Detection of Intracranial Hypertension using Deep Learning.

During long-term missions, some astronauts experience structural and functional changes of the eyes and brain which resemble signs/symptoms experienced by patients with intracranial hypertension. Weightlessness prevents the normal cerebral volume and pressure 'unloading' associated with upright postures on Earth, which may be part of the cerebral and ocular pathophysiology. By placing the lower body in a negative pressure device (LBNP) that pulls fluid away from cranial compartments, we simulated effects of gravity and significantly lowered pressure within the brain parenchyma and ventricle compartments. Application of incremental LBNP demonstrated a non-linear dose-response curve, suggesting 20mmHg LBNP as the optimal level for reducing pressure in the brain without impairing cerebral perfusion pressure. This non-invasive method of reducing pressure in the brain holds potential as a countermeasure in space as well as having treatment potential for patients on Earth with traumatic brain injury or other pathology leading to intracranial hypertension. Patients with elevated intracranial pressure (ICP) exhibit neuro-ocular symptoms including headache, papilloedema and loss of vision. Some of these symptoms are also present in astronauts during and after prolonged space-flight where lack of gravitational stress prevents daily lowering of ICP associated with upright posture. Lower body negative pressure (LBNP) simulates the effects of gravity by displacing fluid caudally and we hypothesized that LBNP would lower ICP without compromising cerebral perfusion. Ten cerebrally intact volunteers were included: six ambulatory neurosurgical patients with parenchymal ICP-sensors and four former cancer patients with Ommaya-reservoirs to the frontal horn of a lateral ventricle. We applied LBNP while recording ICP and blood pressure while supine, and during simulated intracranial hypertension by 15° head-down tilt. LBNP from 0 to 50mmHg at increments of 10mmHg lowered ICP in a non-linear dose-dependent fashion; when supine (n=10), ICP was decreased from 15±2mmHg to 14±4, 12±5, 11±4, 10±3 and 9±4mmHg, respectively (P<0.0001). Cerebral perfusion pressure (CPP), calculated as mean arterial blood pressure at midbrain level minus ICP, was unchanged (from 70±12mmHg to 67±9, 69±10, 70±12, 72±13 and 74±15mmHg; P=0.02). A 15° head-down tilt (n=6) increased ICP to 26±4mmHg, while application of LBNP lowered ICP (to 21±4, 20±4, 18±4, 17±4 and 17±4mmHg; P<0.0001) and increased CPP (P<0.01). An LBNP of 20mmHg may be the optimal level to lower ICP without impairing CPP to counteract spaceflight-associated neuro-ocular syndrome in astronauts. Furthermore, LBNP holds clinical potential as a safe, non-invasive method for lowering ICP and improving CPP for patients with pathologically elevated ICP on Earth.

Spontaneous intracranial hypotension (SIH) is a debilitating disorder, with an estimated annual incidence of 3.7 per 100,000. Diagnosing SIH can be challenging for clinicians, as patients frequently present with normal investigation findings. Intracranial pressure (ICP) monitoring has been proposed as a valuable tool for patients with orthostatic headaches that are highly suggestive of SIH but have inconclusive investigation results. The primary objective of this study was to determine the proportion of patients with spontaneous orthostatic headaches and normal diagnostic work-up who exhibited abnormal ICP monitoring results. This single-centre, retrospective observational study was conducted at a tertiary referral centre specialising in SIH and CSF dynamics disorders. Consecutive patients with spontaneous orthostatic headaches and inconclusive diagnostic work-up who underwent 24-hour ICP monitoring were considered eligible. The 24-hour ICP monitoring followed a standardised protocol, measuring median ICP and pulse amplitude (a marker of brain compliance) during the daytime, nighttime, and over the entire 24-hour period. Specific cut-offs for low and high ICP states were predetermined based on the best available current evidence. Thirty-eight patients (23 females, mean age 41 years ± 14SD) were identified. All patients had orthostatic headaches with a spontaneous onset. The mean duration of symptoms was 46 months ± 36SD. ICP monitoring identified 3 patients (7.9%) with low ICP (mean of the median 24-hour ICP - 2 mmHg ± 2SD) and 6 patients (15.8%) with high ICP (mean of the median 24-hour ICP 9 mmHg ± 3SD). Obvious CSF dynamics disturbances were excluded in the remaining 29 patients (76.3%, mean of the median 24-hour ICP 3 mmHg ± 3SD). The only clinical feature that was more common in patients with abnormal ICP compared to patients with normal ICP results was audiovestibular disturbance, namely aural fullness or muffled hearing (67% versus 17%, p = 0.015). There were no complications from the ICP monitoring procedure for any patient. When appropriately selected, patients with a clinical picture highly suggestive of SIH, who have a negative diagnostic work-up, may benefit from consideration of invasive ICP monitoring. Moreover, a significant minority of patients with orthostatic headache may paradoxically have a high CSF pressure state, which can be detected using ICP monitoring. Portions of this work were presented in abstract and oral presentation form at the Twenty-eighth Anglo-Dutch Migraine Association meeting (08/06/2018), the Tenth Meeting of the International Society for Hydrocephalus and Cerebrospinal Fluid Disorders (20/10/2018; Bologna, Italy), the Society of British Neurological Surgeons 2018 Autumn Meeting (19/09/2018; London, United Kingdom), and the European Association of Neurosurgical Societies 2023 congress (27/09/2023; Barcelona, Spain). This work is also part of the doctoral thesis of one of the authors (LD).

To the Editor: Sir, the study by Canhao and colleagues made the important point that the most frequent cause of death in patients with cerebral venous thrombosis (CVT) is transtentorial herniation and that these patients may potentially have benefited from decompressive hemicraniectomy.1 We would like to corroborate this argument by providing evidence for a rise in intracranial pressure (ICP) preceding brain herniation and death in a patient with CVT. A 29-year-old pregnant woman who presented with confusion and vomiting was admitted to a district general hospital. A right-sided weakness developed within 2 days. A CT brain scan showed a left temporal hemorrhage without mass effect. Her Glasgow Coma Scale score dropped to 8/15; she was intubated and transferred to the neurocritical care …

Background: In some patients with hydrocephalus or idiopathic intracranial hypertension, symptoms continue after shunt operation. In these cases, elevated or lowered intracranial pressure (ICP) can be handled with adjustments of the shunt valves. The use of telemetric ICP measurements may help confirm clinical suspicion of cerebrospinal fluid underdrainage or overdrainage. We standardized measurements with a simple, repeatable maneuver for outpatient telemetric ICP recording and evaluated its test-retest reliability. Methods: Data of patients who underwent ventriculoperitoneal or ventriculoatrial shunt placement and subsequent telemetric ICP sensor implantation were retrospectively reviewed. Telemetric ICP recordings in patients were conducted in the following manner: The standing-supine-sitting paradigm requires postural changes in 10-minute intervals over 30 minutes. First, the patient is requested to walk; second, to lay down; third, to sit down with a headrest elevation of 60°. ICP data (in mmHg) were reported as mean ± SD values. Test-retest validity was assessed using Pearson correlation analysis and Bland Altmann Plots. Results: We evaluated 85 ICP datasets obtained repeatedly with a time difference of at least 24 hours. Overall test-retest reliability was excellent (Pearson correlation coefficient 0.99, P < 0.001), as were the scores for individual postures: standing (correlation 0.98, P < 0.001), supine (correlation 0.98, P < 0.001), and sitting (correlation 0.99, P < 0.001). A Blande Altman Plot showed no significant differences between the measurements. Further, we analyzed a possible influence of telemetric measurements on the decision-making for shunt valve adjustments, finding no significant data, probably mainly due to the retrospective design. Conclusions: We confirmed high test-retest reliability of the standing-supine-sitting paradigm for telemetric ICP measurements in the outpatient setting. Prospective studies are needed to proof a positive influence on the decision-making.

The presence of elevated intracranial pressure (ICP) in patients with cerebral edema secondary to non-taumatic, non-neoplastic encephalopathies has been well documented, usually via lumbar puncture. Few reports exist however of continuous ICP monitoring of patients with nontraumatic cerebral edema (5, 6, 11). We are reporting our experience in monitoring and controlling ICP in 15 such patients.

This review was undertaken to determine whether high intracranial pressure (ICP) during reperfusion after hypothermic circulatory arrest (HCA) correlates with evidence of suboptimal cerebral protection in a chronic porcine model. In concurrent studies of cerebral protection, 48 control pigs (24-31 kg) underwent 90 min of HCA at 20 degrees C using a strictly standardized protocol. Hemodynamic measurements, ICP and neurophysiological data (EEG, SSEP) were assessed before HCA and until 3 h postoperatively. ICP was measured using a Codman microtip catheter inserted directly into brain parenchyma. Neurological/behavioral evaluation (9=full recovery) was carried out daily through postoperative day (POD) 3. There were no significant hemodynamic or metabolic differences between individual animals. ICP (mmHg) increased significantly for the first 3 h after HCA: from baseline levels of 6.2+/-2.1 to 10+/-2.6 at 1 h, 11+/-3.2 at 2 h and 10+/-3.6 mmHg at 3 h; P<0.001 for the trend. EEG recovery 3 h after HCA was observed in 13 animals (27%), and correlated with lower ICP during reperfusion (P<0.001): with each 1 mmHg increase in ICP at 3 h, the odds of early EEG recovery decreased by a factor of 0.72. Lower ICP during reperfusion was also significantly associated with higher behavioral scores on POD 1 and 2, P<0.001. A significant rise in ICP may help explain the prolonged obtundation and confusion often seen clinically after HCA. If these small but consistent increases in ICP contribute to rather than reflect ischemic neuronal damage, simple maneuvers to reduce ICP may improve cerebral recovery after HCA.

Optimal cerebral perfusion pressure (CPPopt) is an autoregulatory-oriented target in the neurointensive care (NIC) of patients with traumatic brain injury (TBI), and deviation from CPPopt is associated with poor outcome. We recently found that blood pressure variability (BPV) is associated with deviation from CPPopt. To evaluate BPV and other variables related to deviation from CPPopt and to evaluate challenges and strategies for autoregulatory-oriented treatment in TBI. Data including arterial blood pressure and intracranial pressure (ICP) from 362 TBI patients treated at the NIC unit, Uppsala University Hospital, Sweden, between 2008 and 2016, were retrospectively analyzed day 2 to 5. Higher BPV was a strong predictor of both CPP deviation below and above CPPopt after multiple regression analyses. There was no other explanatory variable for CPP deviation above CPPopt, whereas also higher ICP and worse autoregulation (higher pressure reactivity index) were associated with CPP deviation below CPPopt. A higher BPV was, in turn, explained by older age, lower ICP, higher mean arterial blood pressure, and higher slow arterial blood pressure amplitude (0.018-0.067 Hz). BPV was strongly associated with deviation from CPPopt. High age is a risk factor for high BPV and hence CPP insults. Our treatment protocol is focused on avoiding CPP below 60 mm Hg. It is possible that a more restrictive upper level could generate more stable blood pressure and less deviation from CPPopt.

Intracranial pressure (ICP) elevation is a compartment syndrome that impairs blood flow to the brain. Despite the importance of ICP values in neurocritical care, normal ICP values and the precise ICP threshold at which treatment should be initiated remain uncertain. To refine our understanding of normal ICP values and determine the ICP threshold most strongly associated with outcome. Prospective observational study (2004-2010), with outcomes determined at hospital discharge. The study included neurocritical care patients from a single level I trauma center, San Francisco General Hospital. Three hundred eighty-three patients had a traumatic brain injury with or without craniectomy; 140 patients had another indication for ICP monitoring. Consecutive patients were studied. Data analyses were completed between March 2015 and December 2019. Five hundred twenty-three ICP-monitored patients. A computer system prospectively and automatically collected 1-minute physiologic data from patients in the intensive care unit during a 6-year period. Mean ICP was calculated, as was the proportion of ICP values greater than thresholds from 1 to 80 mm Hg in 1-mm Hg increments. The association between these measures and outcome was explored for various epochs up to 30 days from the time of injury. A principal component analysis was used to explore physiologic changes at various ICP thresholds, and elastic net regression was used to identify ICP thresholds most strongly associated with Glasgow Outcome Scale score at discharge. Of the 523 studied patients, 70.7% of studied patients were men (n = 370) and 72.1% had a traumatic brain injury (n = 377). A total of 4 090 964 1-minute ICP measurements were recorded for the included patients (7.78 years of recordings). Intracranial pressure values of 8 to 9 mm Hg were most commonly recorded and could possibly reflect normal values. The principal component analysis suggested state shifts in the physiome occurred at ICPs greater than 19 mm Hg and 24 mm Hg. Elastic net regression identified an ICP threshold of 19 mm Hg as most robustly associated with outcome when considering all neurocritical care patients, patients with TBI, and patients with TBI who underwent craniectomy. Intracranial pressure values greater than 19 mm Hg were associated with mortality, while lower values were associated with outcome in surviving patients. This study provides insight into what normal ICP values could be. An ICP threshold of 19 mm Hg was robustly associated with outcome in studied patients, although lower ICP values were associated with outcome in surviving patients.

Diseases of raised intracranial pressure (ICP) cause severe morbidity and mortality. Multiple drugs are utilised to lower ICP including acetazolamide and topiramate. However, the evidence for their use is unclear. We aimed to assess the ICP modulatory effects and molecular effects at the choroid plexus (CP) of acetazolamide and topiramate. Female rats were implanted with telemetric ICP probes for physiological, freely moving 24/7 ICP recordings. Randomised cross-over studies were performed, where rats received acute (24 h) high doses of acetazolamide and topiramate, and chronic (10days) clinically equivalent doses of acetazolamide and topiramate, all via oral gavage. Cerebrospinal fluid (CSF) secretion assays, and RT-qPCR and western blots on in vitro and in vivo CP, were used to investigate drug actions. We demonstrate that acetazolamide and topiramate achieved maximal ICP reduction within 120 min of administration, and in combination doubled the ICP reduction over a 24-h period. Chronic administration of acetazolamide or topiramate lowered ICP by 25%. Topiramate decreased CSF secretion by 40%. Chronic topiramate increased the gene expression of Slc12a2 and Slc4a10 and protein expression of the sodium-dependent chloride/bicarbonate exchanger (NCBE), whereas chronic acetazolamide did not affect the expression of assessed genes. Acetazolamide and topiramate are effective at lowering ICP at therapeutic levels. We provide the first evidence that topiramate lowers CSF secretion and that acetazolamide and topiramate may lower ICP via distinct molecular mechanisms. Thus, the combination of acetazolamide and topiramate may have utility for treating raised ICP.

An increasing number of studies indicate that the optic nerve head of the eye is sensitive not only to changes in intraocular pressure (IOP), but also to intracranial pressure (ICP). This study examines changes to optic nerve and retinal structure in a rat model in response to a range of IOP and ICP levels using optical coherence tomography. Furthermore, we examine the functional sequelae of these structural changes by quantifying the effect of pressure changes on the electroretinogram. IOP elevation (10–90 mmHg) induces progressive deformation of the optic nerve head and retinal surface (P < 0.05), compression of the retina (P < 0.05) and bipolar cell (b-wave), and retinal ganglion cell (scotopic threshold response) dysfunction (P < 0.05). Simultaneously altering ICP (−5 to 30 mmHg) modifies these IOP-induced responses, with lower ICP (−5 mmHg) exacerbating and higher ICP (15–30 mmHg) ameliorating structural and functional deficits. Thus, the balance between IOP and ICP (optic nerve pressure gradient, ONPG = IOP − ICP) plays an important role in optic nerve integrity. Structural and functional parameters exhibit a two-phase relationship to ONPG, with structural changes being more sensitive to ONPG modification (threshold = −0.6 to 11.3 mmHg) compared with functional changes (threshold = 49.7–54.6 mmHg). These findings have implications for diseases including glaucoma, intracranial hypertension, and long-term exposure to microgravity.

Elevated intracranial pressure (ICP) is a common clinical condition in critically ill patients with neurological injuries such as traumatic brain injury, intracerebral hemorrhage, and acute ischemic stroke. Elevated ICP is often caused by cerebral edema, a swelling of the brain that is largely dependent on primary pathology and intracellular changes.1 The Monro-Kellie doctrine states that the sum of volumes of cerebrospinal fluid, brain, and blood is constant and that an increase in any of the intracranial compartments should be balanced by a decrease in the other components. As the skull is an inflexible, enclosed space, inability to achieve pressure-volume equilibrium results in intracranial hypertension and ischemia. The normal adult ICP ranges from 5 to 15 mm Hg, and an ICP greater than 20 mm Hg indicates intracranial hypertension requiring treatment.2 Elevated ICP is associated with worse clinical outcomes; therefore, appropriate treatment should be initiated immediately.1Options for the treatment of intracranial hypertension include sedation, neuromuscular blockade, hyperventilation, hyperosmolar therapy, hypothermia, and surgical decompression. Hyperosmolar therapy is one of the most commonly employed strategies for reducing ICP by targeting cerebral edema and creating an osmotic gradient that decreases intracranial water content. Currently, mannitol and hypertonic saline (HTS) are the most studied and widely used hyperosmolar agents. Understanding the characteristics of these hyperosmolar agents is critical to ensure the efficacy and safety of therapy. Additionally, new literature evaluating the relative effectiveness of mannitol and HTS has become available in recent years. This review provides an overview of hyperosmolar therapy, with a focus on mannitol and HTS, for the management of intracranial hypertension.Mannitol works as a direct osmotic diuretic, reducing cerebrospinal fluid and brain water by creating an osmotic gradient across the blood-brain barrier (BBB). Redistribution of cerebral plasma volume results in cerebral vasoconstriction and decreased ICP. It also transiently increases cerebral blood flow by decreasing blood viscosity. Mannitol has a reflection coefficient of 0.9, indicating near impermeability to passive membrane transport across the BBB. Although mannitol is not completely excluded from passive transport, this high reflection coefficient contributes to its mechanism of action in drawing water from brain tissue into the vasculature.3 Reduction in ICP occurs rather rapidly, within 15 to 30 minutes of administration, and lasts for 1.5 to 6 hours. Typical dosing of mannitol for reduction of ICP is 0.5 to 1.5 g/kg of body weight, although doses up to 2 g/kg have been evaluated.4,5 Commercially, mannitol is available in 20% intravenous infusion bags and 25% intravenous injection vials.Mannitol therapy warrants additional considerations in administration. Mannitol is typically given as a bolus dose over 5 to 20 minutes rather than continuous infusion to avoid rebound elevation in ICP associated with prolonged therapy.6 At low temperatures, mannitol tends to form crystals. Before administration, mannitol solution must be carefully examined, and it should not be administered if crystals are observed. Instead, the container can be warmed to dissolve precipitates. A 0.22-μm in-line filter must be used when infusing mannitol to avoid the accidental injection of crystals.7 Although administration via central catheter was typically suggested in the past, evidence for the risk of extravasation with mannitol is not well reported in the literature. A recent retrospective study by Mesghali et al8 reported no incidences of extravasation among patients receiving mannitol via peripheral catheters. Considering the urgent nature of hyperosmolar therapy, clinicians may safely administer mannitol through a peripheral intravenous catheter, especially in the emergency department and intensive care unit.Despite its effectiveness and wide utilization in the reduction of ICP, mannitol is associated with several adverse events. Upon intravenous administration, mannitol remains primarily in the extracellular space and then is rapidly excreted through the kidneys, with less than 10% of the dose being reabsorbed.7,9 Therefore, in patients with preexisting renal impairment, mannitol can quickly accumulate in the circulation and may precipitate acute kidney injury (AKI). Excessive diuresis can also lead to decreased renal perfusion, contributing to worsening AKI.9 Mannitol is associated with both hypervolemia and hypovolemia. At first, mannitol rapidly expands intravascular volume by increasing serum osmolarity. Volume overload increases the risk of pulmonary edema or acute decompensated heart failure in high-risk patients.5,9 Subsequently, mannitol exerts its potent diuretic effects by rapidly removing intravascular volume, resulting in hypovolemia and hypotension. Excessive loss of water and electrolytes, in addition to AKI, leads to electrolyte imbalances, including hypokalemia or hyperkalemia, hyponatremia or hypernatremia, and hypochloremia.9 Perhaps the most troublesome complication associated with mannitol administration is rebound elevation in ICP. As indicated in its reflection coefficient, mannitol is not entirely impermeable to the BBB. When mannitol molecules cross the BBB, the osmotic gradient has the potential to pull water into the brain, resulting in rebound cerebral edema and elevation of ICP.2,6,9 The risk of adverse events increases when mannitol is administered for an extended period. Therefore, careful monitoring and tapering of the treatment are necessary to avoid such complications.To recognize potential adverse events associated with mannitol administration, clinicians must be vigilant in monitoring. Serum osmolarity and osmolar gap have been used to predict the risk of AKI in patients receiving mannitol therapy. Serum osmolarity exceeding 320 mOsm/L and an osmolar gap of 20 mOsm/kg or greater are reported to be associated with nephrotoxicity, although the evidence is limited.1,2,6,9 The Neurocritical Care Society guidelines on the management of cerebral edema recommend monitoring osmolar gap instead of serum osmolarity to avoid AKI development; however, the guidelines do not define a specific threshold because of insufficient evidence.1 In addition, vital signs, renal function, and electrolytes should be monitored frequently to identify potential hypotension, renal impairment, and electrolyte disturbances.Hypertonic saline is another osmotherapeutic agent commonly used to manage increased ICP and cerebral edema in various neurologic disease states. Although multiple mechanisms have been proposed, HTS is currently thought to reduce ICP through its osmotic effects. The osmotic gradient draws water from the interstitial and intracellular compartments of the brain into the intravascular space. Ultimately, reduction of brain water content results in decreased ICP.10 Unlike mannitol, HTS has a reflection coefficient of 1, indicating a complete exclusion to passive movement across the BBB. This reflection coefficient is a theoretical benefit of HTS over mannitol in terms of efficacy and reduced rate of rebound cerebral edema.3,10,11 In addition, HTS has a rheologic effect through a reduction in blood viscosity and compensatory vasoconstriction as well as other mechanisms involving dehydration of cerebrovascular endothelial cells, immunomodulatory effects, and neuroendocrine effects.10 Hypertonic saline has been shown to have a similar onset of action to mannitol in reducing ICP and may provide a continuous reduction in ICP for a duration commonly lasting up to 4 to 6 hours.12 In contrast to mannitol’s osmotic diuresis effect and risk of hypovolemia, HTS increases intravascular volume and may augment cardiac output. Because of this intravascular expansion, caution should be employed when administering HTS to patients with decompensated heart failure or pulmonary edema.13Hypertonic saline is available in a wide array of concentrations, most commonly ranging from 3% to 23.4%. It is most often provided as a chloride-rich solution, although some institutions have used buffered solutions containing sodium acetate or have even used hypertonic sodium bicarbonate in select scenarios.14,15 Because of a lack of evidence supporting an optimal protocol for use, dosing and administration of HTS can vary according to concentration and institutional practice. Typically, it is administered via intermittent bolus (eg, 2.5-5 mL/kg of 3% HTS over 5-20 minutes or 30 mL of 23.4% HTS over 10-20 minutes) or as a continuous intravenous infusion titrated to a goal serum sodium range.13The optimal method of HTS administration remains an area of uncertainty. Traditionally, the use of a central catheter to administer HTS solutions has been recommended to limit injury at the administration site. However, numerous publications have described safe administration of 3% HTS solutions via a peripheral catheter with appropriate monitoring. One retrospective study showed the potential safety of administering boluses of up to 5% HTS solutions peripherally for a limited duration.16,17 Additionally, a recent retrospective study showed that peripheral administration of 23.4% HTS was safe and achieved a reduction in ICP equivalent to that of central administration when used in emergency scenarios. This study found an overall low rate of administration-related adverse events in both the central and peripheral administration groups. This was the first publication documenting the safe use of 23.4% HTS via peripheral catheter.18 Close monitoring should be incorporated when administering HTS peripherally, and the infusion should be stopped if intravenous infiltration occurs.13In a direct comparison of continuous versus bolus doses of 3% HTS for the control of ICP elevation in patients with traumatic brain injury, Maguigan et al19 found no significant differences in cerebral perfusion pressure, ICP, length of stay, mortality, or time to goal osmolality between groups. However, a higher percentage of patients in the continuous infusion group than in the bolus group reached goal osmolality (93.9% vs 73.3%, P = .003).19 In a recent randomized controlled trial in patients with traumatic brain injury, continuous infusion of 20% HTS did not result in significantly better neurologic outcomes at 6 months compared with standard care, according to Extended Glasgow Outcome Scale scores (adjusted common odds ratio, 1.02; 95% CI, 0.71-1.47; P = .92).20 Current Neurocritical Care Society guidelines state that insufficient evidence exists to support the use of continuous infusion of HTS for targeting serum sodium goals to improve neurologic outcomes; therefore, a bolus approach is favored.1 Despite these reports, institutions continue to administer HTS through both bolus and continuous infusion methods on the basis of institutional practice and protocols.Although HTS has been shown to be safe and effective in various patient populations, it carries the risk of several potential adverse effects because of its high osmolarity and significant sodium content. Adverse effects include pulmonary edema, acute heart failure, coagulopathy, extravasation injuries, hypernatremia, hypokalemia, metabolic acidosis, renal failure, and acute hypotension following rapid administration.21 Hypertonic saline has also been associated with the risk of osmotic demyelination syndrome with rapid sodium correction.21 In all patients receiving HTS, serum sodium concentrations should be monitored every 4 to 6 hours to guide dosing and allow for the use of the lowest effective dose possible. The serum sodium level should be assessed before HTS administration in patients receiving intermittent boluses.13 Current Neurocritical Care Society guidelines recommend limiting the upper range of serum sodium to 155 to 160 mEq/L and serum chloride to 110 to 115 mEq/L and monitoring renal function closely to decrease the risk of AKI.1 In patients with chronic hyponatremia, overcorrection of sodium should be avoided to prevent osmotic demyelination syndrome, a potentially fatal complication. Neurologic examinations, evaluations of vital signs and volume status, and monitoring of the intravenous access site should also be conducted regularly.13Although both HTS and mannitol have been used for some time, HTS has gained popularity in recent years as an accepted first-line option for the treatment of elevated ICP.3 Systematic reviews and meta-analyses have suggested that compared with mannitol, HTS has potential immediate benefits including duration of effect, difference in cerebral perfusion pressure, and brain relaxation during craniotomy.12,22 Additionally, limited data suggest that HTS may have a role in treating refractory intracranial hypertension and reducing the risk of treatment failure compared with mannitol.23,24 Despite these proposed benefits, the quality of evidence in current literature remains low because of significant study heterogeneity, and no differences between mannitol and HTS for improving long-term outcomes such as neurological function and mortality have been shown.25,26 On the basis of the low quality of evidence and lack of proven long-term benefit, current guidelines recommend using either mannitol or HTS to manage intracranial hypertension and cerebral edema, although the Neurocritical Care Society has given slight favor to HTS over mannitol for select disease states.1,4,27Because of the lack of clear superiority of one hyperosmolar agent over another, the selection of mannitol or HTS should be based on patient-specific factors and agent-specific adverse events when used to manage intracranial hypertension (Table). For example, mannitol should be avoided in patients with AKI because of its dose-dependent nephrotoxicity. The intravascular volume expansion provided by HTS may limit its use in patients at increased risk of fluid overload, such as those with decompensated heart failure or pulmonary edema. Additionally, HTS should be used cautiously in patients with chronic hyponatremia to reduce the risk of osmotic demyelination syndrome, whereas mannitol may have a higher likelihood of causing rebound ICP if used for prolonged periods of time. Regardless of selection, continued monitoring and assessment of the patient is of utmost importance to ensure the safe and effective use of hyperosmolar therapy.Hyperosmolar therapy is commonly used in the management of intracranial hypertension. Current literature comparing the safety and efficacy of hyperosmolar agents is heterogeneous and low quality at best. Despite certain theoretical benefits of one agent over the other, neither mannitol nor HTS has been proven to be more effective in improving long-term outcomes in patients requiring treatment for intracranial hypertension. Selection of the agent should be based on relevant patient factors and medication characteristics.

Elevation of intracranial pressure (ICP) may worsen brain injury and neurological outcome. Studies on the use of therapeutic hypothermia (TH) for traumatic brain injury suggests that rapid rewarming from TH is associated with elevated ICP and poorer outcomes. However, few studies describe the time course of ICP changes during TH/rewarming after cardiac arrest (CA). In this study, we observed the changes in ICP during mild TH and rewarming after CA. Secondarily, we examined whether ICP is related to outcome. We studied comatose patients resuscitated from CA, who were treated with TH and who had ICP monitored. Target core temperature was 34°C for 24 h and target rewarming rate was 0.25°C/h. ICP and cerebral perfusion pressure (CPP) were monitored during the period. Outcome was rated as cerebral performance category. In nine patients, ICP increased during TH and rewarming (6.0 [4.0-9.0] mmHg to 16.0 [12.0-26.0] mmHg, p = 0.008). CPP did not change during the period (83.3 [80.1-91.0] mmHg to 74.3 [52.0-87.3] mmHg). Higher ICP was associated with worse outcomes (p = 0.009). All the cases with ICP >25 mmHg or CPP <40 mmHg died. Major ICP increment was observed during the rewarming period, although, some increase of ICP occurred even during the mild TH. ICP increment was higher in patients with worse outcomes.

Numerous trials have addressed intracranial pressure (ICP) management in neurocritical care. However, identifying its harmful thresholds and controlling ICP remain challenging in terms of improving outcomes. Evidence suggests that an individualized approach is necessary for establishing tolerance limits for ICP, incorporating factors such as ICP waveform (ICPW) or pulse morphology along with additional data provided by other invasive (e.g., brain oximetry) and noninvasive monitoring (NIM) methods (e.g., transcranial Doppler, optic nerve sheath diameter ultrasound, and pupillometry). This study aims to assess current ICP monitoring practices among experienced clinicians and explore whether guidelines should incorporate ancillary parameters from NIM and ICPW in future updates. We conducted a survey among experienced professionals involved in researching and managing patients with severe injury across low-middle-income countries (LMICs) and high-income countries (HICs). We sought their insights on ICP monitoring, particularly focusing on the impact of NIM and ICPW in various clinical scenarios. From October to December 2023, 109 professionals from the Americas and Europe participated in the survey, evenly distributed between LMIC and HIC. When ICP ranged from 22 to 25 mm Hg, 62.3% of respondents were open to considering additional information, such as ICPW and other monitoring techniques, before adjusting therapy intensity levels. Moreover, 77% of respondents were inclined to reassess patients with ICP in the 18-22mm Hg range, potentially escalating therapy intensity levels with the support of ICPW and NIM. Differences emerged between LMIC and HIC participants, with more LMIC respondents preferring arterial blood pressure transducer leveling at the heart and endorsing the use of NIM techniques and ICPW as ancillary information. Experienced clinicians tend to personalize ICP management, emphasizing the importance of considering various monitoring techniques. ICPW and noninvasive techniques, particularly in LMIC settings, warrant further exploration and could potentially enhance individualized patient care. The study suggests updating guidelines to include these additional components for a more personalized approach to ICP management.

The use of barbiturates to induce coma as a means of extending the period of reversible cerebral ischemia is reviewed. Barbiturate use in patients who had had strokes or were undergoing aneurysm surgery was initially encouraging. In uncontrolled feasibility trials in patients with cardiopulmonary arrest or in deep coma, 40 patients received 10 mg/kg thiopental sodium by i.v. push followed by 20 mg/kg thiopental sodium i.v. over the next 30 minutes; 60% of these patients regained consciousness. In a subgroup of 22 patients who had ischemia normally associated with a 90% mortality rate, 14 recovered completely. In the largest clinical trial, 45 patients with severe head injury and elevated intracranial pressure received 3--5 mg/kg pentobarbital over 10--20 minutes. A serum barbiturate level of 2.5--4.0 mg/dl was maintained for 14 days, and 30% of these patients recovered but with neurologic deficits. Other results in stroke and drowning victims were not as encouraging. It is concluded that barbiturate therapy is beneficial in the lowering of intracranial pressure. Focal and global cerebral ischemia have been shown amenable to barbiturate therapy in isolated cases. The prophylactic use of barbiturates in surgical procedures requiring focal cerebral anoxia appears to be beneficial. Controlled trials of the use of barbiturate-induced coma are clearly indicated.

Intracranial pressure (ICP) is an important neurovascular vital sign and is tracked in a variety of conditions affecting the brain. Clinical decision-making is largely based on trends in mean ICP, although the pulsatile ICP waveform might also be harnessed to derive information about the physical characteristics of the brain tissue and cerebrospinal fluid compartment. In this investigation, we use small models of the cerebrospinal space to understand the morphology of the ICP waveform and to determine which cerebrospinal characteristics can be estimated from the ICP waveform. Intracranial pressure (ICP) is an important vital sign of the brain and is often measured continuously in patients in neurocritical care. While clinical decisions are primarily based on mean ICP, the pulsatile ICP waveform reflects physical characteristics of the cerebrospinal space that could be harnessed to provide additional information for clinical decision-making..