Brain metabolism response to intrahospital transfers in neurocritical ill patients: Does the microdialysis probe location matter?

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Leire Pedrosa, John Hoyos, Luis Reyes, Alejandra Mosteiro, Luigi Zattera, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3180261/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 28 Mar, 2024 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Intrahospital transfer (IHT), a routine in the management of neurocritical patients requiring imaging or interventions, might affect brain metabolism. Studies about IHT effects using microdialysis (MD) have produced conflicting results. In these studies, only the most damaged hemisphere was monitored, and those may not reflect the impact of IHT on overall brain metabolism, nor do they address differences between the hemispheres. Herein we aimed to quantify the effect of IHT on brain metabolism by monitoring both hemispheres with bilateral MD. In this study, 31 patients were included, with a total of 73 IHT. Glucose, glycerol, pyruvate and lactate were measured by MD in both hemispheres for 10 hours pre- and post-IHT. Alterations in metabolite levels after IHT were observed on both hemispheres; although these changes were more marked in hemisphere A (most damaged) than B (less damaged). Changes in metabolite levels in hemisphere B were more evident in cerebrovascular than in traumatic brain injury patients. Our results suggest that, brain metabolism is altered after an IHT of neurocritical ill patients, particularly but not limited to the damaged hemisphere. Bilateral monitorization may be more sensitive than unilateral monitorization for detecting metabolic disturbances not directly related to the course of the disease. Biological sciences/Neuroscience Health sciences/Biomarkers Health sciences/Medical research Health sciences/Neurology microdialysis monitoring brain metabolism intrahospital transfer neurocritical patients traumatic brain injury neurovascular disease Figures Figure 1 Figure 2 Figure 3 Introduction Intrahospital transfer (IHT) is a routine process in intensive care units (ICU) for neurocritical patients 1 . Actually, at least two IHTs are needed when an advanced imaging study or surgical or interventional treatments are deemed necessary. Most centers try to minimize the number of IHTs of neurocritical patients, as they may result in airway management problems, medication disruption, positional changes, and ventricular drainage discontinuation 2,3–5 . These situations experienced during IHTs may cause an increase in intracranial pressure (ICP) and/or brain hypoxia leading to secondary brain injury (SBI), thus worsening the clinical outcome. Metabolic dysregulations may reflect this iatrogenic SBI and therefore cerebral microdialysis (MD) monitoring has been one of the tools used to investigate the consequences of IHT in neurocritical patients. However, the results obtained so far are diverse and contradictory, ranging from the absence of metabolite changes during or after IHT to increases in glycerol, lactate and pyruvate levels immediately after IHT 6 . In these previous studies, the MD monitorization was conducted unilaterally, specifically in the hemisphere defined as the one most damaged. Nevertheless, the difficulty in defining the hemisphere at higher risk is well known 7–10 and relevant information may be overlooked when only one hemisphere is monitored 11 . The purpose of our study is to quantify the effect of IHT on brain metabolism of neurocritical patients monitored with bilateral MD probes and to assess the differential impact of the underlying pathology on the presence of bilateral brain metabolism. Results Overall, 76 IHT from 33 patients were collected. Three IHT corresponding to two patients who died within 24 hours of IHT were excluded from the final analysis. Of the remaining 73 IHT analyzed, the mean transfer time was 21 ± 6 minutes. A total of 89% (65/73) of IHT were done to obtain a CT, 9.6% (7/73) to acquire an angiography, and 1.4% (1/73) to perform an endovascular treatment (Fig. 1 ). Patient characteristics and transfers Out of the 31 patients analyzed, 17 (17/31; 55%) were male. The mean age was 48 years (range 20–72) and the mean GCS at admission was 7 (range 3–14). Most of the patients (20/31; 69%) were admitted in coma (GCS ≤ 8). The cause of the brain injury was vascular pathology in 21/31 cases (68%) and TBI in 10/31 (32%). Out of the 31 patients, 16 (52%) required surgical intervention, 5 (16%) required a surgical evacuation of an intraparenchymal hematoma, 3 (10%) underwent a decompressive craniectomy, 4 (13%) needed a craniotomy for aneurysm clipping, and 3 (10%) more required aneurysms clipping plus hematoma drainage (Table 1 ). A good clinical outcome was observed in 32% (9/28) of the patients at hospital discharge and in 76% (16/21) at 3 months follow-up. Table 1 Demographic and Clinical variables of the patients included in the study. Data are first described in the global group and then categorized according to the pathological admission diagnosis (vascular or traumatic brain injury). TBI: Traumatic brain injury, GCS: Glasgow Coma Scale (GCS), mRS: modified Rankin Scale score, IHT: Intrahospital transfer, DCI: Delayed cerebral ischemia. The table shows the p-value obtained by comparing the subjects in each variable in each pathological group with the chi-square test. Total (n = 31) Vascular (n = 21) TBI (n = 10) p-value n (%) n (%) n (%) Sex Male 17 (54.83%) 9 (42.90%) 8 (80.00%) 0.052 Age Mean (min-max) 48 (20–72) 54 (37–72) 32 (20–61) < 0.001 GCS at hospital admission Severe (3–8) 20 (68.97%) 12 (63.16%) 8 (80.00%) 0.64 Moderate (9–12) 5 (17.24%) 4 (21.05%) 1 (10.00%) Good (13–15) 4 (13.79%) 3 (15.79%) 1 (10.00%) Surgery Non-surgery 16 (51.61%) 10 (47.61%) 6 (60.00%) Hematoma drainage 5 (16.13%) 4 (19.05%) 1 (10.00%) Aneurysm clipping plus hematoma drainage 3 (9.68%) 3 (14.29%) 0 (0.00%) Decompressive craniectomy 3 (9.68%) 0 (0.00%) 3 (30.00%) Aneurysm clipping 4 (12.9%) 4 (19.05%) 0 (0.00%) DCI Non-DCI 7 (70.00%) 7 (70.00%) 0 (0.00%) Clinical 1 (10.00%) 1 (10.00%) 0 (0.00%) Radiological 2 (20.00%) 2 (20.00%) 0 (0.00%) Number of IHT 1 9 (29.03%) 6 (28.57%) 3 (30.00%) 0.249 2 10 (32.26%) 5 (23.81%) 5 (50.00%) 3 or more 12 (38.71%) 10 (47.62%) 2 (20.00%) Status on the day of discharge Bad 19 (67.86%) 16 (84.21%) 3 (33.33%) 0.007 Good 9 (32.14%) 3 (15.79%) 6 (66.67%) Outcome at 3 months Bad 5 (23.81%) 4 (28.57%) 1 (14.29%) 0.46 Good 16 (76.19%) 10 (71.43%) 6 (85.71%) Most of the patients (12/31; 3%) underwent 3 or more transfers, 10 (10/31; 32%) patients had 2 transfers, and 9 patients (9/31; 29%) had only one transfer. Those patients who required a higher number of transfers were predominantly cerebrovascular cases (10 SAH vs. 2 TBI patients). The most frequent number of transfers in TBI patients was 2 (5/10; 50%), whereas most vascular patients (10/21; 48%) required 3 or more transfers (Table 1 ). Brain Metabolism Before IHT, the levels of glycerol were higher on side A than on side B (mean 300 vs 244 µmol/l, p 0.05). After IHT, our data showed a decrease in glucose (1.95 mmol/l pre-IHT vs 1.72 mmol/l post-IHT, p < 0.0001), an increase in glycerol (300 µmol/l pre-IHT vs 392 µmol/l post-IHT, p = 0.001) and an increase in LPR (35 pre-IHT vs 43 post-IHT, p = 0.005) on side A , in comparison with side B . Similarly, we also observed a decrease in glucose (1.90 mmol/l pre-IHT vs 1.70 mmol/l post-IHT, p = 0.011), and a significant increase in glycerol (245 µmol/l pre-IHT vs 272 µmol/l post-IHT, p = 0.005) on side B . In contrast to side A , on side B no statistically significant differences in LPR were observed (33 pre-IHT vs 32 post-IHT, p = 0.658) (Fig. 2 and Table 2 ). In addition, a statistically significant increase in lactate was observed on side A , while this difference was absent on side B . Table 2 Metabolites analyzed by MD in both hemispheres pre- and post-IHT. Mean concentration of each metabolite and SD from affected (A side) and non-affected (B side) hemispheres were shown. The p-value was obtained by comparing the values pre and post-IHT with the t-test Student. IHT: Intrahospital transfer, LPR: Lactate/pyruvate ratio. A side B side Pre IHT Post IHT p-value Pre IHT Post IHT p-value Glucose (mmol/L) ± SD 1.95 ± 0.921 1.72 ± 0.915 P < 0.0001 1.90 ± 1.398 1.70 ± 1.168 0.011 Glycerol (Umol/L) ± SD 300.27 ± 303.7 391.83 ± 321.8 0.001 244.69 ± 208.25 272.30 ± 190.775 0.005 Pyruvate (Umol/L) ± SD 126.61 ± 68.90 133.99 ± 64.47 0.007 109.49 ± 56.38 116.18 ± 55.43 0.003 Lactate (mmol/L) ± SD 4.16 ± 3.04 4.95 ± 3.376 P < 0.0001 3.78 ± 3.089 3.77 ± 2.691 0.066 Pyruvate (Umol/L) ± SD 126.61 ± 68.90 133.99 ± 64.47 0.007 109.49 ± 56.38 116.18 ± 55.43 0.003 LPR ± SD 35.01 ± 27.85 42.57 ± 46.42 0.005 33.06 ± 17.22 31.89 ± 13.14 0.658 Regarding the results obtained in the most affected side ( side A ) according to the underlying pathology (vascular vs TBI), we found a decreased level of glucose before and after IHT in both pathologies: TBI patients (1.89 mmol/l pre-IHT vs 1.62 mmol/l post-IHT, p = 0.016) and vascular patients (1.98 mmol/l pre-IHT vs 1.77 mmol/l post-IHT, p = 0.002). Besides, there was also an increase in LPR in TBI patients (28 pre-IHT vs 36 post-IHT, p = 0.055) and in the vascular pathology group (38 pre-IHT vs 45 post-IHT, p = 0.028) (Fig. 3 and Table 3 ). Table 3 Metabolites analyzed by MD in both hemispheres pre- and post-IHT. Mean concentration of each metabolite and SD from affected (A side) and non-affected (B side) hemispheres were shown. Patients were grouped according to the pathological diagnosis (vascular and traumatic brain injury). The p-value was obtained by comparing the values pre- and post-IHT with the t-test Student. TBI: Traumatic brain injury, IHT: Intrahospital transfer, LPR: Lactate/pyruvate ratio. A side B side Metabolite Pathology Pre IHT Post IHT p-value Pre IHT Post IHT p-value Glucose (mmol/L) ± SD TBI 1.888 ± 1.048 1.624 ± 0.9814 0.016 2.069 ± 0.9855 2.099 ± 1.427 0.225 Vascular 1.982 ± 0.870 1.766 ± 0.8870 0.002 1.847 ± 1.515 1.553 ± 1.021 0.017 Glycerol (Umol/L) ± SD TBI 300.9 ± 380.2 376.0 ± 400.3 0.012 219.1 ± 266.7 244.8 ± 219.5 0.059 Vascular 300.0 ± 271.2 346.3 ± 288.1 0.016 254.2 ± 181.9 282.5 ± 178.2 0.025 Lactate (mmol/L) ± SD TBI 3.470 ± 3.642 4.305 ± 3.904 0.001 2.366 ± 1.651 2.378 ± 1.109 0.059 Vascular 4.421 ± 2.748 5.186 ± 3.132 0 4.311 ± 3.308 4.292 ± 2.897 0.242 Pyruvate (Umol/L) ± SD TBI 116.8 ± 79.73 123.2 ± 81.02 0.185 92.25 ± 44.06 91.77 ± 31.08 0.255 Vascular 130.3 ± 64.19 138.0 ± 56.86 0.1 115.9 ± 58.90 125.2 ± 59.33 0.004 LPR ± SD TBI 27.75 ± 12.94 35.73 ± 23.00 0.055 25.20 ± 9.927 27.83 ± 9.064 0.253 Vascular 37.71 ± 31.09 45.11 ± 52.10 0.028 35.98 ± 18.33 33.41 ± 14.02 0.243 Meanwhile, in side B , a number of differences were observed between pre- and post-IHT periods in the vascular pathology group including increases in glycerol levels (254 µmol/l pre-IHT vs 283 µmol/l post-IHT, p = 0.025) and pyruvate levels (116 µmol/l pre-IHT vs 125 µmol/l post-IHT, p = 0.004), and decreases in glucose levels (1.85 mmol/l pre-IHT vs. 1.55 mmol/l post-IHT, p = 0.017). Conversely, no statistically significant differences were found in the LPR (36 pre-IHT vs 33 post-IHT, p = 0.243) nor in lactate levels (4.31 mmol/l pre-IHT vs 4.29 mmol/l post-IHT, p = 0.242). Interestingly, in vascular patients, the LPR on side B did not change after the transfer, as compared to the increase observed on side A . In the TBI group, no differences were seen in the metabolic parameters on side B before and after IHT (Fig. 3 and Table 3 ). Discussion The clinical repercussions of IHT in neurocritical patients have been debated over the last years 1,2 , with some authors advocating keeping the patient in ICU as much as possible thus reducing transfer outside the unit. However, balancing the potential risk and benefits of IHT is not an easy task. On one hand, diagnostic tests and therapeutic interventions requiring an IHT may be lifesaving. On the other hand, the metabolic response of the brain to IHT may cause SBI thus hindering the odds of patient recovery. However, the brain response to IHT is not well understood, especially regarding the less-affected hemisphere, which is usually not monitored. Furthermore, data on whether this response may vary depending on the underlying pathology is also lacking. In this scenario, the present study aimed to assess the impact of IHT on brain metabolism in neurocritical patients through the use of bilateral MD monitoring. Interestingly, our results suggest that IHT affects the brain metabolism not only in the hemisphere with more damage (side A), but it also on the side with less initial injury (side B). Moreover, we observed that this side B impairment seems to vary according to the underlying pathology. Therefore, this “contralateral” response to IHT might be significant in the patient’s overall prognosis and could be of greater importance in pathologies with more diffuse damage. Our findings revealed significant effects of IHT on cerebral metabolism, particularly on the more damaged side (A). Specifically, on side A we observed after IHT a notable increase in glycerol levels, a significant decrease in glucose levels, and a significant increase in the LPR. These changes may be attributed to episodes of hypermetabolism or “metabolic crises”, which have been linked to unfavorable outcomes 12–14 . The stress induced by IHT could be responsible for the observed decrease in glucose levels though the enhancement of anaerobic glycolysis and eventually resulting in an elevated LPR 15 . Importantly, an elevated LPR has been associated with the development of delayed cerebral ischemia (DCI) in subarachnoid hemorrhage (SAH) patients, suggesting that IHT may increase the risk of DCI following transfers 16 . In previous studies 6,8–10,17,18 , similar results were obtained regarding the increase in glycerol after IHT. However, in contrast with our observed data some of these studies did not find variations in other parameters of brain metabolism. Küchler et al. found no difference in metabolite levels before and after IHT in intracranial hemorrhage (ICH), subarachnoid hemorrhage (SAH) and brain trauma. The study concluded that although most of the metabolites analyzed increased after IHT, these changes were not related to incident metabolic crisis 18 . Contrarily and in line with our results, Hosman et al. found significant increases in difference glycerol, lactate and pyruvate levels after IHT, suggesting that IHT affects the brain metabolism of neurocritical patients 6 . The main novelty provided by our investigation was the assessment of the effects of IHT on cerebral metabolism in patients monitored with bilateral MD. Similar to the metabolite changes found on side A, we also observed on side B a significant increase in post-transfer glycerol levels, indicating acute neuronal damage. However, while glucose levels decreased significantly after transfer, no significant changes in the LPR were observed. This suggests that side B did not experience the same level of stress-induced anaerobic glycolysis as that observed on side A. Furthermore, analyzing metabolism disturbances by pathology, we observed that TBI patients presented a significant decrease in glucose, an increase in glycerol and an increase in lactate (without a significant increase in the LPR) only on side A. Meanwhile, on side B , no significant differences were observed in these values. Conversely, in the vascular pathology group, several metabolite changes were noted. On side A we found a significant decrease in glucose levels, an increase in glycerol, in lactate and in the LPR, while on side B a significant increase in glucose, glycerol and pyruvate levels was observed. These results suggest that side B in vascular pathology is more prone to local metabolic disturbances than side B in TBI. Presumably, in TBI the brain damage is more local than in cerebrovascular pathology, and the contralateral hemisphere maintains a certain capacity to autoregulate under stress conditions. Contrarily, in SAH patients the dysregulation seems to be more global, putting both hemispheres at risk of developing secondary damage. Therefore, our findings suggest that some neurocritical patients may benefit more from bilateral monitoring than others. Arguably, in patients affected by pathologies of vascular origin such as SAH, bilateral monitoring may help for enhancing the detection of ischemic events. Conclusions Our results suggest that IHT may lead to disturbances in the brain metabolism of neurocritical ill patients, as evidenced by the changes observed in MD registries. The metabolic alterations seemed to be more pronounced on the hemisphere with more primary damage than in the contralateral one, particularly in patients with TBI. However, it is important to note that IHT may also cause some degree of impairment, albeit less severe, on the contralateral hemisphere, especially in patients affected by cerebrovascular disease. Arguably, the impact of acquired brain injury on autoregulation may vary regionally depending on the specific pathology involved. Limitations The main limitation of the present study, as with most studies on MD, is the small sample size. Specifically, the subgroup analyses according to the underlying etiology of brain damage included only data from 17 SAH patients with 47 IHT, 4 ischemic stroke patients with 6 IHT, as well as 10 TBI patients with data from 20 IHT. Nonetheless, we found significant differences and new intriguing data which warrants further research on the topic. Materials and Methods The study protocol was approved by the scientific research ethics committee of Hospital Clinic of Barcelona, and informed consent was obtained from all participants and/or their legal guardians. The protection of the personal data of the participants, as well as the standards for good clinical practices, complied with what is contemplated in the Declaration of Helsinki. The identities of the participants were protected by anonymizing the data. The methodology of this report follows the recommendations of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Study population All neurocritical patients eligible for multimodal neuromonitoring were prospectively collected between January 2017 and January 2019. All clinical data of the patients and outcomes at discharge were prospectively registered in our database. Multimodal monitoring strategies were chosen by consensus between neuro-intensivists and neurosurgeons following an internal protocol, by which invasive intracranial pressure (ICP) monitoring of the most affected hemisphere, unilateral tissue oxygen pressure (PitO2) (most affected hemisphere) and bilateral brain metabolism (MD) are contemplated for vascular (SAH and ischemic stroke) patients with WFNS 4 or 5, and traumatic brain injury (TBI) patients with GCS ≤ 8. In these patients, two MD catheters were implanted, one in the hemisphere at higher risk of SBI ( side A ) and one in the contralateral hemisphere ( side B ). All IHT were recorded. For the analysis, IHT carried out for routine neuroimaging and surgical or endovascular treatments were considered. Conversely, IHT performed on unstable patients, patients with increased ICP or with pupillary changes were excluded. Likewise, patients who developed an acute worsening 24 hours after IHT or those who did not return to the ICU after performing the imaging because surgery was needed were also excluded. Clinical data The following clinical data were prospectively collected: sex, age, date and number of IHT per patient, surgical and/or endovascular treatments, and development of delayed cerebral ischemia (DCI). In subarachnoid haemorrhage (SAH) patients, radiological vasospasm was defined as the presence of a new-onset narrowing of a vessel, documented in either angio-CT or digital-subtraction angiography (DSA) 19 . Upon admission to the emergency department, the neurological state was recorded according to Glasgow Coma Scale (GCS). For TBI patients, GCS 3–8 was considered as severe; 9–12 as moderate; and 13–15 as mild. In vascular patients, WFNS IV-V was considered as severe; II-III as moderate; and I as mild. Upon discharge, patients were evaluated for midterm follow-up on day 90 after the SAH, stroke or TBI onset. This final evaluation included a neurological examination and a functional evaluation. Functional outcome was assessed with the modified Rankin Scale (mRS) or with the Glasgow Outcome Scale-Extended (GOSE) at 3 months through an in-person visit following structured questionnaires. A mRS of 0–2 was considered a good clinical outcome in vascular patients. A GOSE of 4 (moderate disability with some independence) or 5 (good recovery) was considered a good outcome for TBI patients, while 1 (death), 2 (vegetative state), or 3 (severe disability requiring daily care) were considered as poor outcome. Monitoring ICP was measured using an intraparenchymal catheter (Camino Intracranial Pressure Monitoring Kit, Integra). ICP data were collected in order to rule out intracranial hypertension crises before IHT. MD was measured using a 20kDa catheter (CMA 70; CMA/Microdialysis, Solna, Sweden) with a membrane length of 10 mm. The catheter was inserted intraparenchymal and bilaterally, to a depth of 2–3 cm, and connected to a perfusion pump (CMA 106; CMA/Microdialysis). Catheters were classified as side A , defined as the side with the greatest injury; and side B , defined as the side with the least damage. In patients with TBI, side A was the hemisphere with the largest contusion volume; in SAH patients, side A was the side of the ruptured aneurysm. In ambiguous cases (e.g., AcoA aneurysms), the side with the greatest subarachnoid or intraparenchymal blood volume was considered as side A 7,8 . For MD monitoring, the perfusion fluid (CMA mosm/Kg) was infused at a flow rate of 0.3 µl/minute. The microvials were collected and interpreted every hour, without interrupting the collection during transfer or procedures performed on the patient. Lactate, pyruvate, glycerol and glucose concentrations were analyzed by conventional microdialysis ISCUS FLEX H107263 analysis equipment (CMA600; CAM/Microdialysis). Bilateral MD data were collected 10 hours before transfer, during the transfer, and 10 hours after transfer, thus collecting a total of 21 hours of MD monitoring per patient and per transfer. Cases with < 80% of samples collected during the 21 hours were excluded. Data recording was stopped if one or both catheters consistently reported errors. Ischemic events were defined as those observations in which lactate/pyruvate ratio (LPR) was > 40 and glucose concentration < 0.7 mmol/L. All monitored patients underwent safety protocol. The safety protocol included: ( 1 ) Daily revision of catheter wounds to identify CSF leak or infection; ( 2 ) once the monitoring was stopped, the catheter tip was sent to the lab to detect microorganisms; ( 3 ) a CT was routinely performed after catheter placement in order to detect hemorrhagic complications related to the surgery and to confirm the location of the catheter tip. Intrahospital transfer IHT in our study were needed to perform an imaging technique (CT or angiography), or for surgical or neurointerventional treatment. The tomography equipment (where the CT was performed), the operating room and the angio-suite are in the same building as the ICU, but not on the same floor, making it necessary to use the elevator during transfer. In addition, it was necessary to change the patient's stretcher to carry out the transfer, both on the way to and from the CT or the operating room. During the IHT, patients were accompanied by a specialized neuro-intensivist and nursing staff from the same unit. The external ventricular drain was closed, and the ICP monitoring disconnected during transfer. In contrast, the MD perfusion pump remained active throughout the transfer. The duration of each IHT was registered prospectively. Technical complications recorded during transfer were collected retrospectively. Statistical analysis Statistical analyses were performed with SPSS v.25.0 and with Graph Prism v.5.0. For categorical or nominal values, a chi-square test was performed and for numerical values, a t-test was performed to compare the means of two groups. Before performing the test, the normal distribution of numerical values was evaluated with the Shapiro test to determine whether the normal distribution could be assumed. In normal distributed variables, the two-tailed paired t-test was applied. In those cases where the distribution was not normal, a non-parametric two-tailed Wilcoxon test was applied. The level of significance was established at a 0.05 level (2-sided). The graphs were obtained with Graph Prism v.5.0. Declarations Acknowledgments: We thank Dr Elisabeth Zavala for her acknowledgement of microdialysis, and to intensive care unit nurses of Hospital Clinic Barcelona for their collaboration into the project. Authorship confirmation/contribution statement : L.P., J.H., L.R, A.M, T.T, A.R-H., S.A., R.T., and J.E. contribute in conceptualization; L.P., J.H., and R.T. contribute to the methodology; L.P., J.H. and R.T. analysed the results; L.P., J.H., L.R, A.M, L.Z., T.T, A.R-H., S.A., and R.T. conceived the experiments and investigation; L.P., J.H., conducted the experiments; L.P., J.H., L.R, A.M, L.Z., T.T, A.R-H., S.A., and R.T. contribute to the writing - original draft; L.P., J.H., L.R, A.M, L.Z., T.T, A.R-H., S.A., and R.T. contribute to the visualization of article; A.R-H., S.A., and R.T. supervised the study. All authors reviewed the manuscript Author(s’) disclosure (Conflict of Interest) statement(s): The author(s) have no competing interest to disclose Funding statement: This research was funded by the Spanish Ministry of Economy and Competitiveness for a grant given to RT and SA [project PI19/00936 funded by Instituto de Salud Carlos III and co-funded by the European Regional Development Fund (ERDF)]. Data Availability: This study was registered after the study began. The study is registered at OSF with the number: osf.io/snmy5. The analysis plan was not formally pre-registered, but the team member with primary responsibility for the analysis (lead author, RT) certifies that the analysis plan was pre-specified. Data from this study are available in a public archive: osf.io/snmy5. There is no analytic code associated with this study. References Picetti E, Antonini MV, Lucchetti MC, et al. Intra-hospital transport of brain-injured patients: a prospective, observational study. 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Extracellular lactate and glucose alterations in the brain after head injury measured by microdialysis. Crit Care Med. 1999;27(9):1965–1973. doi: 10.1097/00003246-199909000-00041 Rostami E, Engquist H, Howells T, et al. Early low cerebral blood flow and high cerebral lactate: prediction of delayed cerebral ischemia in subarachnoid hemorrhage. J Neurosurg. 2018;128(6):1762–1770. doi: 10.3171/2016.11.JNS161140 Schmidt JM, Ko SB, Helbok R, et al. Cerebral perfusion pressure thresholds for brain tissue hypoxia and metabolic crisis after poor-grade subarachnoid hemorrhage. Stroke. 2011;42(5):1351–1356. doi: 10.1161/STROKEAHA.110.596874 Küchler J, Tronnier F, Smith E, Gliemroth J, Tronnier VM, Ditz C. The Impact of Intrahospital Transports on Brain Tissue Metabolism in Patients with Acute Brain Injury. Neurocrit Care. 2019;30(1):216–223. doi: 10.1007/s12028-018-0604-y De Rooij NK, Rinkel GJE, Dankbaar JW, Frijns CJM. Delayed cerebral ischemia after subarachnoid hemorrhage: a systematic review of clinical, laboratory, and radiological predictors. Stroke. 2013;44(1):43–54. doi: 10.1161/STROKEAHA.112.674291 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 28 Mar, 2024 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 02 Feb, 2024 Reviews received at journal 24 Jan, 2024 Reviewers agreed at journal 22 Jan, 2024 Reviews received at journal 25 Dec, 2023 Reviewers agreed at journal 03 Dec, 2023 Reviewers invited by journal 09 Oct, 2023 Editor assigned by journal 26 Sep, 2023 Editor invited by journal 28 Jul, 2023 Submission checks completed at journal 28 Jul, 2023 First submitted to journal 18 Jul, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3180261","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":222210627,"identity":"3291486e-b6b2-4bd1-8439-d68af055ccbb","order_by":0,"name":"Leire Pedrosa","email":"","orcid":"","institution":"IDIBAPS Biomedical Research Institute","correspondingAuthor":false,"prefix":"","firstName":"Leire","middleName":"","lastName":"Pedrosa","suffix":""},{"id":222210628,"identity":"a41a26c0-2d89-4c23-8246-43e30fb5784a","order_by":1,"name":"John Hoyos","email":"","orcid":"","institution":"Hospital Clinic of Barcelona","correspondingAuthor":false,"prefix":"","firstName":"John","middleName":"","lastName":"Hoyos","suffix":""},{"id":222210631,"identity":"896f3c1d-b046-4ee1-af7c-853bf8cfffb7","order_by":2,"name":"Luis Reyes","email":"","orcid":"","institution":"Hospital Clinic of Barcelona","correspondingAuthor":false,"prefix":"","firstName":"Luis","middleName":"","lastName":"Reyes","suffix":""},{"id":222210633,"identity":"10486782-4f10-413a-ba77-5dce1342a0ff","order_by":3,"name":"Alejandra Mosteiro","email":"","orcid":"","institution":"Hospital Clinic of Barcelona","correspondingAuthor":false,"prefix":"","firstName":"Alejandra","middleName":"","lastName":"Mosteiro","suffix":""},{"id":222210635,"identity":"61d5591f-5e14-478d-825b-d146a8cac5a1","order_by":4,"name":"Luigi Zattera","email":"","orcid":"","institution":"Hospital Clinic of Barcelona","correspondingAuthor":false,"prefix":"","firstName":"Luigi","middleName":"","lastName":"Zattera","suffix":""},{"id":222210637,"identity":"c50c01fe-d749-4d6e-8eb8-54e1fb7d7cb8","order_by":5,"name":"Thomaz Topczewski","email":"","orcid":"","institution":"Hospital Clinic of Barcelona","correspondingAuthor":false,"prefix":"","firstName":"Thomaz","middleName":"","lastName":"Topczewski","suffix":""},{"id":222210639,"identity":"8757c7d8-e71c-4da3-bd39-d517d6d0b51b","order_by":6,"name":"Ana Rodríguez-Hernández","email":"","orcid":"","institution":"Germans Trias i Pujol University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ana","middleName":"","lastName":"Rodríguez-Hernández","suffix":""},{"id":222210641,"identity":"aac257ce-4e32-48ad-866a-2f6eefbe787a","order_by":7,"name":"Sergio Amaro","email":"","orcid":"","institution":"Hospital Clinic of Barcelona","correspondingAuthor":false,"prefix":"","firstName":"Sergio","middleName":"","lastName":"Amaro","suffix":""},{"id":222210642,"identity":"a433ffb4-0aaa-4488-8781-cbe9892deb29","order_by":8,"name":"Ramon Torné","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAqklEQVRIiWNgGAWjYNCCCgYZNgbGBuIU84DJMww8MC0SxGlhbINqJUqLPXvvswcf59nx8Ek3N35gqLGrI2wLz3Fzw5nbknnYZA42SzAcSybCYRJpbNK82w7wsEkktgG9w0yklr9z4FrqidTC2ADXcpgILWeOsUn2HEsGaWmWSDh2XLKBkBb29jY2iR81dnLyM9IffvhQU81P0BZUkECi+lEwCkbBKBgFOAAAdWAtpwoLGckAAAAASUVORK5CYII=","orcid":"","institution":"Hospital Clinic of Barcelona","correspondingAuthor":true,"prefix":"","firstName":"Ramon","middleName":"","lastName":"Torné","suffix":""},{"id":222210643,"identity":"c5f2ac55-5c30-4a30-9f33-822e087902db","order_by":9,"name":"Joaquim Enseñat","email":"","orcid":"","institution":"Hospital Clinic of Barcelona","correspondingAuthor":false,"prefix":"","firstName":"Joaquim","middleName":"","lastName":"Enseñat","suffix":""}],"badges":[],"createdAt":"2023-07-18 06:29:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3180261/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3180261/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-024-57217-5","type":"published","date":"2024-03-28T15:01:47+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":40980973,"identity":"03e9d740-03f1-414c-81c1-ac1152d4a17b","added_by":"auto","created_at":"2023-08-02 22:18:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":84390,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStudy flowchart.\u003c/strong\u003eInitially, 33 neurocritical patients were included in the study. Two patients, which dead within 24 hours post-first IHT, were excluded. 31 patients were maintained in the study, with a total of 74 IHT, and were monitored by MD. Glucose, glycerol, lactate and pyruvate were analyzed from both cerebral hemispheres. Clinical data of 31 patients were recollected. IHT: Intrahospital transfer, MD: Microdialysis.\u003c/p\u003e","description":"","filename":"OnlineFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-3180261/v1/f849647130d2a69fb55da929.png"},{"id":40980360,"identity":"9418a90b-2cb7-4d92-b185-c859adada462","added_by":"auto","created_at":"2023-08-02 22:10:57","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":79938,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eBiochemistry metabolites from both cerebral hemispheres analyzed by microdialysis. \u003c/strong\u003eHourly values of cerebral glucose (a), cerebral glycerol (b), and cerebral lactate/pyruvate ratio (c), 10 h before and after the intrahospital transfer of both hemispheres. The interstitial liquid was analyzed from the affected hemisphere (A, red) and non-affected hemisphere (B, green). TBI: Traumatic brain injury LPR: Lactate/pyruvate ratio.\u003c/p\u003e","description":"","filename":"OnlineFigure2.png","url":"https://assets-eu.researchsquare.com/files/rs-3180261/v1/f22e157c0a68eddf5b17c283.png"},{"id":40980362,"identity":"53fadc36-efce-47d9-b358-7ad18622564d","added_by":"auto","created_at":"2023-08-02 22:10:57","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":93686,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eBiochemistry metabolites from both cerebral hemispheres analyzed by microdialysis of TBI and vascular patients.\u003c/strong\u003eHourly values of cerebral glucose (a), cerebral glycerol (b), and cerebral lactate/pyruvate ratio (c), 10 h before and after the intrahospital transfer, comparing both hemispheres (affected hemisphere (A; red and green) and non-affected hemisphere (B; turquoise and pink) of TBI and vascular patients. TBI: Traumatic brain injuty, LPR: Lactate/pyruvate ratio.\u003c/p\u003e","description":"","filename":"OnlineFigure3.png","url":"https://assets-eu.researchsquare.com/files/rs-3180261/v1/a3e955f596b0ad48d470f5ec.png"},{"id":53869784,"identity":"acdc33ee-a54b-4b78-acf7-af23c8a896da","added_by":"auto","created_at":"2024-04-01 15:11:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":863959,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3180261/v1/3e8dd2bd-aba4-4fb0-a9af-f0aca5cc0f21.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Brain metabolism response to intrahospital transfers in neurocritical ill patients: Does the microdialysis probe location matter?","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIntrahospital transfer (IHT) is a routine process in intensive care units (ICU) for neurocritical patients\u003csup\u003e1\u003c/sup\u003e. Actually, at least two IHTs are needed when an advanced imaging study or surgical or interventional treatments are deemed necessary. Most centers try to minimize the number of IHTs of neurocritical patients, as they may result in airway management problems, medication disruption, positional changes, and ventricular drainage discontinuation\u003csup\u003e2,3\u0026ndash;5\u003c/sup\u003e. These situations experienced during IHTs may cause an increase in intracranial pressure (ICP) and/or brain hypoxia leading to secondary brain injury (SBI), thus worsening the clinical outcome.\u003c/p\u003e \u003cp\u003eMetabolic dysregulations may reflect this iatrogenic SBI and therefore cerebral microdialysis (MD) monitoring has been one of the tools used to investigate the consequences of IHT in neurocritical patients. However, the results obtained so far are diverse and contradictory, ranging from the absence of metabolite changes during or after IHT to increases in glycerol, lactate and pyruvate levels immediately after IHT\u003csup\u003e6\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn these previous studies, the MD monitorization was conducted unilaterally, specifically in the hemisphere defined as the one most damaged. Nevertheless, the difficulty in defining the hemisphere at higher risk is well known\u003csup\u003e7\u0026ndash;10\u003c/sup\u003e and relevant information may be overlooked when only one hemisphere is monitored\u003csup\u003e11\u003c/sup\u003e. The purpose of our study is to quantify the effect of IHT on brain metabolism of neurocritical patients monitored with bilateral MD probes and to assess the differential impact of the underlying pathology on the presence of bilateral brain metabolism.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eOverall, 76 IHT from 33 patients were collected. Three IHT corresponding to two patients who died within 24 hours of IHT were excluded from the final analysis. Of the remaining 73 IHT analyzed, the mean transfer time was 21\u0026thinsp;\u0026plusmn;\u0026thinsp;6 minutes. A total of 89% (65/73) of IHT were done to obtain a CT, 9.6% (7/73) to acquire an angiography, and 1.4% (1/73) to perform an endovascular treatment (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient characteristics and transfers\u003c/h2\u003e \u003cp\u003eOut of the 31 patients analyzed, 17 (17/31; 55%) were male. The mean age was 48 years (range 20\u0026ndash;72) and the mean GCS at admission was 7 (range 3\u0026ndash;14). Most of the patients (20/31; 69%) were admitted in coma (GCS\u0026thinsp;\u0026le;\u0026thinsp;8). The cause of the brain injury was vascular pathology in 21/31 cases (68%) and TBI in 10/31 (32%). Out of the 31 patients, 16 (52%) required surgical intervention, 5 (16%) required a surgical evacuation of an intraparenchymal hematoma, 3 (10%) underwent a decompressive craniectomy, 4 (13%) needed a craniotomy for aneurysm clipping, and 3 (10%) more required aneurysms clipping plus hematoma drainage (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). A good clinical outcome was observed in 32% (9/28) of the patients at hospital discharge and in 76% (16/21) at 3 months follow-up.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003cb\u003eDemographic and Clinical variables of the patients included in the study.\u003c/b\u003e Data are first described in the global group and then categorized according to the pathological admission diagnosis (vascular or traumatic brain injury). TBI: Traumatic brain injury, GCS: Glasgow Coma Scale (GCS), mRS: modified Rankin Scale score, IHT: Intrahospital transfer, DCI: Delayed cerebral ischemia. The table shows the p-value obtained by comparing the subjects in each variable in each pathological group with the chi-square test.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eVascular (n\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTBI (n\u0026thinsp;=\u0026thinsp;10)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMale\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (54.83%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (42.90%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 (80.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.052\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMean (min-max)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (20\u0026ndash;72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e54 (37\u0026ndash;72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32 (20\u0026ndash;61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eGCS at hospital admission\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eSevere (3\u0026ndash;8)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (68.97%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (63.16%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 (80.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eModerate (9\u0026ndash;12)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (17.24%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (21.05%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (10.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eGood (13\u0026ndash;15)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (13.79%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (15.79%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (10.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e\u003cb\u003eSurgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNon-surgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (51.61%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (47.61%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (60.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"4\" rowspan=\"5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eHematoma drainage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (16.13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (19.05%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (10.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAneurysm clipping plus hematoma drainage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (9.68%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (14.29%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eDecompressive craniectomy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (9.68%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (30.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAneurysm clipping\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (12.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (19.05%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eDCI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNon-DCI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (70.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (70.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eClinical\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (10.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (10.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eRadiological\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (20.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (20.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eNumber of IHT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (29.03%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (28.57%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (30.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.249\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (32.26%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (23.81%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (50.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e3 or more\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (38.71%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (47.62%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (20.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eStatus on the day of discharge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eBad\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (67.86%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (84.21%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (33.33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eGood\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (32.14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (15.79%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (66.67%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eOutcome at 3 months\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eBad\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (23.81%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (28.57%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (14.29%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eGood\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (76.19%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (71.43%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (85.71%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eMost of the patients (12/31; 3%) underwent 3 or more transfers, 10 (10/31; 32%) patients had 2 transfers, and 9 patients (9/31; 29%) had only one transfer. Those patients who required a higher number of transfers were predominantly cerebrovascular cases (10 SAH vs. 2 TBI patients). The most frequent number of transfers in TBI patients was 2 (5/10; 50%), whereas most vascular patients (10/21; 48%) required 3 or more transfers (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eBrain Metabolism\u003c/h2\u003e \u003cp\u003eBefore IHT, the levels of glycerol were higher on \u003cem\u003eside A\u003c/em\u003e than on \u003cem\u003eside B\u003c/em\u003e (mean 300 vs 244 \u0026micro;mol/l, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01), whereas the levels of LPR (mean 35 vs 33) and glucose (1.96 vs 1.90 mmol/l) were similar in both hemispheres (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). After IHT, our data showed a decrease in glucose (1.95 mmol/l pre-IHT vs 1.72 mmol/l post-IHT, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), an increase in glycerol (300 \u0026micro;mol/l pre-IHT vs 392 \u0026micro;mol/l post-IHT, p\u0026thinsp;=\u0026thinsp;0.001) and an increase in LPR (35 pre-IHT vs 43 post-IHT, p\u0026thinsp;=\u0026thinsp;0.005) on \u003cem\u003eside A\u003c/em\u003e, in comparison with \u003cem\u003eside B\u003c/em\u003e. Similarly, we also observed a decrease in glucose (1.90 mmol/l pre-IHT vs 1.70 mmol/l post-IHT, p\u0026thinsp;=\u0026thinsp;0.011), and a significant increase in glycerol (245 \u0026micro;mol/l pre-IHT vs 272 \u0026micro;mol/l post-IHT, p\u0026thinsp;=\u0026thinsp;0.005) on \u003cem\u003eside B\u003c/em\u003e. In contrast to \u003cem\u003eside A\u003c/em\u003e, on \u003cem\u003eside B\u003c/em\u003e no statistically significant differences in LPR were observed (33 pre-IHT vs 32 post-IHT, p\u0026thinsp;=\u0026thinsp;0.658) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In addition, a statistically significant increase in lactate was observed on \u003cem\u003eside A\u003c/em\u003e, while this difference was absent on \u003cem\u003eside B\u003c/em\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003cb\u003eMetabolites analyzed by MD in both hemispheres pre- and post-IHT.\u003c/b\u003e Mean concentration of each metabolite and SD from affected (A side) and non-affected (B side) hemispheres were shown. The p-value was obtained by comparing the values pre and post-IHT with the t-test Student. IHT: Intrahospital transfer, LPR: Lactate/pyruvate ratio.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eA side\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eB side\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePre IHT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePost IHT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePre IHT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePost IHT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGlucose (mmol/L)\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.95\u0026thinsp;\u0026plusmn;\u0026thinsp;0.921\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.72\u0026thinsp;\u0026plusmn;\u0026thinsp;0.915\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e1.90\u0026thinsp;\u0026plusmn;\u0026thinsp;1.398\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e1.70\u0026thinsp;\u0026plusmn;\u0026thinsp;1.168\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGlycerol (Umol/L)\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e300.27\u0026thinsp;\u0026plusmn;\u0026thinsp;303.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e391.83\u0026thinsp;\u0026plusmn;\u0026thinsp;321.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e244.69\u0026thinsp;\u0026plusmn;\u0026thinsp;208.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e272.30\u0026thinsp;\u0026plusmn;\u0026thinsp;190.775\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePyruvate (Umol/L)\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e126.61\u0026thinsp;\u0026plusmn;\u0026thinsp;68.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e133.99\u0026thinsp;\u0026plusmn;\u0026thinsp;64.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e109.49\u0026thinsp;\u0026plusmn;\u0026thinsp;56.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e116.18\u0026thinsp;\u0026plusmn;\u0026thinsp;55.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLactate (mmol/L)\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e4.16\u0026thinsp;\u0026plusmn;\u0026thinsp;3.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4.95\u0026thinsp;\u0026plusmn;\u0026thinsp;3.376\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e3.78\u0026thinsp;\u0026plusmn;\u0026thinsp;3.089\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e3.77\u0026thinsp;\u0026plusmn;\u0026thinsp;2.691\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.066\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePyruvate (Umol/L)\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e126.61\u0026thinsp;\u0026plusmn;\u0026thinsp;68.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e133.99\u0026thinsp;\u0026plusmn;\u0026thinsp;64.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e109.49\u0026thinsp;\u0026plusmn;\u0026thinsp;56.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e116.18\u0026thinsp;\u0026plusmn;\u0026thinsp;55.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLPR\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e35.01\u0026thinsp;\u0026plusmn;\u0026thinsp;27.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e42.57\u0026thinsp;\u0026plusmn;\u0026thinsp;46.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e33.06\u0026thinsp;\u0026plusmn;\u0026thinsp;17.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e31.89\u0026thinsp;\u0026plusmn;\u0026thinsp;13.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.658\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eRegarding the results obtained in the most affected side (\u003cem\u003eside A\u003c/em\u003e) according to the underlying pathology (vascular vs TBI), we found a decreased level of glucose before and after IHT in both pathologies: TBI patients (1.89 mmol/l pre-IHT vs 1.62 mmol/l post-IHT, p\u0026thinsp;=\u0026thinsp;0.016) and vascular patients (1.98 mmol/l pre-IHT vs 1.77 mmol/l post-IHT, p\u0026thinsp;=\u0026thinsp;0.002). Besides, there was also an increase in LPR in TBI patients (28 pre-IHT vs 36 post-IHT, p\u0026thinsp;=\u0026thinsp;0.055) and in the vascular pathology group (38 pre-IHT vs 45 post-IHT, p\u0026thinsp;=\u0026thinsp;0.028) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003cb\u003eMetabolites analyzed by MD in both hemispheres pre- and post-IHT.\u003c/b\u003e Mean concentration of each metabolite and SD from affected (A side) and non-affected (B side) hemispheres were shown. Patients were grouped according to the pathological diagnosis (vascular and traumatic brain injury). The p-value was obtained by comparing the values pre- and post-IHT with the t-test Student. TBI: Traumatic brain injury, IHT: Intrahospital transfer, LPR: Lactate/pyruvate ratio.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eA side\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eB side\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMetabolite\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePathology\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePre IHT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePost IHT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePre IHT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePost IHT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eGlucose (mmol/L)\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eTBI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.888\u0026thinsp;\u0026plusmn;\u0026thinsp;1.048\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e1.624\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9814\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e2.069\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9855\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e2.099\u0026thinsp;\u0026plusmn;\u0026thinsp;1.427\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.225\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eVascular\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.982\u0026thinsp;\u0026plusmn;\u0026thinsp;0.870\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e1.766\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8870\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e1.847\u0026thinsp;\u0026plusmn;\u0026thinsp;1.515\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e1.553\u0026thinsp;\u0026plusmn;\u0026thinsp;1.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eGlycerol (Umol/L)\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eTBI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e300.9\u0026thinsp;\u0026plusmn;\u0026thinsp;380.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e376.0\u0026thinsp;\u0026plusmn;\u0026thinsp;400.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e219.1\u0026thinsp;\u0026plusmn;\u0026thinsp;266.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e244.8\u0026thinsp;\u0026plusmn;\u0026thinsp;219.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.059\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eVascular\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e300.0\u0026thinsp;\u0026plusmn;\u0026thinsp;271.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e346.3\u0026thinsp;\u0026plusmn;\u0026thinsp;288.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e254.2\u0026thinsp;\u0026plusmn;\u0026thinsp;181.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e282.5\u0026thinsp;\u0026plusmn;\u0026thinsp;178.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.025\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eLactate (mmol/L)\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eTBI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.470\u0026thinsp;\u0026plusmn;\u0026thinsp;3.642\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e4.305\u0026thinsp;\u0026plusmn;\u0026thinsp;3.904\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e2.366\u0026thinsp;\u0026plusmn;\u0026thinsp;1.651\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e2.378\u0026thinsp;\u0026plusmn;\u0026thinsp;1.109\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.059\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eVascular\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4.421\u0026thinsp;\u0026plusmn;\u0026thinsp;2.748\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e5.186\u0026thinsp;\u0026plusmn;\u0026thinsp;3.132\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e4.311\u0026thinsp;\u0026plusmn;\u0026thinsp;3.308\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e4.292\u0026thinsp;\u0026plusmn;\u0026thinsp;2.897\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.242\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003ePyruvate (Umol/L)\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eTBI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e116.8\u0026thinsp;\u0026plusmn;\u0026thinsp;79.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e123.2\u0026thinsp;\u0026plusmn;\u0026thinsp;81.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.185\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e92.25\u0026thinsp;\u0026plusmn;\u0026thinsp;44.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e91.77\u0026thinsp;\u0026plusmn;\u0026thinsp;31.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.255\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eVascular\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e130.3\u0026thinsp;\u0026plusmn;\u0026thinsp;64.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e138.0\u0026thinsp;\u0026plusmn;\u0026thinsp;56.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e115.9\u0026thinsp;\u0026plusmn;\u0026thinsp;58.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e125.2\u0026thinsp;\u0026plusmn;\u0026thinsp;59.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eLPR\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eTBI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e27.75\u0026thinsp;\u0026plusmn;\u0026thinsp;12.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e35.73\u0026thinsp;\u0026plusmn;\u0026thinsp;23.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.055\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e25.20\u0026thinsp;\u0026plusmn;\u0026thinsp;9.927\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e27.83\u0026thinsp;\u0026plusmn;\u0026thinsp;9.064\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.253\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eVascular\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e37.71\u0026thinsp;\u0026plusmn;\u0026thinsp;31.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e45.11\u0026thinsp;\u0026plusmn;\u0026thinsp;52.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.028\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e35.98\u0026thinsp;\u0026plusmn;\u0026thinsp;18.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e33.41\u0026thinsp;\u0026plusmn;\u0026thinsp;14.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.243\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eMeanwhile, in \u003cem\u003eside B\u003c/em\u003e, a number of differences were observed between pre- and post-IHT periods in the vascular pathology group including increases in glycerol levels (254 \u0026micro;mol/l pre-IHT vs 283 \u0026micro;mol/l post-IHT, p\u0026thinsp;=\u0026thinsp;0.025) and pyruvate levels (116 \u0026micro;mol/l pre-IHT vs 125 \u0026micro;mol/l post-IHT, p\u0026thinsp;=\u0026thinsp;0.004), and decreases in glucose levels (1.85 mmol/l pre-IHT vs. 1.55 mmol/l post-IHT, p\u0026thinsp;=\u0026thinsp;0.017). Conversely, no statistically significant differences were found in the LPR (36 pre-IHT vs 33 post-IHT, p\u0026thinsp;=\u0026thinsp;0.243) nor in lactate levels (4.31 mmol/l pre-IHT vs 4.29 mmol/l post-IHT, p\u0026thinsp;=\u0026thinsp;0.242). Interestingly, in vascular patients, the LPR on \u003cem\u003eside B\u003c/em\u003e did not change after the transfer, as compared to the increase observed on \u003cem\u003eside A\u003c/em\u003e. In the TBI group, no differences were seen in the metabolic parameters on \u003cem\u003eside B\u003c/em\u003e before and after IHT (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe clinical repercussions of IHT in neurocritical patients have been debated over the last years\u003csup\u003e1,2\u003c/sup\u003e, with some authors advocating keeping the patient in ICU as much as possible thus reducing transfer outside the unit. However, balancing the potential risk and benefits of IHT is not an easy task. On one hand, diagnostic tests and therapeutic interventions requiring an IHT may be lifesaving. On the other hand, the metabolic response of the brain to IHT may cause SBI thus hindering the odds of patient recovery. However, the brain response to IHT is not well understood, especially regarding the less-affected hemisphere, which is usually not monitored. Furthermore, data on whether this response may vary depending on the underlying pathology is also lacking. In this scenario, the present study aimed to assess the impact of IHT on brain metabolism in neurocritical patients through the use of bilateral MD monitoring. Interestingly, our results suggest that IHT affects the brain metabolism not only in the hemisphere with more damage (side A), but it also on the side with less initial injury (side B). Moreover, we observed that this \u003cem\u003eside B\u003c/em\u003e impairment seems to vary according to the underlying pathology. Therefore, this \u0026ldquo;contralateral\u0026rdquo; response to IHT might be significant in the patient\u0026rsquo;s overall prognosis and could be of greater importance in pathologies with more diffuse damage.\u003c/p\u003e \u003cp\u003eOur findings revealed significant effects of IHT on cerebral metabolism, particularly on the more damaged side (A). Specifically, on \u003cem\u003eside A\u003c/em\u003e we observed after IHT a notable increase in glycerol levels, a significant decrease in glucose levels, and a significant increase in the LPR. These changes may be attributed to episodes of hypermetabolism or \u0026ldquo;metabolic crises\u0026rdquo;, which have been linked to unfavorable outcomes \u003csup\u003e12\u0026ndash;14\u003c/sup\u003e. The stress induced by IHT could be responsible for the observed decrease in glucose levels though the enhancement of anaerobic glycolysis and eventually resulting in an elevated LPR \u003csup\u003e15\u003c/sup\u003e. Importantly, an elevated LPR has been associated with the development of delayed cerebral ischemia (DCI) in subarachnoid hemorrhage (SAH) patients, suggesting that IHT may increase the risk of DCI following transfers \u003csup\u003e16\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn previous studies \u003csup\u003e6,8\u0026ndash;10,17,18\u003c/sup\u003e, similar results were obtained regarding the increase in glycerol after IHT. However, in contrast with our observed data some of these studies did not find variations in other parameters of brain metabolism. K\u0026uuml;chler et al. found no difference in metabolite levels before and after IHT in intracranial hemorrhage (ICH), subarachnoid hemorrhage (SAH) and brain trauma. The study concluded that although most of the metabolites analyzed increased after IHT, these changes were not related to incident metabolic crisis\u003csup\u003e18\u003c/sup\u003e. Contrarily and in line with our results, Hosman et al. found significant increases in difference glycerol, lactate and pyruvate levels after IHT, suggesting that IHT affects the brain metabolism of neurocritical patients\u003csup\u003e6\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe main novelty provided by our investigation was the assessment of the effects of IHT on cerebral metabolism in patients monitored with bilateral MD. Similar to the metabolite changes found on side A, we also observed on side B a significant increase in post-transfer glycerol levels, indicating acute neuronal damage. However, while glucose levels decreased significantly after transfer, no significant changes in the LPR were observed. This suggests that \u003cem\u003eside B\u003c/em\u003e did not experience the same level of stress-induced anaerobic glycolysis as that observed on \u003cem\u003eside A.\u003c/em\u003e Furthermore, analyzing metabolism disturbances by pathology, we observed that TBI patients presented a significant decrease in glucose, an increase in glycerol and an increase in lactate (without a significant increase in the LPR) only on \u003cem\u003eside A.\u003c/em\u003e Meanwhile, on \u003cem\u003eside B\u003c/em\u003e, no significant differences were observed in these values. Conversely, in the vascular pathology group, several metabolite changes were noted. On \u003cem\u003eside A\u003c/em\u003e we found a significant decrease in glucose levels, an increase in glycerol, in lactate and in the LPR, while on \u003cem\u003eside B\u003c/em\u003e a significant increase in glucose, glycerol and pyruvate levels was observed. These results suggest that \u003cem\u003eside B\u003c/em\u003e in vascular pathology is more prone to local metabolic disturbances than \u003cem\u003eside B\u003c/em\u003e in TBI. Presumably, in TBI the brain damage is more local than in cerebrovascular pathology, and the contralateral hemisphere maintains a certain capacity to autoregulate under stress conditions. Contrarily, in SAH patients the dysregulation seems to be more global, putting both hemispheres at risk of developing secondary damage. Therefore, our findings suggest that some neurocritical patients may benefit more from bilateral monitoring than others. Arguably, in patients affected by pathologies of vascular origin such as SAH, bilateral monitoring may help for enhancing the detection of ischemic events.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOur results suggest that IHT may lead to disturbances in the brain metabolism of neurocritical ill patients, as evidenced by the changes observed in MD registries. The metabolic alterations seemed to be more pronounced on the hemisphere with more primary damage than in the contralateral one, particularly in patients with TBI. However, it is important to note that IHT may also cause some degree of impairment, albeit less severe, on the contralateral hemisphere, especially in patients affected by cerebrovascular disease. Arguably, the impact of acquired brain injury on autoregulation may vary regionally depending on the specific pathology involved.\u003c/p\u003e\n\u003ch3\u003eLimitations\u003c/h3\u003e\n\u003cp\u003eThe main limitation of the present study, as with most studies on MD, is the small sample size. Specifically, the subgroup analyses according to the underlying etiology of brain damage included only data from 17 SAH patients with 47 IHT, 4 ischemic stroke patients with 6 IHT, as well as 10 TBI patients with data from 20 IHT. Nonetheless, we found significant differences and new intriguing data which warrants further research on the topic.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e The study protocol was approved by the scientific research ethics committee of Hospital Clinic of Barcelona, and informed consent was obtained from all participants and/or their legal guardians. The protection of the personal data of the participants, as well as the standards for good clinical practices, complied with what is contemplated in the Declaration of Helsinki. The identities of the participants were protected by anonymizing the data. The methodology of this report follows the recommendations of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.\u003c/p\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eAll neurocritical patients eligible for multimodal neuromonitoring were prospectively collected between January 2017 and January 2019. All clinical data of the patients and outcomes at discharge were prospectively registered in our database. Multimodal monitoring strategies were chosen by consensus between neuro-intensivists and neurosurgeons following an internal protocol, by which invasive intracranial pressure (ICP) monitoring of the most affected hemisphere, unilateral tissue oxygen pressure (PitO2) (most affected hemisphere) and bilateral brain metabolism (MD) are contemplated for vascular (SAH and ischemic stroke) patients with WFNS 4 or 5, and traumatic brain injury (TBI) patients with GCS\u0026thinsp;\u0026le;\u0026thinsp;8. In these patients, two MD catheters were implanted, one in the hemisphere at higher risk of SBI (\u003cem\u003eside A\u003c/em\u003e) and one in the contralateral hemisphere (\u003cem\u003eside B\u003c/em\u003e).\u003c/p\u003e \u003cp\u003eAll IHT were recorded. For the analysis, IHT carried out for routine neuroimaging and surgical or endovascular treatments were considered. Conversely, IHT performed on unstable patients, patients with increased ICP or with pupillary changes were excluded. Likewise, patients who developed an acute worsening 24 hours after IHT or those who did not return to the ICU after performing the imaging because surgery was needed were also excluded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eClinical data\u003c/h2\u003e \u003cp\u003eThe following clinical data were prospectively collected: sex, age, date and number of IHT per patient, surgical and/or endovascular treatments, and development of delayed cerebral ischemia (DCI). In subarachnoid haemorrhage (SAH) patients, radiological vasospasm was defined as the presence of a new-onset narrowing of a vessel, documented in either angio-CT or digital-subtraction angiography (DSA)\u003csup\u003e19\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eUpon admission to the emergency department, the neurological state was recorded according to Glasgow Coma Scale (GCS). For TBI patients, GCS 3\u0026ndash;8 was considered as severe; 9\u0026ndash;12 as moderate; and 13\u0026ndash;15 as mild. In vascular patients, WFNS IV-V was considered as severe; II-III as moderate; and I as mild. Upon discharge, patients were evaluated for midterm follow-up on day 90 after the SAH, stroke or TBI onset. This final evaluation included a neurological examination and a functional evaluation. Functional outcome was assessed with the modified Rankin Scale (mRS) or with the Glasgow Outcome Scale-Extended (GOSE) at 3 months through an in-person visit following structured questionnaires. A mRS of 0\u0026ndash;2 was considered a good clinical outcome in vascular patients. A GOSE of 4 (moderate disability with some independence) or 5 (good recovery) was considered a good outcome for TBI patients, while 1 (death), 2 (vegetative state), or 3 (severe disability requiring daily care) were considered as poor outcome.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eMonitoring\u003c/h2\u003e \u003cp\u003eICP was measured using an intraparenchymal catheter (Camino Intracranial Pressure Monitoring Kit, Integra). ICP data were collected in order to rule out intracranial hypertension crises before IHT. MD was measured using a 20kDa catheter (CMA 70; CMA/Microdialysis, Solna, Sweden) with a membrane length of 10 mm. The catheter was inserted intraparenchymal and bilaterally, to a depth of 2\u0026ndash;3 cm, and connected to a perfusion pump (CMA 106; CMA/Microdialysis). Catheters were classified as \u003cem\u003eside A\u003c/em\u003e, defined as the side with the greatest injury; and \u003cem\u003eside B\u003c/em\u003e, defined as the side with the least damage. In patients with TBI, \u003cem\u003eside A\u003c/em\u003e was the hemisphere with the largest contusion volume; in SAH patients, \u003cem\u003eside A\u003c/em\u003e was the side of the ruptured aneurysm. In ambiguous cases (e.g., AcoA aneurysms), the side with the greatest subarachnoid or intraparenchymal blood volume was considered as \u003cem\u003eside A\u003c/em\u003e \u003csup\u003e7,8\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eFor MD monitoring, the perfusion fluid (CMA mosm/Kg) was infused at a flow rate of 0.3 \u0026micro;l/minute. The microvials were collected and interpreted every hour, without interrupting the collection during transfer or procedures performed on the patient. Lactate, pyruvate, glycerol and glucose concentrations were analyzed by conventional microdialysis ISCUS FLEX H107263 analysis equipment (CMA600; CAM/Microdialysis). Bilateral MD data were collected 10 hours before transfer, during the transfer, and 10 hours after transfer, thus collecting a total of 21 hours of MD monitoring per patient and per transfer. Cases with \u0026lt;\u0026thinsp;80% of samples collected during the 21 hours were excluded.\u003c/p\u003e \u003cp\u003eData recording was stopped if one or both catheters consistently reported errors. Ischemic events were defined as those observations in which lactate/pyruvate ratio (LPR) was \u0026gt;\u0026thinsp;40 and glucose concentration\u0026thinsp;\u0026lt;\u0026thinsp;0.7 mmol/L.\u003c/p\u003e \u003cp\u003eAll monitored patients underwent safety protocol. The safety protocol included: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Daily revision of catheter wounds to identify CSF leak or infection; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) once the monitoring was stopped, the catheter tip was sent to the lab to detect microorganisms; (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) a CT was routinely performed after catheter placement in order to detect hemorrhagic complications related to the surgery and to confirm the location of the catheter tip.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eIntrahospital transfer\u003c/h2\u003e \u003cp\u003eIHT in our study were needed to perform an imaging technique (CT or angiography), or for surgical or neurointerventional treatment. The tomography equipment (where the CT was performed), the operating room and the angio-suite are in the same building as the ICU, but not on the same floor, making it necessary to use the elevator during transfer. In addition, it was necessary to change the patient's stretcher to carry out the transfer, both on the way to and from the CT or the operating room. During the IHT, patients were accompanied by a specialized neuro-intensivist and nursing staff from the same unit. The external ventricular drain was closed, and the ICP monitoring disconnected during transfer. In contrast, the MD perfusion pump remained active throughout the transfer. The duration of each IHT was registered prospectively. Technical complications recorded during transfer were collected retrospectively.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed with SPSS v.25.0 and with Graph Prism v.5.0. For categorical or nominal values, a chi-square test was performed and for numerical values, a t-test was performed to compare the means of two groups. Before performing the test, the normal distribution of numerical values was evaluated with the Shapiro test to determine whether the normal distribution could be assumed. In normal distributed variables, the two-tailed paired t-test was applied. In those cases where the distribution was not normal, a non-parametric two-tailed Wilcoxon test was applied. The level of significance was established at a 0.05 level (2-sided). The graphs were obtained with Graph Prism v.5.0.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cu\u003eAcknowledgments:\u003c/u\u003e\u003c/strong\u003e We thank Dr Elisabeth Zavala for her acknowledgement of microdialysis, and to intensive care unit nurses of Hospital Clinic Barcelona for their collaboration into the project.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eAuthorship confirmation/contribution statement\u003c/u\u003e\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eL.P., J.H., L.R, A.M, T.T, A.R-H., S.A., R.T., and J.E. contribute in conceptualization; L.P., J.H., and R.T. contribute to the methodology; L.P., J.H. and R.T. analysed the results; L.P., J.H., L.R, A.M, L.Z., T.T, A.R-H., S.A., and R.T. conceived the experiments and investigation; \u0026nbsp;L.P., J.H., conducted the experiments; L.P., J.H., L.R, \u0026nbsp;A.M, L.Z., T.T, A.R-H., S.A., and R.T. contribute to the writing - original draft; L.P., J.H., L.R, A.M, L.Z., T.T, A.R-H., S.A., and R.T. contribute to the visualization of article;\u0026nbsp;A.R-H., S.A., and R.T. supervised the study. All authors reviewed the manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eAuthor(s\u0026rsquo;) disclosure\u0026nbsp;(Conflict of Interest) statement(s):\u003c/u\u003e\u003c/strong\u003e The author(s) have no competing interest to disclose\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eFunding statement:\u003c/u\u003e\u003c/strong\u003e This research was funded by the Spanish Ministry of Economy and Competitiveness for a grant given to RT and SA [project PI19/00936 funded by Instituto de Salud Carlos III and co-funded by the European Regional Development Fund (ERDF)].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eData Availability:\u003c/u\u003e\u003c/strong\u003e This study was registered after the study began. The study is registered at OSF with the number: osf.io/snmy5. The analysis plan was not formally pre-registered, but the team member with primary responsibility for the analysis (lead author, RT) certifies that the analysis plan was pre-specified. Data from this study are available in a public archive: osf.io/snmy5. There is no analytic code associated with this study. \u003cstrong\u003e\u003cu\u003e\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePicetti E, Antonini MV, Lucchetti MC, et al. Intra-hospital transport of brain-injured patients: a prospective, observational study. Neurocrit Care. 2013;18(3):298\u0026ndash;304. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/S12028-012-9802-1\u003c/span\u003e\u003cspan address=\"10.1007/S12028-012-9802-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLahner D, Nikolic A, Marhofer P, et al. 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Delayed cerebral ischemia after subarachnoid hemorrhage: a systematic review of clinical, laboratory, and radiological predictors. Stroke. 2013;44(1):43\u0026ndash;54. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/STROKEAHA.112.674291\u003c/span\u003e\u003cspan address=\"10.1161/STROKEAHA.112.674291\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"microdialysis monitoring, brain metabolism, intrahospital transfer, neurocritical patients, traumatic brain injury, neurovascular disease","lastPublishedDoi":"10.21203/rs.3.rs-3180261/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3180261/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIntrahospital transfer (IHT), a routine in the management of neurocritical patients requiring imaging or interventions, might affect brain metabolism. Studies about IHT effects using microdialysis (MD) have produced conflicting results. In these studies, only the most damaged hemisphere was monitored, and those may not reflect the impact of IHT on overall brain metabolism, nor do they address differences between the hemispheres. Herein we aimed to quantify the effect of IHT on brain metabolism by monitoring both hemispheres with bilateral MD. In this study, 31 patients were included, with a total of 73 IHT. Glucose, glycerol, pyruvate and lactate were measured by MD in both hemispheres for 10 hours pre- and post-IHT. Alterations in metabolite levels after IHT were observed on both hemispheres; although these changes were more marked in hemisphere \u003cem\u003eA\u003c/em\u003e (most damaged) than \u003cem\u003eB\u003c/em\u003e (less damaged). Changes in metabolite levels in hemisphere \u003cem\u003eB\u003c/em\u003e were more evident in cerebrovascular than in traumatic brain injury patients. Our results suggest that, brain metabolism is altered after an IHT of neurocritical ill patients, particularly but not limited to the damaged hemisphere. Bilateral monitorization may be more sensitive than unilateral monitorization for detecting metabolic disturbances not directly related to the course of the disease.\u003c/p\u003e","manuscriptTitle":"Brain metabolism response to intrahospital transfers in neurocritical ill patients: Does the microdialysis probe location matter?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-08-02 22:10:52","doi":"10.21203/rs.3.rs-3180261/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-02-02T12:42:13+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-01-24T19:18:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"d792c89d-56fd-4391-8d21-5af879975f8e","date":"2024-01-22T15:06:44+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-12-25T13:36:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"70342e55-8758-4e52-aeb3-b6b6ff7667fa_SNPRID","date":"2023-12-03T12:09:10+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-10-09T07:12:33+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-09-26T09:29:11+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2023-07-28T05:50:03+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-07-28T05:47:35+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2023-07-18T06:19:23+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9f616d26-c87d-481c-bdaf-ab543c3e69be","owner":[],"postedDate":"August 2nd, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":23622613,"name":"Biological sciences/Neuroscience"},{"id":23622614,"name":"Health sciences/Biomarkers"},{"id":23622615,"name":"Health sciences/Medical research"},{"id":23622616,"name":"Health sciences/Neurology"}],"tags":[],"updatedAt":"2024-04-01T15:07:30+00:00","versionOfRecord":{"articleIdentity":"rs-3180261","link":"https://doi.org/10.1038/s41598-024-57217-5","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2024-03-28 15:01:47","publishedOnDateReadable":"March 28th, 2024"},"versionCreatedAt":"2023-08-02 22:10:52","video":"","vorDoi":"10.1038/s41598-024-57217-5","vorDoiUrl":"https://doi.org/10.1038/s41598-024-57217-5","workflowStages":[]},"version":"v1","identity":"rs-3180261","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3180261","identity":"rs-3180261","version":["v1"]},"buildId":"J0_U0BvcaRcwD8yVFaRlm","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}