Review of Temperature Management in Traumatic Brain Injuries.

Therapeutic hypothermia (TH) for severe traumatic brain injury has seen restricted application due to the outcomes of randomized controlled trials (RCTs) conducted since 2000. In contrast with earlier RCTs, recent trials have implemented active normothermia management in control groups, ensuring comparable intensities of non-temperature-related therapeutic interventions, such as neurointensive care. This change in approach may be a contributing factor to the inability to establish the efficacy of TH. Currently, an active temperature management method using temperature control devices is termed "targeted temperature management (TTM)". One of the goals of TTM for severe traumatic brain injury is the regulation of increased intracranial pressure, employing TTM as a methodology for intracranial pressure management. Additionally, fever in traumatic brain injury has been acknowledged as contributing to poor prognosis, underscoring the importance of proactively preventing fever. TTM is also employed for the preemptive prevention of fever in severe traumatic brain injury. As an integral component of current neurointensive care, it is crucial to precisely delineate the targets of TTM and to potentially apply them in the treatment of severe traumatic brain injury.

The current status of reversal therapy in Japan for elderly patients with head injury treated with antithrombotic agents: A prospective multicenter observational study.

Background: Acute exacerbation of head injury in elderly patients due to use of antithrombotic agents has become a concern in countries with aging populations. Reversal agents are recommended for treatment, but its usage is unclear. Therefore, we conducted a prospective observational study in this patient population to monitor usage of reversal therapy. Methods: The subjects were 721 elderly patients aged ≥65 years old who were hospitalized in 15 centers from December 2019 to May 2021. Patients were divided into groups who did not receive antithrombotic agents (Group A), who received antithrombotic agents, but did not receive reversal therapy (Group B), and were treated with antithrombotic agents and reversal therapy (Group C). Age, gender, mechanism of injury, neurologic and imaging findings on admission, clinical course after admission and surgery, outcomes and complications were compared among these groups. Time from injury to reversal therapy was examined based on outcomes to investigate trends in the timing of administration of the reversal agent. Results: Acute exacerbation during the clinical course occurred in 9.8 %, 15.8 % and 31.0 % of cases in Groups A, B and C, respectively, and differed significantly among the groups. On head CT, the incidences of hematoma were 35.7 %, 36.5 % and 60.4 %, respectively, with this incidence being significantly higher in Group C; and the respective rates of craniotomy were 18.8 %, 14.0 % and 50.9 %, again with this rate being significantly higher in Group C. The good outcome and mortality rates were 57.1 %, 52.5 % and 35.8 %, and 14.5 %, 18.0 % and 24.5 %, respectively, and both were poorest in Group C. Times from injury to treatment with a reversal agent were significantly shorter in patients without compared to those with acute exacerbation (405.9 vs. 880.8 min) and in patients with favorable outcomes compared to those with unfavorable outcomes (261.9 vs. 543.4 min). Conclusion: Similarly to previous studies, the incidence of acute exacerbation was increased by use of antithrombotic agents. These results suggest that patients in Japan who require hematoma evacuation due to symptom exacerbation tend to be treated with reversal agents. Although it is difficult to assess the efficacy of reversal therapy from this study, earlier treatment with reversal agents before the occurrence of acute exacerbation may be useful to improve outcomes.

[Neurointensive Care:Targeted Temperature Management].

The neuroprotective effects of hypothermia therapy have been sufficiently demonstrated; however, the conditions under which it is considered effective have become limited. Recently, the term "temperature management therapy" has been more frequently used than "hypothermia therapy." In neurointensive care, in the acute phase of neurological disorders, not only lowering body temperature but also targeted temperature management according to each case is an important technique. In our facility, targeted temperature management is primarily used to control intracranial pressure and fever. It is important to clarify the purpose of temperature management and emphasize neurointensive care that minimizes secondary brain damage instead of focusing only on temperature control.

Potential Interaction Between Sepsis and Acute Respiratory Distress Syndrome and Effect on the 6-Month Clinical Outcomes: A Preliminary Secondary Analysis of a Prospective Observational Study.

BACKGROUND: This study aimed to investigate the effect of the potential interaction between sepsis and acute respiratory distress syndrome (ARDS) on the 6-month clinical outcomes. METHODS: This secondary analysis of a prospective multicenter observational study included patients who were expected to receive mechanical ventilation for more than 48 h. Patients were stratified based on the incidence of sepsis and further subdivided according to the presence of ARDS. The primary endpoints for patients whose follow-up information was available included mortality (n = 162) and the occurrence of PICS (n = 96) at six months. The diagnosis of PICS was based on any of the following criteria: (1) decrease ≥ 10 points in the physical component score of the 36-item Short Form (SF36) questionnaire; (2) decrease ≥ 10 points in the mental component score of the SF-36; or (3) decline in the Short Memory Questionnaire (SMQ) score and SMQ score < 40 at six months after ICU admission. We conducted multivariate logistic regression analyses to assess the effect of the potential interaction between ARDS and sepsis on the 6-month clinical outcomes. RESULTS: The mortality in the ARDS sub-group was higher than that in the non-ARDS subgroup [47% (7/15) versus 21% (18/85)] in the non-sepsis group. However, the mortality in the ARDS and non-ARDS subgroups was similar in the sepsis group. Multivariate logistic regression analyses revealed that ARDS was significantly associated with mortality in the non-sepsis group (adjusted OR: 5.25; 95% CI: 1.45-19.09; p = .012), but not in the sepsis group (P for interaction = .087). Multivariate logistic regression analyses showed ARDS was not associated with PICS occurrence in the non-sepsis and sepsis groups (P-value for the interaction = .039). CONCLUSIONS: This hypothesis-generating study suggested that the effect of ARDS on the 6-month outcomes depended on the presence or absence of sepsis. TRIAL REGISTRATION: Not applicable.

Association between time in range of relative normoglycemia and in-hospital mortality in critically ill patients: a single-center retrospective study.

The aim of this single-center retrospective study was to investigate the association between the time in range (TIR) of relative normoglycemia (RN) and in-hospital mortality. We defined RN as measured blood glucose in the range of 70-140% of A1C-derived average glucose and absolute normoglycemia (AN) as 70-140 mg/dL. We conducted multivariate logistic regression analyses to examine the association between TIR of RN > 80% or TIR of AN > 80% up to 72 h after ICU admission and in-hospital mortality (Model 1 and Model 2, respectively). The discrimination of the models was assessed using the area under the receiver operating characteristic curve (AUROC). Among 328 patients, 35 died in hospital (11%). Model 1 showed that TIR of RN > 80% was associated with reduced in-hospital mortality (adjusted OR 0.16; 95% CI 0.06-0.43; P < 0. 001); however, Model 2 showed that the TIR of AN > 80% was not. The AUROC of Model 1 was significantly higher than that of Model 2 (0.84 [95% CI 0.77-0.90] vs. 0.79 [0.70-0.87], P = 0.008).Our findings provide a foundation for further studies exploring individualized glycemic management in ICUs.

Endovascular Treatment for Posterior Communicating Artery Aneurysms with Oculomotor Nerve Palsy.

Objective: Coil embolization for the treatment of internal carotid artery-posterior communicating artery aneurysms (PComAAn) associated with oculomotor nerve palsy (ONP) remains controversial in terms of the therapeutic effect to improve ONP. Patients with PComAAn treated in our hospital were retrospectively analyzed to evaluate the effectiveness of coil embolization on ONP. Methods: Twenty-three patients who had coil embolization for PComAAn with ONP were included in the analysis. In the evaluation of postoperative outcome of ONP, complete resolution of all symptoms was considered as a total recovery. ONP with a few residual symptoms that are stable and not disabling was considered as a subtotal recovery and that with only a slight improvement as a partial recovery. Results: Preoperative ONP was complete palsy in 14 and partial palsy in nine cases. The mean maximum diameter of the aneurysms was 9.1 ± 3.5 mm (3-17 mm), and the mean time from the onset to treatment was 46.3 ± 98.4 days (0-300 days). The embolization state immediately after the procedure was complete occlusion in seven, neck remnant in eight, and body filling (BF) in eight cases. Total recovery was observed in nine, subtotal recovery in 11, and partial recovery in three cases. The mean time to any improvement in ONP was 6.0 ± 6.0 months (0.5-25 months). Comparing 20 cases with total plus subtotal recovery and three cases with partial recovery, five (25.0%) and three (100%) cases showed BF immediately after the procedure, respectively, which was statistically significant (P = 0.015). Conclusion: The analysis indicated that coil embolization for the treatment of PComAAn with ONP resulted in satisfactory recovery of ONP in 87% of the cases and the outcome of aneurysm embolization was related to improvement in ONP.

Case Series of Endovascular Therapy for Blood Blister-Like Aneurysm in Acute Phase.

Objective: Blood blister-like aneurysms (BBAs) of the internal carotid artery are highly challenging to treat due to their variable morphology and tendency for rupture and regrowth. Here, we report a single-institution experience of endovascular therapy (EVT) for BBA treatment. Methods: We retrospectively reviewed patients with ruptured BBA from 2006 to 2019. All patients in whom BBA was treated with EVT were included. Patients' aneurysmal characteristics, progression status, aneurysm occlusion on follow-up angiography, and modified Rankin Scale (mRS) score were recorded. Results: A total of 11 patients (5 women and 6 men) with the mean age of 46 ± 10 years were included in this study. As initial treatment, 9 patients were treated with stent-assisted coiling (SAC). Immediate angiographic results showed that 2 cases were body filling, 4 were neck remnant, and 3 were complete obliteration. Perioperative ischemic complications were not observed. On postoperative day 1, 2 patients suffered from rerupture, and their prognoses were poor. Retreatments were performed in 5 patients. Parent artery occlusion (PAO) was performed in 6 patients including 2 initial treatments and 4 retreatments. Symptomatic infarction developed in 2 patients. In 3 patients, bypass in combination with PAO was performed. Clinical data revealed discharge mRS scores of 0-2 and 3-6 in 4 and 7 patients, respectively. Conclusion: SAC is effective for the management of BBA. Careful follow-up and response are necessary after treatment with SAC.

Temporal and spatial changes in reactive astrogliosis examined by 18F-THK5351 positron emission tomography in a patient with severe traumatic brain injury.

BACKGROUND: The positron emission tomography (PET) radioligand 18F-THK5351 is now used to evaluate monoamine oxidase B expression in the reactive astrogliosis seen in various central nervous diseases. Traumatic brain injury (TBI) is known to induce reactive astrogliosis in the lesion site. This is a first report to examine the spatial and temporal changes in reactive astrogliosis as evaluated by 18F-THK5351 after a severe TBI. CASE PRESENTATION: A 27-year-old man suffering from a severe TBI with multiple brain contusions was examined using 18F-THK5351 PET/CT in the subacute and chronic phases after the injury. The first PET scan, performed 46 days after the TBI, showed intense uptake of 18F-THK5351 in and around the brain contusions. The second PET scan, performed 271 days after the TBI, showed reduced uptake of 18F-THK5351 at the original sites of the brain contusions and increased uptakes in the white matter surrounding the contusions and the corpus callosum. The patient exhibited sustained improvement of neuropsychological impairment between the two PET examinations and remarkable recovery from the severe TBI. CONCLUSIONS: There were evident temporal and spatial changes in 18F-THK5351 uptake in the traumatized brain between the two PET examinations. These changes may have been related to the remarkable neurological recovery in this patient. The degree and distribution of reactive astrogliosis detected by 18F-THK5351 PET may be useful in assessing pathophysiology and predicting prognosis in TBI patients.

Neurological outcomes associated with prehospital advanced airway management in patients with out-of-hospital cardiac arrest due to foreign body airway obstruction.

OBJECTIVES: Several studies have examined the association between advanced airway management (AAM) and survival for arrest that is non-shockable, noncardiac in origin, or due to suffocation; however, the efficacy of prehospital AAM compared with no AAM following foreign body removal by emergency medical services (EMS) has not been examined. We aimed to compare neurological outcomes in patients after out-of-hospital cardiac arrest (OHCA) due to foreign body airway obstruction (FBAO) managed with and without AAM after foreign body removal. METHODS: This retrospective observational cohort study used all emergency transportation data of Japan and the All-Japan Utstein Registry. We included patients with OHCA aged ≥18 years undergoing resuscitation and removal of airway foreign bodies by EMS from January 2015 to December 2017. The exposure of interest was prehospital AAM by EMS after foreign body removal, and the primary outcome was a favorable neurological outcome at hospital discharge (i.e., a cerebral performance category of 1-2). RESULTS: Overall, 329,098 adults had OHCAs and 23,060 had foreign bodies removed from their airways; 3681 adult patients met our eligibility criteria and were divided as: AAM (2045) and non-AAM (1636) groups. Propensity score matching resulted in 1210 matched pairs with balanced baseline characteristics between the groups. The rate of favorable neurological outcome was significantly lower in the AAM group than in the non-AAM group (OR 0.34, 95% CI 0.19-0.62). However, survival was not significantly different between the two groups (OR 1.08, 95% CI 0.84-1.37). CONCLUSIONS: We have not demonstrated the benefit of AAM for patients with OHCA due to FBAO. Further study will be required to confirm the efficacy of AAM for those patients.

Association between physical restraint requirement and unfavorable neurologic outcomes in subarachnoid hemorrhage.

BACKGROUND: Physical restraint has been commonly indicated to patients with brain dysfunction in neurocritical care. The effect of physical restraints on outcomes of critically ill adults remains controversial as no randomized controlled trials have compared its safety and efficacy, and the association between physical restraint requirement and neurological outcome in patients with subarachnoid hemorrhage (SAH) has not been fully examined. The aim of this study was to examine the association between physical restraint requirement and neurological outcomes in patients with SAH. METHODS: A single-center, retrospective study was conducted on patients with acute phase SAH treated for > 72 h in the intensive care unit from 2014 to 2020. Patients were divided into three groups based on the amount of time required for physical restraint during the first 24-72 h after admission: no, intermittent, and continuous use of physical restraint. Unfavorable neurologic outcome, assessed using the modified Rankin scale upon hospital discharge, has been considered as primary end point. RESULTS: Overall, 101 patients were included in the study, with 52 patients (51.5%) having unfavorable neurological outcomes. Among them, 46 patients (45.5%) did not use physical restraint, and 55 (54.5%) patients used physical restraint during the first 24-72 h after admission: 26 (25.7%) intermittent and 29 (28.7%) continuous. Multivariable logistic regression analysis showed that continuous use of physical restraint during the first 24-72 h after admission was significantly associated with unfavorable neurological outcomes in patients with SAH (odds ratio, 3.54; 95% confidence interval, 1.05-13.06; p = 0.042) compared with no physical restraint. CONCLUSIONS: Continuous use of physical restraint during the first 24-72 h after admission was more significantly associated with unfavorable neurological outcomes than no physical restraint among patients with SAH during the acute phase.

Hospital-level intracranial pressure monitoring utilization and functional outcome in severe traumatic brain injury: a post hoc analysis of prospective multicenter observational study.

BACKGROUND: Several observational studies have shown that hospital-level intracranial pressure (ICP) monitoring utilization varies considerably in patients with severe traumatic brain injury (TBI). However, the relationship between hospital-level ICP monitoring utilization and clinical functional outcomes is unknown. This study examined whether patients with severe TBI treated at hospitals with high ICP monitoring utilization have better functional outcomes. METHODS: A post hoc analysis of the data from a prospective multicenter cohort study in Japan was undertaken, and included severe TBI patients (Glasgow Come Scale score ≤ 8). The primary exposure was hospital-level ICP monitoring utilization. Patients treated at hospitals with more than 80% ICP monitoring utilization were assigned to a high group and the others to a low group. The primary endpoint was a favorable functional outcome at 6 months after injury, defined as a Glasgow Outcome Scale score of good recovery or moderate disability. We conducted multiple logistic regression analyses adjusted for potential confounders. RESULTS: Of the 427 included patients, 60 were assigned to the high group and 367 to the low group. Multiple logistic regression analysis revealed that patients in the high group had significantly better functional outcome (adjusted odds ratio [OR]: 2.36; 95% confidence interval [CI]: 1.17-4.76; p = 0.016). Multiple logistic regression analysis adjusted for additional confounders supported this result (adjusted OR: 2.30; 95% CI: 1.07-4.92; p = 0.033). CONCLUSION: Treatment at hospitals with high ICP monitoring utilization for severe TBI patients could be associated with better functional outcome.

High early phase hemoglobin level is associated with favorable neurological outcome in patients with severe traumatic brain injury.

BACKGROUND: The appropriate hemoglobin (Hb) level threshold for the early phase (i.e. from Emergency Department to ICU admission) in patients with severe traumatic brain injury (TBI) is still unknown. Therefore, we aimed to examine the association between Hb levels during the early phase and neurological outcomes in patients with severe TBI using data from the Brain Hypothermia (B-HYPO) Study Group. METHODS: We performed a post-hoc analysis of the B-HYPO study (a prospective, multicenter, randomized controlled trial on patients with severe TBI who received either mild therapeutic hypothermia [MTH; 32.0 °C-34.0 °C] or fever control [35.5 °C-37.0 °C]). We calculated Hb levels during early phase by the formula: (admission Hb + Hb on day 1) / 2. The primary outcome was the association between during early phase Hb levels and 6-month neurological outcome after the TBI based on the Glasgow Outcome Scale scores (a measure of functional recovery defined as moderate disability or good recovery). RESULTS: We reviewed data from 130 patients and found favorable neurological outcomes in 48.5% of them. We found significant differences between the favorable and unfavorable neurological outcome groups in terms of their Hb levels on admission and on day 1. But, we found no Hb level differences after day 3 (including 1 day after rewarming). Our multivariable analysis showed that Hb levels during early phase were significantly associated with favorable neurological outcomes (odds ratio, 1.387; 95% confidence interval, 1.057-1.858; P = 0.018). CONCLUSIONS: High early phase Hb levels are associated with favorable neurological outcomes after severe TBI.

The association between neuromuscular blockade use during target temperature management and neurological outcomes.

BACKGROUND: To date, no study has comprehensively analyzed the association between neuromuscular blockade (NMB) during target temperature management (TTM) and the neurological outcomes after out-of-hospital cardiac arrest (OHCA) using a multicenter dataset. We aimed to examine the association between NMB during TTM after cardiac arrest and neurological outcomes after OHCA. METHODS: This study was a secondary analysis of the Japanese Population-based Utstein-style study with defibrillation and basic/advanced Life Support Education and implementation-Hypothermia (J-PULSE-HYPO) study registry. The exposure of the current study was the use of NMB during TTM. The primary outcome was favorable neurological outcome, i.e., a cerebral performance category of 1-2, at hospital discharge. RESULTS: Of the 452 patients with OHCA enrolled in the J-PULSE-HYPO study, 431 were analyzed. NMB was used in 353 patients (81.9%). Multivariable logistic regression analysis revealed that NMB use was not independently associated with favorable outcomes [odds ratio (OR), 0.96; 95% confidence interval (CI), 0.42-2.18; p = .918)] or survival at discharge (OR, 0.83; 95% CI, 0.31-2.02; p = .688). After adjusting the covariates, the predicted probabilities did not reveal significant differences between NMB use and non-NMB use in the respective mean (95% CI) values for favorable neurological outcomes [53.6 (50.2-57.0) % vs. 58.0 (50.4-65.6) %, p = .304], and survival rates [77.1 (74.7-79.5) % vs. 75.8 (70.5-81.0) %, p = .647]. CONCLUSIONS: The NMB use during TTM was not associated with favorable neurological outcomes and survival rate in patients with OHCA.

Uterine sarcoma with posterior reversible encephalopathy syndrome associated with pazopanib.

WHAT IS KNOWN AND OBJECTIVE: Our objective is to report on a case of posterior reversible encephalopathy syndrome associated with pazopanib. CASE DESCRIPTION: A 64-year-old patient with uterine sarcoma developed PRES 3 days after pazopanib was initiated. After the discontinuation of pazopanib, the symptoms of PRES improved. WHAT IS NEW AND CONCLUSION: The first report worldwide to describe a patient with uterine sarcoma experiencing PRES caused by pazopanib. Patients with uterine sarcoma may experience PRES, even in the early phase of pazopanib therapy.

Association between rewarming duration and neurological outcome in out-of-hospital cardiac arrest patients receiving therapeutic hypothermia.

AIM: The European Resuscitation Council guidelines recommend a slow rate of rewarming of 0.25 °C/h-0.5 °C/h for out-of-hospital cardiac arrest (OHCA) patients receiving therapeutic hypothermia (TH). Conversely, a very slow rewarming of 1 °C/day is generally applied in Japan. The rewarming duration ranged from less than 24 h up to more than 50 h. No randomized control trials have examined the optimal rewarming speed for TH in OHCA patients. Therefore, we examined the association between the rewarming duration and neurological outcomes in OHCA patients who received TH. METHODS: This study was a secondary analysis of the Japanese Population-based Utstein-style study with defibrillation and basic/advanced Life Support Education and implementation-Hypothermia (J-PULSE-HYPO) study registry, a multicenter prospective cohort study. Patients suffering from OHCA who received TH (target temperature, 34 °C) after the return of spontaneous circulation from 2005 to 2011 in 14 hospitals throughout Japan were enrolled. The rewarming duration was defined as the time from the beginning of rewarming at a target temperature of 34 °C until reaching 36 °C. The primary outcome was an unfavorable neurological outcome at hospital discharge, i.e., a cerebral performance category of 3-5. RESULTS: The J-PULSE-HYPO study enrolled 452 OHCA patients. Of these, 328 were analyzed; 79.9% survived to hospital discharge, of which 56.4% had a favorable neurological outcome. Multivariable logistic regression analysis revealed that the rewarming duration was independently associated with unfavorable neurological outcomes [odds ratio (per 5 h), 0.89; 95% confidence interval, 0.79-0.99; p =  0.032]. CONCLUSION: A longer rewarming duration was significantly associated with and was an independent predictor of favorable neurological outcomes in OHCA patients who received TH.

Targeted temperature management guided by the severity of hyperlactatemia for out-of-hospital cardiac arrest patients: a post hoc analysis of a nationwide, multicenter prospective registry.

BACKGROUND: The International Liaison Committee on Resuscitation guidelines recommend target temperature management (TTM) between 32 and 36 °C for patients after out-of-hospital cardiac arrest, but did not indicate patient-specific temperatures. The association of serum lactate concentration and neurological outcome in out-of-hospital cardiac arrest patient has been reported. The study aim was to investigate the benefit of 32-34 °C in patients with various degrees of hyperlactatemia compared to 35-36 °C. METHODS: This study was a post hoc analysis of the Japanese Association for Acute Medicine out-of-hospital cardiac arrest registry between June 2014 and December 2015. Patients with complete targeted temperature management and lactate data were eligible. Patients were stratified to mild (< 7 mmol/l), moderate (< 12 mmol/l), or severe (≥ 12 mmol/l) hyperlactatemia group based on lactate concentration after return of spontaneous circulation. They were subdivided into 32-34 °C or 35-36 °C groups. The primary endpoint was an adjusted predicted probability of 30-day favorable neurological outcome, defined as a cerebral performance category score of 1 or 2. RESULT: Of 435 patients, 139 had mild, 182 had moderate, and 114 had severe hyperlactatemia. One hundred and eight (78%) with mild, 128 with moderate (70%), and 83 with severe hyperlactatemia (73%) received TTM at 32-34 °C. The adjusted predicted probability of a 30-day favorable neurological outcome following severe hyperlactatemia was significantly greater with 32-34 °C (27.4%, 95% confidence interval: 22.0-32.8%) than 35-36 °C (12.4%, 95% CI 3.5-21.2%; p = 0.005). The differences in outcomes in those with mild and moderate hyperlactatemia were not significant. CONCLUSIONS: In OHCA patients with severe hyperlactatemia, the adjusted predicted probability of 30-day favorable neurological outcome was greater with TTM at 32-34 °C than with TTM at 35-36 °C. Further evaluation is needed to determine whether TTM at 32-34 °C can improve neurological outcomes in patients with severe hyperlactatemia after out-of-hospital cardiac arrest.

Histidine-rich Glycoprotein Could Be an Early Predictor of Vasospasm after Aneurysmal Subarachnoid Hemorrhage.

Cerebral vasospasm (CVS) is a major contributor to the high morbidity and mortality of aneurysmal subarachnoid hemorrhage (aSAH) patients. We measured histidine-rich glycoprotein (HRG), a new biomarker of aSAH, in cerebrospinal fluid (CSF) to investigate whether HRG might be an early predictor of CVS. A total of seven controls and 14 aSAH patients (8 males, 6 females aged 53.4±15.4 years) were enrolled, and serial CSF and serum samples were taken. We allocated these samples to three phases (T1-T3) and measured HRG, interleukin (IL)-6, fibrinopeptide A (FpA), and 8-hydroxy-2'-deoxyguanosine (8OHdG) in the CSF, and the HRG in serum. We also examined the release of HRG in rat blood incubated in artificial CSF. In contrast to the other biomarkers examined, the change in the CSF HRG concentration was significantly different between the nonspasm and spasm groups (p<0.01). The rat blood/CSF model revealed a time course similar to that of the human CSF samples in the non-spasm group. HRG thus appears to have the potential to become an early predictor of CVS. In addition, the interaction of HRG with IL-6, FpA, and 8OHdG may form the pathology of CVS.

Early Hyperoxia in The Intensive Care Unit is Significantly Associated With Unfavorable Neurological Outcomes in Patients With Mild-to-Moderate Aneurysmal Subarachnoid Hemorrhage.

INTRODUCTION: Although oxygen administration is fundamental in the management of aneurysmal subarachnoid hemorrhage (SAH) patients in the acute stage, hyperoxia has harmful effects. The effects of hyperoxia on neurological outcomes in SAH patients are unclear. We aimed to examine the association of hyperoxia during the first 24 h in the intensive care unit (ICU) with unfavorable neurological outcomes in SAH patients. METHODS: We retrospectively selected consecutive adult patients admitted to ICU for SAH between January 2009 and April 2018. We defined normoxia during the first 24 h in ICU as PaO2 of 60 mm Hg to 120 mm Hg, mild hyperoxia as PaO2 of 121 mm Hg to 200 mm Hg, moderate hyperoxia as PaO2 of 201 mm Hg to 300 mm Hg, and severe hyperoxia as PaO2 of >300 mm Hg. Univariate and multivariate analyses were performed to examine the association between hyperoxia during the first 24 h in ICU and unfavorable neurological outcomes (i.e., modified Rankin scale score of 3-6 at hospital discharge). RESULTS: Among 196 SAH patients, 90 had unfavorable neurological outcomes. Hyperoxia was observed in 93.4% of patients. No significant association was observed between unfavorable neurological outcomes and hyperoxia in overall patients. However, we found that early hyperoxia in ICU was significantly associated with unfavorable neurological outcomes in SAH patients with Hunt and Kosnik (H&K) grades I to III (Relative risk, 1.84; 95% confidence interval, 1.10-2.94; P = 0.02). CONCLUSIONS: Early hyperoxia was not associated with unfavorable neurological outcomes in overall SAH patients, but it was associated with unfavorable neurological outcomes in those with H&K grades I to III.

Association of abnormal carbon dioxide levels with poor neurological outcomes in aneurysmal subarachnoid hemorrhage: a retrospective observational study.

BACKGROUND: In patients with aneurysmal subarachnoid hemorrhage (SAH), an association between hypocapnia and poor clinical outcomes has been reported. However, the optimal arterial carbon dioxide tension (PaCO2) remains unknown. The present retrospective study aimed to examine the association of abnormal PaCO2 levels with neurological outcomes and investigate the optimal target PaCO2 level in patients with SAH. METHODS: We retrospectively selected consecutive adult patients hospitalized in the intensive care unit (ICU) for SAH between January 2009 and April 2017. Univariate and multivariate analyses were performed to identify the independent predictors of unfavorable neurological outcomes (i.e., modified Rankin scale score of 3-6 on hospital discharge). RESULTS: Among 158 patients with SAH, 73 had unfavorable neurological outcomes. During the first 2 weeks in the ICU, the median number of PaCO2 measurements per patient was 43. The factors significantly associated with unfavorable neurological outcomes were age, Hunt and Kosnik grade, maximum lactate levels during the first 24 h, and maximum (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.03-1.21; p < 0.01) and minimum PaCO2 levels (OR, 0.81; 95% CI, 0.72-0.92; p < 0.01). Receiver operating characteristic curve analysis revealed that the cutoff range of PaCO2 was 30.2-48.3 mmHg. Unfavorable neurological outcomes were noted in 78.8% of patients with PaCO2 levels outside this range and in 22.8% of patients with PaCO2 levels within this range. CONCLUSIONS: Both the maximum and minimum PaCO2 levels during ICU management in patients with SAH were significantly associated with unfavorable neurological outcomes. Further prospective studies are required to validate our findings and explore their clinical implications. Our findings may provide a scientific rationale for these future prospective studies.