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.

[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.

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.

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.

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.

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.

The Impact of Heart Rate Response During 48-Hour Rewarming Phase of Therapeutic Hypothermia on Neurologic Outcomes in Out-of-Hospital Cardiac Arrest Patients.

OBJECTIVES: Bradycardia during therapeutic hypothermia has been reported to be a predictor of favorable neurologic outcomes in out-of-hospital cardiac arrests. However, bradycardia occurrence rate may be influenced by the target body temperature. During therapeutic hypothermia, as part of the normal physiologic response, heart rate decreases in the cooling phase and increases during the rewarming phase. We hypothesized that increased heart rate during the rewarming phase is another predictor of favorable neurologic outcomes. To address this hypothesis, the study aimed to examine the association between heart rate response during the rewarming phase and neurologic outcomes in patients having return of spontaneous circulation after out-of-hospital cardiac arrest. DESIGN: A secondary analysis of the Japanese Population-based Utstein style study with defibrillation and basic/advanced Life Support Education and implementation-Hypothermia registry, which was a multicenter prospective cohort study. SETTING: Fourteen hospitals throughout Japan. PATIENTS: Patients suffering from out-of-hospital cardiac arrest who received therapeutic hypothermia after the return of spontaneous circulation from 2005 to 2011. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: This study enrolled 452 out-of-hospital cardiac arrest patients, of which 354 were analyzed, and 80.2% survived to hospital discharge, of which 57.3% had a good neurologic outcome. Heart rate response was calculated using heart rate data recorded during therapeutic hypothermia in the abovementioned registry. Heart rate response in the rewarming phase (heart rate response-rewarming) was calculated as follows: (heart rate [post rewarming]-heart rate [pre rewarming])/heart rate (pre rewarming) × 100. The primary outcome was an unfavorable neurologic outcome at hospital discharge, that is, a Cerebral Performance Category of 3-5. Multivariable logistic regression analysis was performed to determine the association between heart rate response-rewarming and unfavorable neurologic outcomes. Multivariable logistic regression analysis showed that heart rate response-rewarming was independently associated with unfavorable outcomes (odds ratio [per 10% change], 0.86; 95% CI, 0.78-0.96; p = 0.004). CONCLUSIONS: Increased heart rate in the approximately 48-hour rewarming phase during therapeutic hypothermia was significantly associated with and was an independent predictor of favorable neurologic outcomes during out-of-hospital cardiac arrest.

Feasibility and Safety of Intravascular Temperature Management for Severe Heat Stroke: A Prospective Multicenter Pilot Study.

OBJECTIVES: Heat stroke is a life-threatening condition with high mortality and morbidity. Although several cooling methods have been reported, the feasibility and safety of treating heat stroke using intravascular temperature management are unclear. This study evaluated the efficacies of conventional treatment with or without intravascular temperature management for severe heat stroke. DESIGN: Prospective multicenter study. SETTING: Critical care and emergency medical centers at 10 tertiary hospitals. PATIENTS: Patients with severe heat stroke hospitalized during two summers. INTERVENTIONS: Conventional cooling with or without intravascular temperature management. MEASUREMENTS AND MAIN RESULTS: Cooling efficacy, Sequential Organ Failure Assessment score, occurrence rate of serious adverse events, and prognosis based on the modified Rankin Scale and Cerebral Performance Category. Patient outcomes were compared between five centers that were prospectively assigned to perform conventional cooling (control group: eight patients) and five centers that were assigned to perform conventional cooling plus intravascular temperature management (intravascular temperature management group: 13 patients), based on equipment availability. Despite their higher initial temperatures, all patients in the intravascular temperature management group reached the target temperature of 37°C within 24 hours, although only 50% of the patients in the control group reached 37°C (p < 0.01). The intravascular temperature management group also had a significant decrease in the Sequential Organ Failure Assessment score during the first 24 hours after admission (4.0 vs 1.5; p = 0.04). Furthermore, the intravascular temperature management group experienced fewer serious adverse events during their hospitalization, compared with the control group. The percentages of favorable outcomes at discharge and 30 days after admission were not statistically significant. CONCLUSIONS: The combination of intravascular temperature management and conventional cooling was safe and feasible for treating severe heat stroke. The results indicate that better temperature management may help prevent organ failure. A large randomized controlled trial is needed to validate our findings.

Mild decrease in heart rate during early phase of targeted temperature management following tachycardia on admission is associated with unfavorable neurological outcomes after severe traumatic brain injury: a post hoc analysis of a multicenter randomized controlled trial.

BACKGROUND: The association between isolated admission heart rate (HR) and prognosis has been discussed, but not that between gross HR change and neurological outcome in patients with severe traumatic brain injury (TBI). In the acute phase of severe TBI, HR is influenced by several factors (e.g., pain, sympathetic activation, hypovolemia, fever, body temperature). Therefore, admission HR and gross HR change should be examined in patients with TBI treated with a well-designed protocol, such as was done in the Brain Hypothermia (B-HYPO) Study. METHODS: This was a post hoc analysis of the B-HYPO Study, which was conducted as a prospective, multicenter, randomized controlled trial in patients with severe TBI receiving mild therapeutic hypothermia (MTH; 32.0 °C-34.0 °C) or fever control (35.5 °C-37.0 °C) in Japan. Patients with MTH were examined, and HR change (%HR) in the early MTH phase was calculated as follows: [admission HR - HR at day 1]/admission HR × 100. Patients were divided into six groups, using admission HR (< 80, 80-99, ≤ 100) and median of %HR; i.e., group (Admission HR < 80 and %HR ≥ 18.6); group (Admission HR < 80 and %HR < 18.6); group (Admission HR 80-99 and %HR ≥ 18.6); group (Admission HR 80-99 and %HR < 18.6); group (Admission HR ≥100 and %HR ≥ 18.6); and group (Admission HR ≥100 and %HR < 18.6). The primary outcome was an adjusted predicted probability of unfavorable neurological outcome at 6 months after TBI according to Glasgow Outcome Scale score, which is a measure of functional recovery and defined as severe disability, persistent vegetative state, and death. RESULTS: Overall, 79 patients with MTH (52.7% of the original trial) were examined; among these, unfavorable neurological outcomes were observed in 53.2%. Among all the groups, group (Admission HR ≥100 and %HR < 18.6) exhibited the highest proportion of unfavorable outcomes, and 82.3% of patients had an adjusted predicted probability of unfavorable outcomes, whereas those in group (Admission HR < 80 and %HR ≥ 18.6) developed only 22.8% (p = 0.04). CONCLUSIONS: Mild HR decrease during the early phase of targeted temperature management following tachycardia at admission can be associated with unfavorable neurological outcomes after severe TBI.

Blood Glucose Variability: A Strong Independent Predictor of Neurological Outcomes in Aneurysmal Subarachnoid Hemorrhage.

PURPOSE: In patients with aneurysmal subarachnoid hemorrhage (SAH), increased glucose variability (GV) is associated with increased mortality and cerebral infarction; however, there are no reports demonstrating an association between GV and neurological outcome. This study investigated whether GV had an independent effect on neurological outcomes in patients with SAH in the intensive care unit. MATERIALS AND METHODS: Consecutive adult patients hospitalized with SAH between January 1, 2009, and May 31, 2015 (N = 122) were retrospectively reviewed. Univariate/multivariate analyses were performed to identify independent predictors of poor neurological outcome. Patients were divided according to the mean glucose level (80-139 vs 140-200 mg/dL) and further subdivided using quartiles (Q) of the standard deviation (SD, representing variability) of the glucose level (Q1, Q2 + 3, and Q4). RESULTS: Unfavorable neurological outcomes occurred in 44.2% of the patients. On multiple regression analysis, age, Hunt and Kosnik grade, SD of glucose (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.02-1.17; P < .01), and minimum blood glucose level (OR, 0.95; 95% CI, 0.91-0.99; P < .01) were significantly associated with unfavorable neurological outcomes. Both groups (mean glucose levels: 80-139 and 140-200 mg/dL groups) had increasing unfavorable neurological outcomes with increasing SD of glucose (Q1, 15.0%; Q2 + 3, 40.0%; Q4, 52.4% and Q1, 44.4%; Q2 + 3, 50%; Q4, 88.9% in the 80-139 and 140-200 mg/dL groups, respectively). Patients with minimum glucose of <90 mg/dL comprised >50% of unfavorable neurological outcome. CONCLUSION: Increased GV was an independent predictor of unfavorable neurological outcomes in patients with SAH.

Critical Care Management Focused on Optimizing Brain Function After Cardiac Arrest.

The discussion of neurocritical care management in post-cardiac arrest syndrome (PCAS) has generally focused on target values used for targeted temperature management (TTM). There has been less attention paid to target values for systemic and cerebral parameters to minimize secondary brain damage in PCAS. And the neurologic indications for TTM to produce a favorable neurologic outcome remain to be determined. Critical care management of PCAS patients is fundamental and essential for both cardiologists and general intensivists to improve neurologic outcome, because definitive therapy of PCAS includes both special management of the cause of cardiac arrest, such as coronary intervention to ischemic heart disease, and intensive management of the results of cardiac arrest, such as ventilation strategies to avoid brain ischemia. We reviewed the literature and the latest research about the following issues and propose practical care recommendations. Issues are (1) prediction of TTM candidate on admission, (2) cerebral blood flow and metabolism and target value of them, (3) seizure management using continuous electroencephalography, (4) target value of hemodynamic stabilization and its method, (5) management and analysis of respiration, (6) sedation and its monitoring, (7) shivering control and its monitoring, and (8) glucose management. We hope to establish standards of neurocritical care to optimize brain function and produce a favorable neurologic outcome.

Prognostic factors of Streptococcus pneumoniae infection in adults.

OBJECTIVES: The mortality of severe sepsis has markedly decreased since the implementation of the Surviving Sepsis Campaign guidelines. The next logical step is to examine the necessity of individualized management guidelines for targeted therapy against specific bacteria. Streptococcus pneumoniae is the leading cause of community-acquired severe sepsis; however, little is known regarding the prognostic factors in adult patients with S pneumoniae sepsis. We aimed to identify prognostic factors in patients with S pneumoniae sepsis and to explore a subgroup of patients at high risk for death with detailed Sequential Organ Failure Assessment (SOFA) score analysis. METHODS: We retrospectively reviewed the records of patients with S pneumoniae infection treated between 1st January 2006 and 31st July 2012. We identified prognostic factors for 28-day mortality using univariate and multivariate logistic regression models. RESULTS: Of 171 patients (median age, 72 years) with S pneumoniae infection who were included in this study, the 28-day mortality was 17% (29/171). The SOFA score (odds ratio, 2.25; 95% confidence interval, 1.60-3.18; P < .001) and bacteremia (odds ratio, 19.0; 95% confidence interval, 4.06-90.20; P < .001) were identified as prognostic factors for the 28-day mortality. In a subgroup analysis with a cutoff value of the SOFA score determined by receiver operating characteristic analysis, patients with bacteremia and a SOFA score of at least 7 had a significantly higher mortality than did patients without bacteremia and a SOFA score lower than 7 (84% vs 0%, respectively). CONCLUSIONS: Bacteremia and a SOFA score at least 7 were independent prognostic factors of poor outcome in S pneumoniae sepsis.

d-Allose Attenuates Overexpression of Inflammatory Cytokines after Cerebral Ischemia/Reperfusion Injury in Gerbil.

BACKGROUND: The present study investigates the effects of d-allose, a rare sugar, on the inflammatory response after transient forebrain ischemia in the gerbil and whether it reduces oxidative stress (8-hydroxyl-2'-deoxyguanosine levels) and behavioral deficits. METHODS: Transient forebrain ischemia was induced by occlusion of the bilateral common carotid arteries for 5 minutes. d-Allose was intraperitoneally injected immediately after ischemia (400 mg/kg). Inflammatory cytokines and oxidative damage in the hippocampus and behavioral deficits were examined 3 days after ischemia. RESULTS: d-Allose administration reduced ischemia-induced cytokine production, oxidative stress, and behavioral deficits (motor and memory related). CONCLUSIONS: The present results suggest that d-allose reduces brain injury after transient global ischemia by suppressing inflammation as well as by inhibiting oxidative stress.

Effect of Admission Glasgow Coma Scale Motor Score on Neurological Outcome in Out-of-Hospital Cardiac Arrest Patients Receiving Therapeutic Hypothermia.

BACKGROUND: Because the initial (on admission) Glasgow Coma Scale (GCS) examination has not been fully evaluated in comatose survivors of cardiac arrest (CA) who receive therapeutic hypothermia (TH), the aim of the present study was to determine any association between the admission GCS motor score and neurologic outcomes in patients with out-of-hospital CA who receive TH. METHODS AND RESULTS: In the J-PULSE-HYPO study registry, patients with bystander-witnessed CA were eligible for inclusion. Patients were divided into 3 groups based on GCS motor score (1, 2-3, and 4-5) to assess various effects on neurologic outcome. Univariate and multivariate analyses were performed to identify independent predictors of good neurologic outcome at 90 days. Of 452 patients, 302 were enrolled. There was a significant difference among the 3 patient groups with regard to neurologic outcome at 90 days in the univariate analysis. Multiple logistic regression analyses showed that the GCS motor score on admission, age >65 years, bystander cardiopulmonary resuscitation, the time from collapse to return of spontaneous circulation, and pupil size <4 mm were independent predictors of a good neurologic outcome at 90 days in cases of CA (GCS motor score, 4-5: odds ratio, 8.18; 95% confidence interval: 1.90-60.28; P<0.01). CONCLUSIONS: GCS motor score is an independent predictor of good neurologic outcome at 90 days in patients sustaining out-of-hospital CA who receive TH.

Vitamin K2 for the reversal of warfarin-related coagulopathy.

The American Heart Association/American College of Cardiology Foundation recommends vitamin K1 for warfarin-related coagulopathy. In Japan, vitamin K2 is used more commonly for such purpose. The difference between vitamins K1 and K2 in reversing warfarin-related coagulopathy has not been discussed. Herein, we report a case that was reversed with vitamin K2; alterations in vitamins K1 and K2 levels and coagulation markers are also presented.

The impact of age on outcomes of elderly ED patients ventilated due to community acquired pneumonia.

OBJECTIVES: There is no consensus on whether mechanical ventilation should be initiated for advanced age with community-acquired pneumonia (CAP). This study investigated the effects of age on the outcomes of mechanical ventilation in the emergency department (ED) for advanced age with CAP. METHODS: We retrospectively investigated the medical records of advanced age (age, ≥65 years) with CAP who required mechanical ventilation in the ED of our hospital between January 2006 and December 2012. The patients were divided into 65 to 74, 75 to 84, and 85 years or older age groups. The following outcomes were measured: number of patients weaned from mechanical ventilation, in-hospital mortality, ventilator-free days, and intensive care unit days. Multiple logistic regression analysis was used to identify risk factors associated with mortality and weaning from mechanical ventilation. RESULTS: Seventy-one patients (mean age, 79.5 years) were included. The overall in-hospital mortality rate was 43.7%. No significant differences were observed among the 3 groups with regard to weaning from mechanical ventilation (P=.59), in-hospital mortality (P=.90), ventilator-free days (P=.83), or intensive care unit days (P=.12). Age was not significantly associated with weaning from mechanical ventilation or in-hospital mortality among advanced age. Diabetes mellitus was an independent factor for weaning from mechanical ventilation (P=.048) and was relatively associated with mortality (P=.051). CONCLUSIONS: Age, in itself, may not be a factor limiting the initiation of mechanical ventilation in the ED in advanced age with CAP. Further studies should determine appropriate indications for mechanical ventilation in the ED for these patients.

Successful management of heat stroke associated with multiple-organ dysfunction by active intravascular cooling.

Heat stroke is a life-threatening condition requiring immediate initiation of rapid and effective cooling. We report successful cooling with initial intravascular cooling use that rapidly achieved the target temperature with continued normothermia thereafter. A 39-year-old previously healthy man collapsed on a hot, humid day and presented with a disturbance of consciousness. On initial examination, Glasgow Coma Scale score was 6/15, and his body temperature was 40.7°C. He was therefore intubated, and fluid resuscitation was initiated. A Cool Line catheter (Asahi KASEI ZOLL Medical, Tokyo, Japan) was inserted, and aggressive cooling was started using the intravascular balloon-catheter system (The Thermogard XP system; Asahi KASEI ZOLL Medical) within 32 minutes of arrival. His core temperature reached 38.8°C after 17 minutes of intravascular cooling at an average cooling rate of 0.10°C/min. Further investigation revealed impaired liver function and renal failure. His hemodynamic condition was stabilized, and no vasoactive agents were administrated during hospitalization. The cooling catheter was removed on day 2 of admission, and no bleeding, infection, or thrombosis associated with catheter placement was observed. Blood and urine cultures remained negative. Extubation was performed on day 3, and he was discharged on day 5 without further complication or sequelae. It is essential in the treatment of heat stroke to cool as quickly as possible and to provide cardiovascular support. In patients with severe heat stroke and multiple-organ dysfunction, initial use of the active intravascular cooling technique is warranted for aggressive cooling.

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.

Effects of dual antiplatelet therapy (DAPT) compared to single antiplatelet therapy (SAPT) in patients with traumatic brain injury.

Japan is one of the world's most aging societies and the number of elderly patients taking antithrombotic drugs is increasing. In recent years, dual antiplatelet therapy (DAPT), in which two antiplatelet drugs are administered, has become common in anticipation of its high therapeutic efficacy. However, there are concerns about increased bleeding complications in use of DAPT. Therefore, the goal of this study was to investigate the effects of DAPT in patients with traumatic brain injury (TBI). A prospective, multicenter, observational study was conducted from December 2019 to May 2021 to examine the effects of antithrombotic drugs and reversal drugs in 721 elderly patients with TBI. In the current study, the effect of DAPT on TBI was examined in a secondary analysis. Among the registered patients, 132 patients taking antiplatelet drugs only were divided into those treated with single antiplatelet therapy (SAPT) (n=106) and those treated with DAPT (n=26) prior to TBI. Glasgow Coma Scale (GCS) on admission, pupillary findings, course during hospitalization, and outcome were compared in the two groups. A similar analysis was performed in patients with a mild GCS of 13-15 (n=95) and a moderate to severe GCS of 3-12 (n=37) on admission. The DAPT group had significantly more males (67.0 % vs. 96.2 %), a higher severity of illness on admission, and a higher frequency of brain herniation findings on head CT (21.7 % vs. 46.2 %), resulting in significantly higher mortality (12.3 % vs. 30.8 %). The only significant factor for mortality was severity on admission. The rate of DAPT was significantly higher in patients with a moderate to severe GCS on admission, and DAPT was the only significant factor related to severity on admission. These findings suggest that the severity of injury on admission influences the outcome six months after injury, and that patients with more severe TBI on admission are more likely to have been treated with DAPT compared to SAPT.