ABSTRACT
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.
Subject(s)
Cognition , Exenatide , Glucagon-Like Peptide-1 Receptor , Intracranial Pressure , Pseudotumor Cerebri , Humans , Exenatide/therapeutic use , Exenatide/pharmacology , Female , Adult , Glucagon-Like Peptide-1 Receptor/agonists , Pseudotumor Cerebri/drug therapy , Pseudotumor Cerebri/physiopathology , Cognition/drug effects , Intracranial Pressure/drug effects , Double-Blind Method , Middle Aged , Peptides/therapeutic use , Peptides/pharmacology , Venoms/therapeutic use , Young Adult , Hypoglycemic Agents/therapeutic useSubject(s)
Antidepressive Agents, Tricyclic , Intracranial Hypertension , Mirtazapine , Humans , Mirtazapine/adverse effects , Intracranial Hypertension/chemically induced , Intracranial Hypertension/diagnosis , Female , Antidepressive Agents, Tricyclic/adverse effects , Intracranial Pressure/drug effects , AdultABSTRACT
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.
Subject(s)
Air Ambulances , Blood Transfusion/methods , Brain Injuries, Traumatic , Crystalloid Solutions , Resuscitation/methods , Ringer's Lactate , Shock, Hemorrhagic , Animals , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/physiopathology , Brain Injuries, Traumatic/therapy , Cerebrovascular Circulation/drug effects , Cerebrovascular Circulation/physiology , Crystalloid Solutions/administration & dosage , Crystalloid Solutions/adverse effects , Disease Models, Animal , Intracranial Pressure/drug effects , Intracranial Pressure/physiology , Multiple Trauma/physiopathology , Multiple Trauma/therapy , Neurophysiological Monitoring/methods , Oxygen Consumption/drug effects , Oxygen Consumption/physiology , Ringer's Lactate/administration & dosage , Ringer's Lactate/adverse effects , Shock, Hemorrhagic/complications , Shock, Hemorrhagic/physiopathology , Shock, Hemorrhagic/therapy , Swine , Treatment OutcomeABSTRACT
Following traumatic brain injury (TBI), raised cerebral lactate/pyruvate ratio (LPR) reflects impaired energy metabolism. Raised LPR correlates with poor outcome and mortality following TBI. We prospectively recruited patients with TBI requiring neurocritical care and multimodal monitoring, and utilised a tiered management protocol targeting LPR. We identified patients with persistent raised LPR despite adequate cerebral glucose and oxygen provision, which we clinically classified as cerebral 'mitochondrial dysfunction' (MD). In patients with TBI and MD, we administered disodium 2,3-13C2 succinate (12 mmol/L) by retrodialysis into the monitored region of the brain. We recovered 13C-labelled metabolites by microdialysis and utilised nuclear magnetic resonance spectroscopy (NMR) for identification and quantification.Of 33 patients with complete monitoring, 73% had MD at some point during monitoring. In 5 patients with multimodality-defined MD, succinate administration resulted in reduced LPR(-12%) and raised brain glucose(+17%). NMR of microdialysates demonstrated that the exogenous 13C-labelled succinate was metabolised intracellularly via the tricarboxylic acid cycle. By targeting LPR using a tiered clinical algorithm incorporating intracranial pressure, brain tissue oxygenation and microdialysis parameters, we identified MD in TBI patients requiring neurointensive care. In these, focal succinate administration improved energy metabolism, evidenced by reduction in LPR. Succinate merits further investigation for TBI therapy.
Subject(s)
Brain Injuries, Traumatic , Brain/metabolism , Energy Metabolism/drug effects , Mitochondria/metabolism , Succinic Acid/administration & dosage , Adult , Brain Injuries, Traumatic/drug therapy , Brain Injuries, Traumatic/metabolism , Female , Humans , Intracranial Pressure/drug effects , Lactic Acid/metabolism , Male , Microdialysis , Middle Aged , Nuclear Magnetic Resonance, Biomolecular , Pyruvic Acid/metabolismABSTRACT
BACKGROUND: The aim of this study was to investigate whether AMN082 exerts its neuroprotective effect by attenuating glutamate receptor-associated neuronal apoptosis and improving functional outcomes after traumatic brain injury (TBI). METHODS: Anesthetized male Sprague-Dawley rats were divided into the sham-operated, TBI + vehicle, and TBI + AMN082 groups. AMN082 (10 mg/kg) was intraperitoneally injected 0, 24, or 48 h after TBI. In the 120 min after TBI, heart rate, mean arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were continuously measured. Motor function, the infarct volume, neuronal nitrosative stress-associated apoptosis, and N-methyl-D-aspartate receptor 2A (NR2A) and NR2B expression in the pericontusional cortex were measured on the 3rd day after TBI. RESULTS: The results showed that the AMN082-treated group had a lower ICP and higher CPP after TBI. TBI-induced motor deficits, the increase in infarct volume, neuronal apoptosis, and 3-nitrotyrosine and inducible nitric oxide synthase expression in the pericontusional cortex were significantly improved by AMN082 therapy. Simultaneously, AMN082 increased NR2A and NR2B expression in neuronal cells. CONCLUSIONS: We concluded that intraperitoneal injection of AMN082 for 3 days may ameliorate TBI by attenuating glutamate receptor-associated nitrosative stress and neuronal apoptosis in the pericontusional cortex. We suggest that AMN082 administration in the acute stage may be a promising strategy for TBI.
Subject(s)
Apoptosis/drug effects , Benzhydryl Compounds/administration & dosage , Brain Injuries, Traumatic/prevention & control , Neurons/drug effects , Neuroprotective Agents/administration & dosage , Animals , Apoptosis/physiology , Brain Injuries, Traumatic/metabolism , Brain Injuries, Traumatic/pathology , Injections, Intraperitoneal , Intracranial Pressure/drug effects , Intracranial Pressure/physiology , Male , Neurons/metabolism , Neurons/pathology , Rats , Rats, Sprague-Dawley , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Receptors, N-Methyl-D-Aspartate/metabolismABSTRACT
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.
Subject(s)
Cerebrovascular Circulation/physiology , Decompressive Craniectomy , Intracranial Hypertension/diagnostic imaging , Intracranial Hypertension/etiology , Intracranial Pressure/physiology , Anti-Infective Agents/pharmacology , Anti-Infective Agents/therapeutic use , Brain Neoplasms/complications , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/therapy , Central Nervous System Infections/complications , Central Nervous System Infections/diagnostic imaging , Central Nervous System Infections/therapy , Cerebral Hemorrhage/complications , Cerebral Hemorrhage/diagnostic imaging , Cerebral Hemorrhage/therapy , Cerebrovascular Circulation/drug effects , Child , Decompressive Craniectomy/methods , Humans , Hydrocephalus/complications , Hydrocephalus/diagnostic imaging , Hydrocephalus/therapy , Intracranial Hypertension/therapy , Intracranial Pressure/drug effects , Stroke/complications , Stroke/diagnostic imaging , Stroke/therapy , Treatment OutcomeABSTRACT
[Figure: see text].
Subject(s)
Blood-Brain Barrier/physiopathology , Hypertension, Renovascular , Intracranial Hypertension , Intracranial Pressure/drug effects , Losartan/pharmacology , Receptor, Angiotensin, Type 1/metabolism , Angiotensin II Type 1 Receptor Blockers/pharmacology , Animals , Disease Models, Animal , Hypertension, Renovascular/complications , Hypertension, Renovascular/drug therapy , Hypertension, Renovascular/metabolism , Hypertension, Renovascular/physiopathology , Intracranial Hypertension/drug therapy , Intracranial Hypertension/etiology , Intracranial Hypertension/metabolism , Paraventricular Hypothalamic Nucleus , Rats , Solitary Nucleus/physiology , Ventral Thalamic Nuclei/physiologyABSTRACT
OBJECTIVES: Mannitol and hypertonic saline are used to treat raised intracerebral pressure in patients with traumatic brain injury, but their possible effects on kidney function and mortality are unknown. DESIGN: A post hoc analysis of the erythropoietin trial in traumatic brain injury (ClinicalTrials.gov NCT00987454) including daily data on mannitol and hypertonic saline use. SETTING: Twenty-nine university-affiliated teaching hospitals in seven countries. PATIENTS: A total of 568 patients treated in the ICU for 48 hours without acute kidney injury of whom 43 (7%) received mannitol and 170 (29%) hypertonic saline. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We categorized acute kidney injury stage according to the Kidney Disease Improving Global Outcome classification and defined acute kidney injury as any Kidney Disease Improving Global Outcome stage-based changes from the admission creatinine. We tested associations between early (first 2 d) mannitol and hypertonic saline and time to acute kidney injury up to ICU discharge and death up to 180 days with Cox regression analysis. Subsequently, acute kidney injury developed more often in patients receiving mannitol (35% vs 10%; p < 0.001) and hypertonic saline (23% vs 10%; p < 0.001). On competing risk analysis including factors associated with acute kidney injury, mannitol (hazard ratio, 2.3; 95% CI, 1.2-4.3; p = 0.01), but not hypertonic saline (hazard ratio, 1.6; 95% CI, 0.9-2.8; p = 0.08), was independently associated with time to acute kidney injury. In a Cox model for predicting time to death, both the use of mannitol (hazard ratio, 2.1; 95% CI, 1.1-4.1; p = 0.03) and hypertonic saline (hazard ratio, 1.8; 95% CI, 1.02-3.2; p = 0.04) were associated with time to death. CONCLUSIONS: In this post hoc analysis of a randomized controlled trial, the early use of mannitol, but not hypertonic saline, was independently associated with an increase in acute kidney injury. Our findings suggest the need to further evaluate the use and choice of osmotherapy in traumatic brain injury.
Subject(s)
Acute Kidney Injury/metabolism , Brain Injuries, Traumatic/therapy , Diuretics, Osmotic/therapeutic use , Erythropoietin/metabolism , Mannitol/therapeutic use , Saline Solution, Hypertonic/therapeutic use , Acute Kidney Injury/etiology , Brain Injuries, Traumatic/drug therapy , Diuretics, Osmotic/adverse effects , Female , Fluid Therapy/methods , Humans , Intracranial Pressure/drug effects , Male , Mannitol/adverse effects , Treatment OutcomeABSTRACT
INTRODUCTION: Intracerebral haemorrhage (ICH) is associated with high morbidity and mortality. Blood pressure (BP) control is one of the main management strategies in acute ICH. Limited data currently exist regarding intracranial pressure (ICP) in acute ICH. The relationship between BP lowering and ICP is yet to be fully elucidated. METHODS: We conducted a systematic review to investigate the effects of BP lowering on ICP in acute ICH. The study protocol was registered on PROSPERO (CRD42019134470). RESULTS: Following PRISMA guidelines, MEDLINE, EMBASE and CENTRAL were searched for studies on ICH with BP and ICP or surrogate measures. 1096 articles were identified after duplicates were removed; 18 studies meeting the inclusion criteria. Dihydropyridine calcium channel blockers (CCBs) were the most common agent used to lower BP, but had a varying effect on ICP. Other BP-lowering agents used also had a varying effect on ICP. DISCUSSION AND CONCLUSION: Further work, including large observational or randomized interventional studies, is needed to develop a better understanding of the effect of BP lowering on ICP in acute ICH, which will assist the development of more effective management strategies. TRIAL REGISTRATION: The study protocol was registered on PROSPERO (CRD42019134470) on 29/05/2019.
Subject(s)
Antihypertensive Agents/therapeutic use , Blood Pressure/drug effects , Cerebral Hemorrhage/drug therapy , Intracranial Pressure/drug effects , Adolescent , Adult , Aged , Aged, 80 and over , Cerebral Hemorrhage/diagnosis , Cerebral Hemorrhage/physiopathology , Female , Humans , Male , Middle Aged , Treatment Outcome , Young AdultABSTRACT
Intracranial pressure (ICP) has to be maintained quite constant, because increased ICP caused by cerebrovascular disease and head trauma is fatal. Although controlling ICP is clinically critical, only few therapeutic methods are currently available. Barbiturates, a group of sedative-hypnotic drugs, are recognized as secondary treatment for controlling ICP. We proposed a novel "step-down infusion" method, administrating barbiturate (thiamylal) after different time point from the start of treatment under normothermia, at doses of 3.0 (0-24 h), 2.0 (24-48 h), 1.5 (48-72 h), and 1.0 mg/kg/h (72-96 h), and evaluated its safety and effectiveness in clinical. In 22 patients with severe traumatic brain injury or severe cerebrovascular disease (Glasgow coma scale ≤8), thiamylal concentrations and ICP were monitored. The step-down infusion method under normothermia maintained stable thiamylal concentrations (<26.1 µg/ml) without any abnormal accumulation/elevation, and could successfully keep ICP <20 mmHg (targeted management value: ICP <20 mmHg) in all patients. Moreover the mean value of cerebral perfusion pressure (CPP) was also maintained over 65 mmHg during all time course (targeted management value: CPP >65 mmHg), and no threatening changes in serum potassium or any hemodynamic instability were observed. Our novel "step-down infusion" method under normothermia enabled to maintain stable, safe thiamylal concentrations to ensure both ICP reduction and CPP maintenance without any serious side effects, may provide a novel and clinically effective treatment option for patients with increased ICP.
Subject(s)
Brain Injuries, Traumatic/drug therapy , Cerebrovascular Disorders/drug therapy , Hypnotics and Sedatives/administration & dosage , Intracranial Hypertension/drug therapy , Thiamylal/administration & dosage , Adult , Aged , Aged, 80 and over , Brain Injuries, Traumatic/blood , Brain Injuries, Traumatic/complications , Cerebrovascular Disorders/complications , Cerebrovascular Disorders/diagnosis , Dose-Response Relationship, Drug , Female , Glasgow Coma Scale , Humans , Hypnotics and Sedatives/adverse effects , Hypnotics and Sedatives/pharmacokinetics , Infusions, Intravenous/methods , Injury Severity Score , Intracranial Hypertension/diagnosis , Intracranial Hypertension/etiology , Intracranial Pressure/drug effects , Male , Middle Aged , Thiamylal/adverse effects , Thiamylal/pharmacokinetics , Treatment OutcomeABSTRACT
Maintaining an adequate level of sedation and analgesia plays a key role in the management of traumatic brain injury (TBI). To date, it is unclear which drug or combination of drugs is most effective in achieving these goals. Ketamine is an agent with attractive pharmacological and pharmacokinetics characteristics. Current evidence shows that ketamine does not increase and may instead decrease intracranial pressure, and its safety profile makes it a reliable tool in the prehospital environment. In this point of view, we discuss different aspects of the use of ketamine in the acute phase of TBI, with its potential benefits and pitfalls.
Subject(s)
Brain Injuries, Traumatic/drug therapy , Ketamine/pharmacology , Time Factors , Anesthetics, Dissociative/pharmacology , Anesthetics, Dissociative/therapeutic use , Brain Injuries, Traumatic/physiopathology , Humans , Hypnotics and Sedatives/pharmacology , Hypnotics and Sedatives/therapeutic use , Intracranial Pressure/drug effects , Ketamine/therapeutic useABSTRACT
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.
Subject(s)
Cognition/physiology , Cranial Sutures/physiopathology , Craniosynostoses/physiopathology , Regeneration/physiology , Skull/physiopathology , Animals , Behavior, Animal/drug effects , Cognition/drug effects , Craniosynostoses/genetics , Dura Mater/pathology , Dura Mater/physiopathology , Gelatin/pharmacology , Gene Expression Profiling , Hand Strength , Intracranial Pressure/drug effects , Intracranial Pressure/physiology , Locomotion/drug effects , Mesenchymal Stem Cells/drug effects , Methacrylates/pharmacology , Mice, Inbred C57BL , Motor Activity/drug effects , Organ Size/drug effects , Regeneration/drug effects , Skull/pathology , Twist-Related Protein 1/metabolism , Wnt Signaling Pathway/drug effectsABSTRACT
BACKGROUND: Addison disease, corticosteroid withdrawal, and taking synthetic growth hormone have been linked with development of intracranial hypertension, but there is still debate on whether administration of other exogenous hormones plays a role in precipitating elevated pressure. The growing use of hormonal therapy for gender affirmation provides an opportunity to explore this possibility. METHODS: All transgender patients taking exogenous hormones for female-to-male (FTM) and male-to-female (MTF) transitions who were diagnosed with intracranial hypertension at Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital and Beth Israel Deaconess Medical Center between August 2014 and November 2018 were included in a retrospective review. Visual acuity, type, and dose of exogenous hormone, visual field testing, clinical exam, results of neuroimaging and lumbar puncture, and treatment modalities were catalogued and analyzed. RESULTS: Six transgender individuals were identified. Five were FTM, with an average hormone treatment time of 18.4 months, and one was MTF who had been treated with hormones for 4 years. The average age of all patients was 23.5 years. The average time between onset of symptoms and presentation was 5 months. Fifty percent of the patients reported pulse-synchronous tinnitus, 83% reported positional headache, 33% reported transient visual obscurations, and 16% reported diplopia. Lumbar punctures performed on 4 of the patients revealed elevated opening pressures and normal cerebrospinal fluid constituents. MRI findings consistent with elevated intracranial pressure (ICP) were present in the other 2 patients in whom lumbar puncture was unsuccessful. Four patients were treated with acetazolamide and one was treated with topiramate, with an average follow-up time of 15.7 months. All patients demonstrated bilateral optic disc swelling, and all maintained normal acuity and color vision. Performance on visual field testing was not significantly affected in any patient. CONCLUSIONS: This is the largest reported series to date of gender-transitioning patients with intracranial hypertension, including one novel MTF conversion. These observations warrant further investigation into the possible link of exogenous hormonal therapy and elevated ICP and any mechanisms or confounders underlying this potential association.
Subject(s)
Gonadal Steroid Hormones/adverse effects , Intracranial Hypertension/chemically induced , Intracranial Pressure/drug effects , Sex Reassignment Procedures/methods , Transgender Persons , Adult , Female , Humans , Intracranial Hypertension/physiopathology , Male , Retrospective Studies , Young AdultSubject(s)
Brain Neoplasms/therapy , Cerebellar Neoplasms/therapy , Growth Hormone/adverse effects , Intracranial Pressure/physiology , Medulloblastoma/pathology , Antineoplastic Agents/therapeutic use , Brain Neoplasms/pathology , Cerebellar Neoplasms/pathology , Child, Preschool , Growth Hormone/therapeutic use , Humans , Intracranial Pressure/drug effects , Male , Medulloblastoma/drug therapy , Medulloblastoma/radiotherapyABSTRACT
OBJECTIVE: We conducted this prospective self-crossover controlled trial to compare the efficacy and safety of 10 % hypertonic saline (HS) and 20 % mannitol in doses of similar osmotic burden for the treatment of increased intracranial pressure (ICP) in patients with large hemispheric infarction (LHI). PATIENTS AND METHODS: Patients with LHI were enrolled from January 2017 to January 2018. We used an alternating treatment protocol to compare the effects of HS with mannitol given for episodes of increased ICP in patients with LHI. Indicators such as ICP, mean arterial pressure (MAP) and cerebral perfusion pressure (CPP) were continuously monitored at regular intervals for 240â¯min after initiation of infusion. Electrolytes, plasma osmolality and renal functions were measured before and 240â¯min after initiation of infusion to compare the efficacy and safety of the two drugs. RESULTS: A total of 49 episodes of increased ICP occurred in 14 patients with LHI, of which 24 were infused with 10 % HS and 25 with 20 % mannitol. Both the treatments were equally effective in reducing ICP (Pâ¯<â¯0.01). The differences in the duration and degree of reduction were not significant between the groups (Pâ¯>â¯0.05). Although both the osmolar agents decreased MAP, the degree was greater in the mannitol group (Pâ¯<â¯0.05) at T120. The increase in CPP was greater in the HS group compared with the mannitol group (Pâ¯<â¯0.05) at T120. However, HS was associated with faster heart rate (HR) and higher serum chloride levels (Pâ¯<â¯0.05). Changes in serum sodium levels and osmolality were not significant between the groups in spite of being higher in the HS group. CONCLUSIONS: Both the drugs can serve as first-line agents for treating intracranial hypertension caused by LHI and should be selected rationally according to the differences in efficacy and adverse effects.
Subject(s)
Cerebrovascular Circulation/drug effects , Diuretics, Osmotic/pharmacology , Intracranial Hypertension/drug therapy , Mannitol/pharmacology , Saline Solution, Hypertonic/pharmacology , Adult , Aged , Diuretics, Osmotic/administration & dosage , Humans , Infarction/complications , Infarction/drug therapy , Intracranial Hypertension/etiology , Intracranial Pressure/drug effects , Male , Mannitol/administration & dosage , Middle Aged , Osmolar Concentration , Prospective StudiesABSTRACT
BACKGROUND: The aim was to study the effects of barbiturate coma treatment (BCT) on intracranial pressure (ICP) and intracranial compensatory reserve (RAP index) in children (< 17 years of age) with traumatic brain injury (TBI) and refractory intracranial hypertension (RICH). METHODS: High-resolution monitoring data were used to study the effects of BCT on ICP, mean arterial pressure (MAP), cerebral perfusion pressure (CPP), and RAP index. Four half hour long periods were studied: before bolus injection and at 5, 10, and 24 hours thereafter, respectively, and a fifth tapering period with S-thiopental between < 100 and < 30 µmol/L. S-thiopental concentrations and administered doses were registered. RESULTS: Seventeen children treated with BCT 2007-2017 with high-resolution data were included; median age 15 (range 6-17) and median Glasgow coma score 7 (range 3-8). Median time from trauma to start of BCT was 44.5 h (range 2.5-197.5) and from start to stop 99.0 h (range 21.0-329.0). Median ICP was 22 (IQR 20-25) in the half hour period before onset of BCT and 16 (IQR 11-20) in the half hour period 5 h later (p = 0.011). The corresponding figures for CPP were 65 (IQR 62-71) and 63 (57-71) (p > 0.05). The RAP index was in the half hour period before onset of BCT 0.6 (IQR 0.1-0.7), in the half hour period 5 h later 0.3 (IQR 0.1-0.7) (p = 0.331), and in the whole BCT period 0.3 (IQR 0.2-0.4) (p = 0.004). Eighty-two percent (14/17) had favorable outcome (good recovery = 8 patients and moderate disability = 6 patients). CONCLUSION: BCT significantly reduced ICP and RAP index with preserved CPP. BCT should be considered in case of RICH.
Subject(s)
Barbiturates/pharmacology , Brain Injuries, Traumatic/therapy , Coma/chemically induced , Convulsive Therapy/methods , Intracranial Hypertension/therapy , Intracranial Pressure/drug effects , Adolescent , Anticonvulsants/therapeutic use , Arterial Pressure/drug effects , Barbiturates/administration & dosage , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/drug therapy , Cerebrovascular Circulation/drug effects , Child , Female , Humans , Intracranial Hypertension/drug therapy , Intracranial Hypertension/etiology , Male , Retrospective Studies , Thiopental/therapeutic useABSTRACT
Management of acute neurologic disorders in the emergency department is multimodal and may require the use of medications to decrease morbidity and mortality secondary to neurologic injury. Clinicians should form an individualized treatment approach with regard to various patient specific factors. This review article focuses on the pharmacotherapy for common neurologic emergencies that present to the emergency department, including traumatic brain injury, central nervous system infections, status epilepticus, hypertensive emergencies, spinal cord injury, and neurogenic shock.
Subject(s)
Emergency Service, Hospital , Nervous System Diseases/drug therapy , Anticonvulsants/therapeutic use , Brain Injuries, Traumatic/drug therapy , Central Nervous System Infections/drug therapy , Emergencies , Humans , Intracranial Pressure/drug effects , Neuropharmacology , Status Epilepticus/drug therapyABSTRACT
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.
Subject(s)
Central Nervous System Neoplasms/complications , Central Nervous System Neoplasms/drug therapy , Intracranial Pressure/drug effects , Lymphoma, Non-Hodgkin/complications , Lymphoma, Non-Hodgkin/drug therapy , Methotrexate/adverse effects , Adult , Female , HumansABSTRACT
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).
Subject(s)
Brain Diseases/physiopathology , Intracranial Pressure/drug effects , Intubation, Intratracheal , Propofol/therapeutic use , Suction , Adult , Female , Glasgow Outcome Scale , Humans , Hypnotics and Sedatives/therapeutic use , Intracranial Pressure/physiology , Male , Middle Aged , Prognosis , Suction/adverse effectsABSTRACT
BACKGROUND: Intravenous hypertonic saline is utilized commonly in critical care for treatment of acute or refractory elevations of intracranial pressure (ICP) in traumatic brain injury (TBI) patients. Though there is a clear understanding of the general physiological effects of a hypertonic saline solution over long periods of time, smaller epoch effects of hypertonic saline (HTS) have not been thoroughly analyzed. The aim of this study was to perform a direct evaluation of the high-frequency response of HTS on the cerebrovascular physiological responses in TBI. METHODS: We retrospectively reviewed our prospectively maintained adult TBI database for those with archived high-frequency cerebral physiology and available HTS treatment information. We evaluated different epochs of physiology around HTS bolus dosing, comparing pre- with post-HTS. We assessed for changes in slow fluctuations in ICP, pulse amplitude of ICP (AMP), cerebral perfusion pressure (CPP), mean arterial pressure (MAP), cerebrovascular reactivity (as measured through pressure reactivity index (PRx)), and cerebral compensatory reserve (correlation (R) between AMP (A) and ICP (P)). Comparisons of mean measures and percentage time above clinically relevant thresholds for the physiological parameters were compared pre- and post-HTS using descriptive statistics and Mann-Whitney U testing. We assessed for subgroups of physiological responses using latent profile analysis (LPA). RESULTS: Fifteen patients underwent 69 distinct bolus infusions of hypertonic saline. Apart from the well-documented decrease in ICP, there was also a reduction in AMP. The analysis of cerebrovascular reactivity response to HTS solution had two main effects. For patients with grossly impaired cerebrovascular reactivity pre-HTS (PRx > + 0.30), HTS bolus led to improved reactivity. However, for those with intact cerebrovascular reactivity pre-HTS (PRx < 0), HTS bolus demonstrated a trend towards more impaired reactivity. This indicates that HTS has different impacts, dependent on pre-bolus cerebrovascular status. There was no significant change in metrics of cerebral compensatory reserve. LPA failed to demonstrate any subgroups of physiological responses to HTS administration. CONCLUSIONS: The direct decrease in ICP and AMP confirms that a bolus dose of a HTS solution is an effective therapeutic agent for intracranial hypertension. However, in patients with intact autoregulation, hypertonic saline may impair cerebral hemodynamics. These findings regarding cerebrovascular reactivity remain preliminary and require further investigation.