Effect of glucagon like peptide-1 receptor agonist exenatide, used as an intracranial pressure lowering agent, on cognition in Idiopathic Intracranial Hypertension.

BACKGROUND: Cognitive function can be affected in conditions with raised intracranial pressure (ICP) such as idiopathic intracranial hypertension (IIH). Drugs used off label to treat raised ICP also have cognitive side effects, underscoring the unmet need for effective therapeutics which reduce ICP without worsening cognition. The Glucagon Like Peptide-1 (GLP-1) receptor agonist, exenatide, has been shown to significantly reduce ICP in IIH, therefore this study aimed to determine the effects of exenatide on cognition in IIH. METHODS: This was an exploratory study of the IIH:Pressure trial (ISTCRN 12678718). Women with IIH and telemetric ICP monitors (n = 15) were treated with exenatide (n = 7) or placebo (n = 8) for 12 weeks. Cognitive function was tested using the National Institute of Health Toolbox Cognitive Battery at baseline and 12 weeks. RESULTS: Cognitive performance was impaired in fluid intelligence ((T-score of 50 = population mean), mean (SD) 37.20 (9.87)), attention (33.93 (7.15)) and executive function (38.07 (14.61)). After 12-weeks there was no evidence that exenatide compromised cognition (no differences between exenatide and placebo). Cognition improved in exenatide treated patients in fluid intelligence (baseline 38.4 (8.2), 12 weeks 52.9 (6.6), p = 0.0005), processing speed (baseline 43.7 (9.4), 12 weeks 58.4 (10.4), p = 0.0058) and episodic memory (baseline 49.4 (5.3), 12 weeks 62.1 (13.2), p = 0.0315). CONCLUSIONS: In patients with raised ICP due to IIH, exenatide, a drug emerging as an ICP lowering agent, does not adversely impact cognition. This is encouraging and has potential to be relevant when considering prescribing choices to lower ICP.

Blood product resuscitation mitigates the effects of aeromedical evacuation after polytrauma.

BACKGROUND: The combined injury of traumatic brain injury and hemorrhagic shock has been shown to worsen coagulopathy and systemic inflammation, thereby increasing posttraumatic morbidity and mortality. Aeromedical evacuation to definitive care may exacerbate postinjury morbidity because of the inherent hypobaric hypoxic environment. We hypothesized that blood product resuscitation may mitigate the adverse physiologic effects of postinjury flight. METHODS: An established porcine model of controlled cortical injury was used to induce traumatic brain injury. Intracerebral monitors were placed to record intracranial pressure, brain tissue oxygenation, and cerebral perfusion. Each of the 42 pigs was hemorrhaged to a goal mean arterial pressure of 40 ± 5 mm Hg for 1 hour. Pigs were grouped according to resuscitation strategy used-Lactated Ringer's (LR) or shed whole blood (WB)-then placed in an altitude chamber for 2 hours at ground, 8,000 ft, or 22,000 ft, and then observed for 4 hours. Hourly blood samples were analyzed for proinflammatory cytokines and lactate. Internal jugular vein blood flow was monitored continuously for microbubble formation with altitude changes. RESULTS: Cerebral perfusion, tissue oxygenation, and intracranial pressure were unchanged among the six study groups. Venous microbubbles were not observed even with differing altitude or resuscitation strategy. Serum lactate levels from hour 2 of flight to the end of observation were significantly elevated in 22,000 + LR compared with 8,000 + LR and 22,000 + WB. Serum IL-6 levels were significantly elevated in 22,000 + LR compared with 22,000 + WB, 8,000 + LR and ground+LR at hour 1 of observation. Serum tumor necrosis factor-α was significantly elevated at hour 2 of flight in 8,000 + LR versus ground+LR, and in 22,000 + LR vs. 22,000 + WB at hour 1 of observation. Serum IL-1ß was significantly elevated hour 1 of flight between 8,000 + LR and ground+LR. CONCLUSION: Crystalloid resuscitation during aeromedical transport may cause a prolonged lactic acidosis and proinflammatory response that can predispose multiple-injury patients to secondary cellular injury. This physiologic insult may be prevented by using blood product resuscitation strategies.

Non-traumatic pediatric intracranial hypertension: key points for different etiologies, diagnosis, and treatment.

Intracranial hypertension can be an acute life-threatening event or slowly deteriorating condition, leading to a gradual loss of neurological function. The diagnosis should be taken in a timely fashioned process, which mandates expedite measures to save brain function and sometimes life. An optimal management strategy is selected according to the causative etiology with a core treatment paradigm that can be utilized in various etiologies. Distinct etiologies are intracranial bleeds caused by traumatic brain injury, spontaneous intracranial hemorrhage (e.g., neonatal intraventricular hemorrhage), or the rare pediatric hemorrhagic stroke. The other primary pediatric etiologies for elevated intracranial pressure are intracranial mass (e.g., brain tumor) and hydrocephalus related. Other unique etiologies in the pediatric population are related to congenital diseases, infectious diseases, metabolic or endocrine crisis, and idiopathic intracranial pressure. One of the main goals of treatment is to alleviate the growing pressure and prevent the secondary injury to brain parenchyma due to inadequate blood perfusion and eventually inadequate parenchymal oxygenation and metabolic state. Previous literature discussed essential characteristics of the treatment paradigm derived mainly from pediatric brain traumatic injuries' treatment methodology. Yet, many of these etiologies are not related to trauma; thus, the general treatment methodology must be tailored carefully for each patient. This review focuses on the different possible non-traumatic etiologies that can lead to intracranial hypertension with the relevant modification of each etiology's treatment paradigm based on the current literature.

Cranial Suture Regeneration Mitigates Skull and Neurocognitive Defects in Craniosynostosis.

Craniosynostosis results from premature fusion of the cranial suture(s), which contain mesenchymal stem cells (MSCs) that are crucial for calvarial expansion in coordination with brain growth. Infants with craniosynostosis have skull dysmorphology, increased intracranial pressure, and complications such as neurocognitive impairment that compromise quality of life. Animal models recapitulating these phenotypes are lacking, hampering development of urgently needed innovative therapies. Here, we show that Twist1+/- mice with craniosynostosis have increased intracranial pressure and neurocognitive behavioral abnormalities, recapitulating features of human Saethre-Chotzen syndrome. Using a biodegradable material combined with MSCs, we successfully regenerated a functional cranial suture that corrects skull deformity, normalizes intracranial pressure, and rescues neurocognitive behavior deficits. The regenerated suture creates a niche into which endogenous MSCs migrated, sustaining calvarial bone homeostasis and repair. MSC-based cranial suture regeneration offers a paradigm shift in treatment to reverse skull and neurocognitive abnormalities in this devastating disease.

Real-time intracranial pressure monitoring during high-dose methotrexate treatment for primary central nervous system lymphoma.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is an aggressive non-Hodgkin lymphoma with exclusive central nervous system (CNS) and/or ocular involvement. Increased intracranial pressure (ICP) from cerebral edema can commonly presents secondary to the mass effect of PCNSL. Methotrexate-based induction chemotherapy is the gold standard for treatment, however, several neurotoxic complications have been associated with high-dose methotrexate (HD-MTX) treatment. Tumor lysis and other biochemical disruptions following administration of HD-MTX are postulated to increase cerebral edema and ICP in predisposed patients, therefore, in the setting of ring-enhancing lesions with significant mass effect, monitoring of ICP to prevent cerebral herniation may be necessary. PRESENTATION OF CASE: We present the case of a patient with diffuse cerebral edema secondary to PCNSL, who was treated with methotrexate-based induction chemotherapy and underwent real-time ICP monitoring to allow for early recognition, and management with aggressive medical therapy to prevent worsening cerebral edema and potential fatal herniation. DISCUSSION AND CONCLUSIONS: Treatment of patients with high tumor burden PCNSL can prove to be challenging, particularly at the time of initiation of methotrexate based induction chemotherapy in the setting of impending cerebral herniation, as in the case presented. Close monitoring of the patient's ICP proved advantageous in rapidly recognizing, and successfully treating elevations in ICP that could have worsened mass effect and lead to fatal herniation.

Effects of propofol on intracranial pressure and prognosis in patients with severe brain diseases undergoing endotracheal suctioning.

BACKGROUND: To investigate whether the administration of intravenous propofol before endotracheal suctioning (ES) in patients with severe brain disease can reduce the sputum suction response, improve prognosis, and accelerate recovery. METHODS: A total of 208 severe brain disease patients after craniocerebral surgery were enrolled in the study. The subjects were randomly assigned to the experimental group (n = 104) and the control group (n = 104). The experimental group was given intravenous propofol (10 ml propofol with 1 ml 2% lidocaine), 0.5-1 mg/kg, before ES, while the control group was subjected to ES only. Changes in vital signs, sputum suction effect, the fluctuation range of intracranial pressure (ICP) before and after ES, choking cough response, short-term complications, length of stay, and hospitalization cost were evaluated. Additionally, the Glasgow Outcome Scale (GOS) prognosis score was obtained at 6 months after the operation. RESULTS: At the baseline, the characteristics of the two groups were comparable (P > 0.05). The increase of systolic blood pressure after ES was higher in the control group than in the experimental group (P < 0.05). The average peak value of ICP in the experimental group during the suctioning (15.57 ± 12.31 mmHg) was lower than in the control group (18.24 ± 8.99 mmHg; P < 0.05). The percentage of patients experiencing cough reaction- during suctioning in the experimental group was lower than in the control group (P < 0.05), and the fluctuation range of ICP was increased (P < 0.0001). The effect of ES was achieved in both groups. The incidence of short-term complications in the two groups was comparable (P > 0.05). At 6 months after the surgery, the GOS scores were significantly higher in the experimental than in the control group (4-5 points, 51.54% vs. 32.64%; 1-3 points, 48.46% vs. 67.36%; P < 0.05). There was no significant difference in the length of stay and hospitalization cost between the two groups. CONCLUSIONS: Propofol sedation before ES could reduce choking cough response and intracranial hypertension response. The use of propofol was safe and improved the long-term prognosis. The study was registered in the Chinese Clinical Trial Registry on May 16, 2015 (ChiCTR-IOR-15006441).

The neuroprotective effect of quetiapine in critically ill traumatic brain injury patients.

INTRODUCTION: Quetiapine is an atypical antipsychotic commonly used in critical care. Cellular and animal models demonstrated its novel anti-inflammatory properties in traumatic brain injury (TBI). Our study aimed to assess the effect of quetiapine on outcomes in critically ill TBI patients. We hypothesize that quetiapine improves neurological outcomes. METHODS: The Multiparameter Intelligent Monitoring in Intensive Care database was queried, and all adult (age, ≥18 years) isolated TBI patients (extracranial Abbreviated Injury Scale, < 2) admitted to the intensive care unit for a period of >48 hours. Patients were stratified into quetiapine (+) and no-quetiapine (-) groups. Propensity score matching was performed (1:2 ratio). Outcome measures were intensive care unit length of stay, discharge Glasgow Coma Scale (GCS), and mortality. A subanalysis was performed for patients who underwent intracranial pressure (ICP) monitoring to ascertain the effect of quetiapine dose on ICP, and cerebral perfusion pressure (CPP). Survival curves and regression analyses were performed. RESULTS: A matched cohort of (quetiapine, 116 vs. no-quetiapine, 232) patients was obtained. Mean ± SD age was 65 ± 21 years, median head Abbreviated Injury Scale was 3 (3-4), and median GCS was 10 (9-16). The median quetiapine dose given was 50 (25-125) mg. Patients who received quetiapine had lower mortality (17.2% vs. 27.6%; p = 0.03) and a higher median GCS at discharge (12 [11-14] vs. 11 [10-13]; p < 0.04) but no difference in intensive care unit length of stay (4.1 days vs. 4.7 days; p = 0.75) or discharge to skilled nursing facility (34.5% vs. 31.9%; p = 0.63). On subanalysis of patients who received quetiapine, 40% had ICP monitoring. Higher doses of quetiapine were independently associated with progressively lower ICP (ß = -0.022 mm Hg/mg of quetiapine; p = 0.01) and higher CPP (ß = 0.031 mm Hg/mg quetiapine; p = 0.01). CONCLUSION: Quetiapine may decrease mortality and improve neurological outcomes in critically ill TBI patients. It has a dose-dependent effect to decrease ICP and increase CPP. Quetiapine may be a potential therapeutic modality in critically ill TBI patients, but further studies are required to explore these mechanisms. LEVEL OF EVIDENCE: Systematic Review, level III.

Basic Fibroblast Growth Factor (bFGF) Protects the Blood-Brain Barrier by Binding of FGFR1 and Activating the ERK Signaling Pathway After Intra-Abdominal Hypertension and Traumatic Brain Injury.

BACKGROUND Intra-abdominal hypertension (IAH) is associated with high morbidity and mortality. IAH leads to intra-abdominal tissue damage and causes dysfunction in distal organs such as the brain. The effect of a combined injury due to IAH and traumatic brain injury (TBI) on the integrity of the blood-brain barrier (BBB) has not been investigated. MATERIAL AND METHODS Intracranial pressure (ICP) monitoring, brain water content, EB permeability detection, immunofluorescence staining, real-time PCR, and Western blot analysis were used to examine the effects of IAH and TBI on the BBB in rats, and to characterize the protective effects of basic fibroblast growth factor (bFGF) on combined injury-induced BBB damage. RESULTS Combined injury from IAH and TBI to the BBB resulted in brain edema and increased intracranial pressure. The effects of bFGF on alleviating the rat BBB injuries were determined, indicating that bFGF regulated the expression levels of the tight junction (TJ), adhesion junction (AJ), matrix metalloproteinase (MMP), and IL-1ß, as well as reduced BBB permeability, brain edema, and intracranial pressure. Moreover, the FGFR1 antagonist PD 173074 and the ERK antagonist PD 98059 decreased the protective effects of bFGF. CONCLUSIONS bFGF effectively protected the BBB from damage caused by combined injury from IAH and TBI, and binding of FGFR1 and activation of the ERK signaling pathway was involved in these effects.

Cerebrospinal fluid dynamics modulation by diet and cytokines in rats.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a neurological disorder characterised by raised cerebrospinal fluid (CSF) pressure in the absence of any intracranial pathology. IIH mainly affects women with obesity between the ages of 15 and 45. Two possible mechanisms that could explain the increased CSF pressure in IIH are excessive CSF production by the choroid plexus (CP) epithelium or impaired CSF drainage from the brain. However, the molecular mechanisms controlling these mechanisms in IIH remain to be determined. METHODS: In vivo ventriculo-cisternal perfusion (VCP) and variable rate infusion (VRI) techniques were used to assess changes in rates of CSF secretion and resistance to CSF drainage in female and male Wistar rats fed either a control (C) or high-fat (HF) diet (under anaesthesia with 20 µl/100 g medetomidine, 50 µl/100 g ketamine i.p). In addition, CSF secretion and drainage were assessed in female rats following treatment with inflammatory mediators known to be elevated in the CSF of IIH patients: C-C motif chemokine ligand 2 (CCL2), interleukin (IL)-17 (IL-17), IL-6, IL-1ß, tumour necrosis factor-α (TNF-α), as well as glucocorticoid hydrocortisone (HC). RESULTS: Female rats fed the HF diet had greater CSF secretion compared to those on control diet (3.18 ± 0.12 µl/min HF, 1.49 ± 0.15 µl/min control). Increased CSF secretion was seen in both groups following HC treatment (by 132% in controls and 114% in HF) but only in control rats following TNF-α treatment (137% increase). The resistance to CSF drainage was not different between control and HF fed female rats (6.13 ± 0.44 mmH2O min/µl controls, and 7.09 ± 0.26 mmH2O min/µl HF). and when treated with CCL2, both groups displayed an increase in resistance to CSF drainage of 141% (controls) and 139% (HF) indicating lower levels of CSF drainage. CONCLUSIONS: Weight loss and therapies targeting HC, TNF-α and CCL2, whether separately or in combination, may be beneficial to modulate rates of CSF secretion and/or resistance to CSF drainage pathways, both factors likely contributing to the raised intracranial pressure (ICP) observed in female IIH patients with obesity.

Hypertensive Response to Ischemic Stroke in the Normotensive Wistar Rat.

Background and Purpose- Over 80% of ischemic stroke patients show an abrupt increase in arterial blood pressure in the hours and days following ischemic stroke. Whether this poststroke hypertension is beneficial or harmful remains controversial and the underlying physiological basis is unclear. Methods- To investigate the dynamic cardiovascular response to stroke, adult Wistar rats (n=5-8 per group, 393±34 g) were instrumented with telemeters to blood pressure, intracranial pressure, renal sympathetic nerve activity, and brain tissue oxygen in the predicted penumbra (Po2). After 2 weeks of recovery, cardiovascular signals were recorded for a 3-day baseline period, then ischemic stroke was induced via transient middle cerebral artery occlusion, or sham surgery. Cardiovascular signals were then recorded for a further 10 days, and the functional sensorimotor recovery assessed using the cylinder and sticky dot tests. Results- Baseline values of all variables were similar between groups. Compared to sham, in the 2 days following stroke middle cerebral artery occlusion produced an immediate, transient rise above baseline in mean blood pressure (21±3 versus 2±4 mm Hg; P<0.001), renal sympathetic nerve activity (54±11% versus 7±4%; P=0.006), and cerebral perfusion pressure (12±5 versus 1±4; P≤0.001). Intracranial pressure increased more slowly, peaking 3 days after middle cerebral artery occlusion (14±6 versus -1±1 mm Hg; P<0.001). Treating with the antihypertensive agent nifedipine after stroke (1.5-0.75 mg/kg per hour SC) ameliorated poststroke hypertension (12±3 mm Hg on day 1; P=0.041), abolished the intracranial pressure increase (3±1; P<0.001) and reduced cerebral perfusion pressure (10±3 mm Hg; P=0.017). Preventing poststroke hypertension affected neither the recovery of sensorimotor function nor infarct size. Conclusions- These findings suggest that poststroke hypertension is immediate, temporally matched to an increase in sympathetic outflow, and elevates cerebral perfusion pressure for several days after stroke, which may enhance cerebral perfusion. Preventing poststroke hypertension does not appear to worsen prognosis after stroke in young, normotensive, and otherwise healthy rats. Visual Overview- An online visual overview is available for this article.

Dexmedetomidine attenuates the increase of ultrasonographic optic nerve sheath diameter as a surrogate for intracranial pressure in patients undergoing robot-assisted laparoscopic prostatectomy: A randomized double-blind controlled trial.

BACKGROUND: Pneumoperitoneum and steep Trendelenburg position during robot-assisted laparoscopic prostatectomy (RALP) can increase intracranial pressure (ICP). Dexmedetomidine, a highly selective alpha-2 adrenergic receptor agonist, can cause cerebral vasoconstriction and decrease cerebral blood flow by stimulating the postsynaptic alpha-2 adrenergic receptors on cerebral blood vessels. However, the effects of dexmedetomidine on ICP are controversial and have not been evaluated during RALP under the establishment of pneumoperitoneum in the steep Trendelenburg position. Therefore, we evaluated the effect of dexmedetomidine on optic nerve sheath diameter (ONSD) as a surrogate for assessing ICP during RALP. METHODS: Patients were randomly allocated to receive dexmedetomidine (n = 63) (loading dose, 1 µg/kg for 10 minutes and continuous infusion, 0.4 µg/kg/hr) or normal saline (n = 63). The ONSD was measured at 10 minutes after induction of anesthesia in the supine position (T1), 30 minutes (T2) and 60 minutes (T3) after establishment of pneumoperitoneum in the steep Trendelenburg position, and at closing the skin in the supine position (T4). Hemodynamic and respiratory variables were measured at every time point. RESULTS: ONSDs at T2, T3, and T4 were significantly smaller in the dexmedetomidine group than in the control group (5.26 ±â€Š0.25 mm vs 5.71 ±â€Š0.26 mm, 5.29 ±â€Š0.24 mm vs 5.81 ±â€Š0.23 mm, and 4.97 ±â€Š0.24 mm vs 5.15 ±â€Š0.28 mm, all P <.001). ONSDs at T2, T3, and T4 were significantly increased compared to T1 in both groups. Hemodynamic and respiratory variables, except heart rate, did not significantly differ between the 2 groups. The bradycardia and atropine administration were not significantly different between the 2 groups. CONCLUSION: Dexmedetomidine attenuates the increase of ONSD during RALP, suggesting that intraoperative dexmedetomidine administration may effectively attenuate the ICP increase during pneumoperitoneum in the Trendelenburg position.

Idiopathic intracranial hypertension: Are there predictors for visual outcome or recurrences?

OBJECTIVE: To find out the predictors of final visual outcome and recurrences in idiopathic intracranial hypertension (IIH). PATIENTS AND METHODS: Medical records of 75 patients with IIH were analyzed retrospectively. Gender, age of disease onset (AODO), body mass index (BMI), lumbar puncture opening pressure (LP-OP), visual acuity (VA) in logMAR, optical disc appearance (ODA), visual field (VF) mean deviation (MD), treatment results and recurrence rates were considered. RESULTS: Mean age at onset age was 32.4 years, BMI was 311 kg/m² and median LP-OP was 380 mm H2O. All patients were treated with acetazolamide with a median dose of 1500 mg. The mean follow-up period was 44.8 months. AODO, BMI, LP-OP were not correlated with any of the examination parameters (VA, ODA, VF) at the first or last visit. The correlation between the VA and VF both at the first and last visit was not very powerful. VA of the last visit was fairly correlated with the VA of the first visit. However, the correlation between the last and first visit VF was very good. A very significant improvement in both VA and VF was recorded after treatment. Recurrences were noted in 23%. Demographic and clinical features of the recurring and non-recurring patients were not significantly different in terms of AODO, BMI, LP-OP, VA, VF or ODA. CONCLUSIONS: The patients with IIH respond to treatment with acetazolamide. First visit VF is the main determinant of the final visual outcome. Recurrences cannot be predicted by the demographic or clinical features at presentation.

Early prediction of neurological outcome after barbiturate coma therapy in patients undergoing brain tumor surgery.

After a difficult brain tumor surgery, refractory intracranial hypertension (RICH) may occur due to residual tumor or post-operative complications such as hemorrhage, infarction, and aggravated brain edema. We investigated which predictors are associated with prognosis when using barbiturate coma therapy (BCT) as a second-tier therapy to control RICH after brain tumor surgery. The study included adult patients who underwent BCT after brain tumor surgery between January 2010 and December 2016. The primary outcome was neurological status upon hospital discharge, which was assessed using the Glasgow Outcome Scale (GOS). In the study period, 4,296 patients underwent brain tumor surgery in total. Of these patients, BCT was performed in 73 patients (1.7%). Among these 73 patients, 56 (76.7%) survived to discharge and 25 (34.2%) showed favorable neurological outcomes (GOS scores of 4 and 5). Invasive monitoring of intracranial pressure (ICP) was performed in 60 (82.2%) patients, and revealed that the maximal ICP within 6 h after BCT was significantly lower in patients with favorable neurological outcome as well as in survivors (p = 0.008 and p = 0.028, respectively). Uncontrolled RICH (ICP ≥ 22 mm Hg within 6 h of BCT) was an important predictor of mortality after BCT (adjusted hazard ratio 12.91, 95% confidence interval [CI] 2.788-59.749), and in particular, ICP ≥ 15 mm Hg within 6 h of BCT was associated with poor neurological outcome (adjusted odds ratio 9.36, 95% CI 1.664-52.614). Therefore, early-controlled ICP after BCT was associated with clinical prognosis. There were no significant differences in the complications associated with BCT between the two neurological outcome groups. No BCT-induced death was observed. The active and timely control of RICH may be beneficial for clinical outcomes in patients with RICH after brain tumor surgery.

A randomised trial to compare the increase in intracranial pressure as correlated with the optic nerve sheath diameter during propofol versus sevoflurane-maintained anesthesia in robot-assisted laparoscopic pelvic surgery.

Robot-assisted surgery can cause raised intracranial pressures (ICP) due to steep trendelenburg position and pneumoperitoneum. The choice of anesthetic agents can influence the ICP, which can be measured indirectly by correlating it with the sonographically measured optic nerve sheath diameter (ONSD). In this study, our primary aim was to compare the change from baseline of the ONSD during propofol versus sevoflurane-maintained anesthesia in patients undergoing robotic pelvic surgery. In this prospective, interventional, double-blinded study, we randomised 50 patients into two groups P and S. Subjects in group P received intravenous propofol infusion while those in group S received inhalation sevoflurane for maintenance of anesthesia. The ONSD at fixed intervals was noted as the mean of four values measured using ultrasound in both eyes by two independent anesthesiologists who were blinded to the group allocation. The patient demographics and baseline parameters were similar. The mean maximum rise in ONSD from baseline was 0.01 ± 0.01 cm in group P while it was 0.03 ± 0.01 cm in group S (p = 0.001). Percentage change from baseline in group P was 3.41 ± 1.81% and 8.00 ± 2.95% in group S (p = 0.001). We found a positive correlation between the duration of surgery and the maximum rise in ONSD in group S (p = 0.003), but not in group P. Propofol-based total intravenous anesthesia is more effective than inhalation sevoflurane in attenuating the increase in ICP as correlated with the ONSD during robotic pelvic surgery.Clinical trial registration: Yes; Principal investigator: Nambiath Sujata; Trial number: REF/2016/11/012713 (registered); Trial registry: CTRI- http://ctri.nic.in .

Hypertonic saline maintains coagulofibrinolytic homeostasis following moderate­to­severe traumatic brain injury by regulating monocyte phenotype via expression of lncRNAs.

Traumatic brain injury (TBI) is the most common cause of death and permanent disability in people aged <45, and is associated with secondary brain injury and bleed progression, resulting in increased morbidity and mortality. TBI may also induce innate host defense responses characterized by activation of resident microglia and astrocytes, brain microvascular endothelial cells and peripheral blood monocytes. In the present study, 34 patients with moderate­to­severe traumatic brain injury were randomly divided into two groups, including a 7.5% hypertonic saline (HS) treatment group (4 ml/kg) and 3% HS treatment group (4 ml/kg). The results demonstrated that treatment with 7.5% HS decreased the intracranial pressure and improved coagulofibrinolytic homeostasis. Analysis of the monocyte subsets revealed significant reduction in the proportion of cluster of differentiation (CD)14++CD16+ circulating inflammatory monocytes in the 7.5% HS group. In addition, 7.5% HS treatment downregulated the expression of long non­coding (lnc) RNA2448­11 and lncRNA1403 in the peripheral blood mononuclear cells of patients with TBI. Using reverse transcription­quantitative polymerase chain reaction, it was determined that 7.5% HS regulated the expression of tumor necrosis factor­α, interleukin­1ß, transforming growth factor­ß and thrombomodulin, which are the target genes of lncRNA2448­11 and lncRNA1403. These results indicated that 7.5% HS improved the intracranial pressure and coagulofibrinolytic homeostasis by modulating the phenotype of monocytes through lncRNA2448­11 and lncRNA1403. These findings provided evidence that initial resuscitation with HS imparts functional changes to inflammatory cells following TBI, thereby reducing potential neuroinflammatory events associated with secondary brain injury.

Comparison of the effects of desflurane and total intravenous anesthesia on the optic nerve sheath diameter in robot assisted laparoscopic radical prostatectomy: A randomized controlled trial.

BACKGROUND: Optic nerve sheath diameter (ONSD) is a well-known surrogate marker for intracranial pressure during robot-assisted laparoscopic radical prostatectomies (RALP). ONSD during RALP is known to increase due to elevated intracranial pressure as a result of the steep Trendelenburg position and carbon dioxide pneumoperitoneum. We aimed to compare the effects of total intravenous anesthesia (TIVA) and desflurane anesthesia (DES) on ONSD during RALP. METHODS: Patients scheduled for RALP were enrolled and randomly assigned to the TIVA (propofol and remifentanil) or DES (desflurane and remifentanil) group in this randomized trial. Ultrasonographic measurements of ONSD were conducted before administration of anesthesia (T0), 10 minutes after the Trendelenburg position (T1), 1 hour after the Trendelenburg position (T2), 2 hours after the Trendelenburg position (T3), 10 minutes after resuming the supine position (T4), and at the time of arrival in the post-anaesthetic care unit (T5). The primary outcome measure was the mean ONSD at T2 of the TIVA and DES group during RALP. RESULTS: A total of 56 patients were analysed in this study. The mean ONSD at T1, T2, T3, and T4 were significantly lower for patients in the TIVA group compared with those in the DES group (P = .023, .000, .000, and .003, respectively). CONCLUSION: The mean ONSD for patients in the TIVA group was significantly lower than that in the DES group during the RALP procedure. Our findings suggest that TIVA may be a more suitable anesthetic option for patients at risk of cerebral hypoperfusion.

Effect of infusion speed of 7.5% hypertonic saline on brain edema in patients with craniocerebral injury: An experimental study.

This study firstly used a rat traumatic brain injury model to compare the therapeutic effects of different intravenous infusion speed of 7.5% hypertonic saline (HS). Then the authors applied different delivery rate of 7.5% HS to two groups of patients to figure out the optimal infusion rates. A total of 100 rats were randomly divided into control group, group A (7.5% HS 6 mL/h), group B (7.5% HS 3 mL/h), and group C (7.5% HS 2 mL/h). All rats were established for the brain injury model. A total of 30 patients were selected and randomly divided into group A (250 mL/h) and group B (125 mL/h), with 15 cases in each group. Urine amount was recorded per hour; furthermore, blood was extracted from the patients to measure the levels of AQP4, NKCC1, tumour necrosis factor-α (TNF-a), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). Compared with other groups, the expression levels of NKCC1 and AQP4 mRNA in group A was the lowest (P < 0.05). NKCC1 and AQP4 protein expression levels were the lowest in all the groups (P < 0.05). On the aspect of patients, group A displayed more significant difference compared with B group in terms of AQP4, NKCC1, TNF-a, IL-1ß, and IL-6 (P < 0.05). In the two groups, a significant difference was noted in the urine amount at 4 h after administration (P < 0.05). In our study, infusion of hypertonic saline (250 mL/h) at the optimal rate of 7.5% HS decreased the intracranial pressure, brain tissue edema, and inflammatory cytokine expression; moreover, it can promote brain tissue protection.

Early Administration of Hypertonic-Hyperoncotic Hydroxyethyl Starch (HyperHES) Improves Cerebral Blood Flow and Outcome After Experimental Subarachnoid Hemorrhage in Rats.

OBJECTIVE: Early cytotoxic brain edema may be a decisive factor that maintains cerebral malperfusion after subarachnoid hemorrhage (SAH). In addition, endothelial cell swelling may be an independent factor restricting cerebral blood flow (CBF) in a very early stage after SAH. Immediate and aggressive treatment may be able to restore CBF in this critical period. METHODS: Male Sprague-Dawley rats were subjected to SAH by the endovascular filament model and treated by a bolus of hyperoncotic-hypertonic hydroxyethyl starch (4 mL/kg body weight) immediately after vessel perforation and 150 minutes later (n = 12) or by the same amount of normal saline (n = 9). Mean arterial blood pressure, intracranial pressure, and local CBF over both hemispheres were continuously measured by laser-Doppler flowmetry. Neurologic assessment was performed 24 hours later. Hippocampal damage was assessed by hematoxylin-eosin and Caspase-3 staining. RESULTS: Arterial blood gases and mean arterial blood pressure were not significantly different between the 2 groups. Intracranial pressure was significantly reduced in the treatment group (P < 0.05). Local CBF was significantly improved in the treatment group over both hemispheres (P < 0.05; 180 minutes after treatment, P < 0.01). There was a trend to better neurologic performance in the treatment group. The rate of injured neurons was significantly reduced in animals of the treatment group compared with controls (P < 0.01). The number of Caspase-3-positive neurons in the hippocampal CA1 field was not reduced. CONCLUSIONS: In this study, the effects of very early and repeated treatment with a high-dose hyperoncotic-hypertonic hydroxyethyl starch were investigated. The results of this series show that this therapy can be highly effective to improve CBF and attenuate hippocampal cell damage in the early stage of SAH. Whether delayed cell death could be treated by longer therapy cannot be answered by this study. Because no differential diagnosis of the clinical suspicion of SAH prohibits the administration of hypertonic-hyperoncotic solutions, it may be useful as a first-tier preclinical therapy in suspected SAH and could even be used by emergency rescue services before the patient is admitted to a hospital.