT evaluation. Patients who meet the conditions for thrombolysis, are transferred to the CSC for imaging evaluation and MT after receiving IVT. Transport did not appear to increase the risk of post-thrombolytic cerebral hemorrhage, postoperative malignant cerebral edema, or death, as all groups were similar for these outcomes.
Previous retrospective studies show that patients in the MS group present a higher chance of functional independence[7–9]. Adams et al.[10] provide an exception, having found similar outcomes after thrombectomy in the MS and DS groups. According to our data, the DS group had a longer OGT than the MS group (DS median, 390 minutes; IQR, 326–500 minutes versus MS median, 235 minutes; IQR, 159–270 minutes; P < 0.001), but this did not coincide with any significant difference in the rates of hemorrhagic transformation, malignant cerebral edema, or 90-day mortality. Studies have shown that the most important factor for obtaining good functional outcomes is rapid cerebral reperfusion and the shorter the OGT, the better the prognosis[11]. In our study, the OGT in the DS group was longer, but the thrombectomy effect was enhanced without increasing the complication rate; this may reflect benefits of thrombolysis before transport. In comparison, the DS group had shorter OTN than the MS group (111.7 ± 47.7 versus 150.9 ± 48.8, P = 0.041), which we attribute to the smaller scope of services offered by PSCs and smooth traffic in remote areas. In addition, patients in the DS group received IVT earlier than the MS group, which is also an important factor in patient prognosis. Finally, although the two groups did not significantly differ in DPT, the DS group tended to have a shorter DPT than the MS group (110.6 ± 35.1 versus 124.9 ± 42.5, P = 0.346). The early warning by the PSC before transfer may lead to the shorter DPT in the DS group and in timely treatment of patients transferred to CSC; this is consistent with results of previous studies[12, 13].
Early IVT can be more effective for distal vascular occlusion caused by small thrombi than for LVO[14]. A meta-analysis of 13 studies showed that only 11% of patients with LVO who received IVT achieved recanalization[15]. In our data, all patients in the DS group achieved successful recanalization, whereas two patients in the non-DS group and three patients in the MS group did not. In addition, 17 patients with no LVO detected by multimodal CT after transport to our hospital may have benefitted from thrombolysis before transport. After completion of the cerebrovascular imaging examination in the CSC, only two patients in the DS group had an ischemic core volume exceeding 70 ml. Since the PSC did not complete the cerebral vascular imaging evaluation, we cannot obtain an accurate measure of cerebral perfusion before transfer; we are thus unable to assess the effect of thrombolytic therapy in patients prior to transport. Since thrombolysis has limitation on the recanalization of LVO, we speculate while thrombolysis likely failed to achieve the recanalization of vessels in patients with LVO in the DS group, it may have led to the establishment of collateral circulation[16]. This response delays the progression of the ischemic core without increasing the probability of hemorrhagic transformation, and is thus beneficial for brain tissue reperfusion and postoperative neurological recovery.
With the publication of the DAWN and DEFUSE-3 studies, imaging-based physiological information may shift the treatment paradigm from a rigid time-based model to a more flexible and individualized, issue-based approach, increasing the proportion of patients considered appropriate for treatment. Multimodal CT includes NCCT, CTA, and CTP. It can achieve rapid and accurate assessment of LVO, collateral circulation, volume of ischemic penumbra and volume of ischemic core[17]. However, in China and other developing countries, most PSCs can only preliminarily assess patients using NCCT to assess whether bleeding lesions and severe cerebral infarction are present; such facilities cannot assess the presence of LVO and abnormal cerebral perfusion accurately. The first multimodal CT assessment can only be completed after transported to the CSC. NCCT is widely used in the evaluation of neurocritical care as it has the benefits of being fast and effective. It can provide information for the identification of hemorrhage and ischemic lesions quickly, but it has limitations in detection of early ischemic lesions[18]. The Alberta Stroke Programme Early CT (ASPECT) score is an important method to quantify early ischemic changes based on NCCT imaging, and it is widely used in clinical practice for its simplicity and effectiveness. However, clinical decisions can differ from one clinician to the other[19]. In addition, the prediction of the prognosis of AIS patients based on the ASPECT score is controversial. The results of the MR CLEAN study showed that a higher ASPECT score predicts good prognosis of patients[20]. However, the SWIFT PRIME and ESCAPE studies found no significant difference in prognosis, intracranial hemorrhage and mortality between patients with ASPECT scores 4–6 and those with ASPECT scores 7–10[21, 22]. Insensitivity to the diagnosis of early ischemic lesions limits the role of NCCT in thrombectomy decision-making. In the present study, multimodal CT assisted us to screen patients who were transferred from a PSC to our hospital. A total of 28 patients without LVO or with large volume of ischemic core were excluded from our study. Among the enrolled patients, multimodal CT also helped us to identify the location of the LVO, the status of collateral circulation and the perfusion of brain tissue, and provided guidance and help for MT methods. If PSCs are able to perform multimodal CT evaluation, the vascular occlusion and cerebral tissue perfusion can be evaluated and screened at the first visit of the patient, thereby reducing the potential safety hazards caused by unnecessary transport, improving economic benefits, and achieving more precise treatment.
According to map data calculations, the distance from the PSCs to our hospital is 55 kilometers, and the estimated transit time is 60 minutes, but the actual transit time is greatly prolonged, resulting in the median OGT time of the DS group being 155 minutes longer than that of the MS group and leading to delayed recanalization in DS patients. There are two reasons for this delay. First, the patients did not start the referral system immediately after IVT in the PSC but instead continued to be observed during IVT. The referral program was only started when it was determined that the thrombolysis was ineffective or if patient conditioned worsened after thrombolysis. This increased the time patients received endovascular therapy. Second, after the doctor and patient made the decision to transfer to the CSC for evaluation, waiting for the ambulance to arrive delayed the patient's transfer. Another study found that MS patients have a higher chance of functional independence, especially when the distance between the PSC and the CSC is > 12.5 miles or when the time between cerebral imaging and groin puncture is ≥ 140 minutes[12]. There was no statistically significant difference in the prognosis between DS and MS patients in our study, although the proportion of patients in the MS group who achieved functional independence did tend to be higher (7/17 or 41.2% versus 4/12 or 33.3%), consistent with the above findings. Therefore, optimizing the admission and treatment process of the PSC is necessary for AIS. Once IVT is given, the transport mechanism to CSC should be activated immediately to accelerate the cerebral reperfusion and improve the prognosis of patients.
In conclusion, the DS method is safe and effective, with no increased risk of postoperative hemorrhage transformation, malignant edema or death compared to non-DS and MS methods. A limitation of our study is the small size sample and that it included cases in the past year only. In future, we will include more cooperative medical institutions, and prospectively collect a larger sample to verify conclusions. Another limitation is the restrictions of equipment in PSCs. AIS patients cannot receive multimodal CT in the PSC, and thus we cannot ascertain whether thrombolysis achieves recanalization of occluded vessels, or whether the thrombus dissolves and migrates.