Intracranial Pressure Response Research Articles

Bilayer surrogate brain response under various blast loading conditions

AbstractVariations in the experimental constraints applied within blast simulations can result in dramatically different measured biomechanical responses. Ultimately, this limits the comparison of data between research groups and leads to further inquisitions about the “correct” biomechanics experienced in blast environments. A novel bilayer surrogate brain was exposed to blast waves generated from advanced blast simulators (ABSs) where detonation source, boundary conditions, and ABS geometry were varied. The surrogate was comprised of Sylgard 527 (1:1) as a gray matter simulant and Sylgard 527 (1:1.2) as a white matter simulant. The intracranial pressure response of this surrogate brain was measured in the frontal region under primary blast loading while suspended in a polyurethane spherical shell with 5 mm thickness and filled with water to represent the cerebrospinal fluid. Outcomes of this work discuss considerations for future experimental designs and aim to address sources of variability confounding interpretation of biomechanical responses.

Regional Strain Response of an Anatomically Accurate Human Finite Element Head Model Under Frontal Versus Lateral Loading.

Because brain regions are responsible for specific functions, regional damage may cause specific, predictable symptoms. However, the existing brain injury criteria focus on whole brain response. This study developed and validated a detailed human brain computational model with sufficient fidelity to include regional components and demonstrate its feasibility to obtain region-specific brain strains under selected loading. Model development used the Simulated Injury Monitor (SIMon) model as a baseline. Each SIMon solid element was split into 8, with each shell element split into 4. Anatomical regions were identified from FreeSurfer fsaverage neuroimaging template. Material properties were obtained from literature. The model was validated against experimental intracranial pressure, brain-skull displacement, and brain strain data. Model simulations used data from laboratory experiments with a rigid arm pendulum striking a helmeted head-neck system. Data from impact tests (6 m/s) at 2 helmet sites (front and left) were used. Model validation showed good agreement with intracranial pressure response, fair to good agreement with brain-skull displacement, and good agreement for brain strain. CORrelation Analysis scores were between 0.72 and 0.93 for both maximum principal strain (MPS) and shear strain. For frontal impacts, regional MPS was between 0.14 and 0.36 (average of left and right hemispheres). For lateral impacts, MPS was between 0.20 and 0.48 (left hemisphere) and between 0.22 and 0.51 (right hemisphere). For frontal impacts, regional cumulative strain damage measure (CSDM20) was between 0.01 and 0.87. For lateral impacts, CSDM20 was between 0.36 and 0.99 (left hemisphere) and between 0.09 and 0.93 (right hemisphere). Recognizing that neural functions are related to anatomical structures and most model-based injury metrics focus on whole brain response, this study developed an anatomically accurate human brain model to capture regional responses. Model validation was comparable with current models. The model provided sufficient anatomical detail to describe brain regional responses under different impact conditions.

Comparison of Biomechanical Outcome Measures From Characteristically Different Blast Simulators and the Influence of Exposure Location.

Simulation of blast exposure in the laboratory has been inconsistent across laboratories. This is primarily because of adoption of the shock wave-generation techniques that are used in aerodynamic tests as opposed to application of blast exposures that are relevant to combat and training environments of a Warfighter. Because of the differences in blast signatures, characteristically different pathological consequences are observed among the preclinical studies. This is also further confounded by the varied exposure positioning of the animal subject (e.g., inside the blast simulator vs. at the mouth of the simulator). In this study, we compare biomechanical responses to blast exposures created in an advanced blast simulator (ABS) that generates "free-field"-like blast exposure with those produced by a traditionally applied cylindrical blast simulator (CBS) that generates a characteristically different blast signature. In addition, we have tested soft-armor vest protective responses with the ABS and CBS to compare the biomechanical responses to this form of personal protective equipment in each setting in a rodent model. Anesthetized male Sprague-Dawley rats (n = 6) were surgically probed with an intrathoracic pressure (ITP) transducer and an intracranial pressure (ICP) transducer directed into the lateral cerebral ventricle (Millar, Inc.). An ABS for short-duration blast or a CBS for long-duration blast was used to expose animals to an incident blast overpressure of 14.14 psi (impulse: 30.27 psi*msec) or 16.3 psi (impulse: 71.9 psi*msec) using a custom-made holder (n = 3-4/group). An external pitot probe located near the animal was used to measure the total pressure (tip) and static gauge (side-on) pressure. Data were recorded using a TMX-18 data acquisition system (AstroNova Inc.). MATLAB was used to analyze the recordings to identify the peak amplitudes and rise times of the pressure traces. Peak ICP, peak ITP, and their impulses were normalized by expressing them relative to the associated peak static pressure. Normalized impulse (ABS: 1.02 ± 0.03 [vest] vs. 1.02 ± 0.01 [no-vest]; CBS: 1.21 ± 0.07 [vest] vs. 1.01 ± 0.01 [no-vest]) and peak pressure for ICP (ABS: 1.03 ± 0.03 [vest] vs. 0.99 ± 0.04 [no-vest]; CBS: 1.06 ± 0.08 [vest] vs. 1.13 ± 0.06 [no-vest]) remained unaltered when comparisons are made between vest and no-vest groups, and the normalized peak ITP (ABS: 1.50 ± 0.02 [vest] vs. 1.24 ± 0.16 [no-vest]; CBS: 1.71 ± 0.20 [vest] vs. 1.37 ± 0.06 [no-vest]) showed a trend of an increase in the vest group compared to the no-vest group. However, impulses in short-duration ABS (0.94 ± 0.06 [vest] vs. 0.92 ± 0.13 [no-vest]) blast remained unaltered, whereas a significant increase of ITP impulse (1.21 ± 0.07 [vest] vs. 1.17 ± 0.01 [no-vest]) in CBS was observed. The differences in the biomechanical response between ABS and CBS could be potentially attributed to the higher dynamic pressures that are imparted from long-duration CBS blasts, which could lead to chest compression and rapid acceleration/deceleration. In addition, ICP and ITP responses occur independently of each other, with no evidence of thoracic surge.

The effect of increased positive end expiratory pressure on brain tissue oxygenation and intracranial pressure in acute brain injury patients

Cerebral hypoxia is an important cause of secondary brain injury. Improving systemic oxygenation may increase brain tissue oxygenation (PbtO2). The effects of increased positive end-expiratory pressure (PEEP) on PbtO2 and intracranial pressure (ICP) needs to be further elucidated. This is a single center retrospective cohort study (2016–2021) conducted in a 34-bed Department of Intensive Care unit. All patients with acute brain injury under mechanical ventilation who were monitored with intracranial pressure and brain tissue oxygenation (PbtO2) catheters and underwent at least one PEEP increment were included in the study. Primary outcome was the rate of PbtO2 responders (increase in PbtO2 > 20% of baseline) after PEEP increase. ΔPEEP was defined as the difference between PEEP at 1 h and PEEP at baseline; similarly ΔPbtO2 was defined as the difference between PbtO2 at 1 h after PEEP incrementation and PbtO2 at baseline. We included 112 patients who underwent 295 episodes of PEEP increase. Overall, the median PEEP increased form 6 (IQR 5–8) to 10 (IQR 8–12) cmH2O (p = 0.001), the median PbtO2 increased from 21 (IQR 16–29) mmHg to 23 (IQR 18–30) mmHg (p = 0.001), while ICP remained unchanged [from 12 (7–18) mmHg to 12 (7–17) mmHg; p = 0.42]. Of 163 episode of PEEP increments with concomitant PbtO2 monitoring, 34 (21%) were PbtO2 responders. A lower baseline PbtO2 (OR 0.83 [0.73–0.96)]) was associated with the probability of being responder. ICP increased in 142/295 episodes of PEEP increments (58%); no baseline variable was able to identify this response. In PbtO2 responders there was a moderate positive correlation between ΔPbtO2 and ΔPEEP (r = 0.459 [95% CI 0.133–0.696]. The response in PbtO2 and ICP to PEEP elevations in brain injury patients is highly variable. Lower PbtO2 values at baseline could predict a significant increase in brain oxygenation after PEEP increase.

Effects of caffeine on intracranial pressure and pain perception in freely moving rats.

Caffeine, a non-selective adenosine receptor (AR) antagonist, is the most consumed psychostimulant in the world. Caffeine has been suggested to regulate cerebrospinal fluid secretion and is known both to alleviate and to trigger headache; however, its effect on the regulation of intracranial pressure (ICP) is not known. Therefore, we aimed to investigate the effects of caffeine on ICP and nociceptive responses. Female Sprague-Dawley rats were implanted with a novel telemetric device for continuous ICP recordings, which allowed for continuous recordings in freely moving rats. A single dose of caffeine (30 or 120 mg/kg intraperitoneally) was given. In a second group (non-implanted), the acute effects of 30 mg/kg caffeine on periorbital threshold using Von Frey testing and spontaneous behavior were utilized using an automated behavioral registration platform (Laboratory, Animal, Behavior, Observation, Registration and Analysis System) in a randomized cross-over study. Quantitative polymerase chain reaction and immunofluorescence were used to localize ARs in the choroid plexus. A single dose of 30 mg/kg caffeine lowered the ICP by 35% at 165 min after administration (saline: 0.16 ± 0.9 vs caffeine: -1.18 ± 0.9 ΔmmHg, p = 0.0098) and lasted up to 12 h. Administration of 120 mg/kg caffeine showed a faster onset of decrease in ICP within 15 min by 50% (p = 0.0018) and lasted up to 12 h. The periorbital pain thresholds were higher after 1 h (saline: 224.6 ± 15.1 vs caffeine: 289.5 ± 8.7 g, p = 0.005) and lasted up to 5 h. Caffeine-treated rats had increased locomotor activity, speed, and changed grooming behavior. Expression of AR1 was found in the choroid plexus. This study demonstrates that caffeine has a lowering effect on ICP as an acute treatment. Interestingly, caffeine acutely caused an increased response in cephalic thresholds supporting hypoalgesic effects. Future studies investigating the beneficial effects of caffeine for elevated ICP are warranted.

Intracranial pressure measurement under shock wave based on physical head surrogate

In order to explore the intracranial pressure response under different sensor fixation modes, the experimental study on the pressure measurement based on physical head surrogate under shock wave is carried out. The influence of different sensor fixation methods on the intracranial pressure was analyzed. The results show that sensor fixation mode has little influence on the pressure test results. The deviation between the pressure peak and impulse is only 3.62% and 4.54% in the two modes of hot melt supporting and free suspension. The deviation of pressure peak value between metal supporting and free suspension is 5.59%. In comparison, hot melt supporting fixation has less influence on intracranial pressure results. The orientation of sensor sensitive surface has little influence on the pressure test results. When sensor was fixed by the metal bracket, the deviation of pressure peak is only 4.03% between sensitive surface face to impact source and sensitive surface back to shock source.

Publisher Correction: Evaluating the Intracranial Pressure Biofidelity and Response Repeatability of a Physical Head-Brain Model in Frontal Impacts

Publisher Correction: Evaluating the Intracranial Pressure Biofidelity and Response Repeatability of a Physical Head-Brain Model in Frontal Impacts

Evaluating the Intracranial Pressure Biofidelity and Response Repeatability of a Physical Head-Brain Model in Frontal Impacts.

Headforms are widely used in head injury research and headgear assessment. Common headforms are limited to replicating global head kinematics, although intracranial responses are crucial to understanding brain injuries. This study aimed to evaluate the biofidelity of intracranial pressure (ICP) and the repeatability of head kinematics and ICP of an advanced headform subjected to frontal impacts. Pendulum impacts were performed on the headform using various impact velocities (1-5m/s) and impactor surfaces (vinyl nitrile 600 foam, PCM746 urethane, and steel) to simulate a previous cadaveric experiment. Head linear accelerations and angular rates in three axes, cerebrospinal fluid ICP (CSFP), and intraparenchymal ICP (IPP) at the front, side, and back of the head were measured. The head kinematics, CSFP, and IPP demonstrated acceptable repeatability with coefficients of variation generally being less than 10%. The BIPED front CSFP peaks and back negative peaks were within the range of the scaled cadaver data(between the minimum and maximum values reported by Nahum et al.), while side CSFPs were 30.9-92.1% greater than the cadaver data. CORrelation and Analysis (CORA) ratings evaluating the closeness of two time histories demonstrated good biofidelity of the front CSFP (0.68-0.72), while the ratings for the side (0.44-0.70) and back CSFP (0.27-0.66) showed a large variation. The BIPED CSFP at each side was linearly related to head linear accelerations with coefficients of determination greater than 0.96. The slopes for the BIPED front and back CSFP-acceleration linear trendlines were not significantly different from cadaver data, whereas the slope for the side CSFP was significantly greater than cadaver data. This study informs future applications and improvements of a novel head surrogate.

Relationship between edema and intracranial pressure following intracerebral hemorrhage in rat

Elevated intracranial pressure (ICP) is a potentially fatal consequence of intracerebral hemorrhage (ICH). As the mass of the hematoma and regional edema builds, ICP rises and becomes increasingly variable acutely after stroke. High ICP may worsen cellular injury and edema by impairing local tissue perfusion, fueling a cycle that may ultimately cause fatality through ischemia and brain herniation. Time spent above an ICP of 20 mmHg often predicts a greater risk of death and disability following ICH. Compensatory mechanisms combat rising ICP. Classically, these include cerebrospinal fluid volume loss and cerebrovascular autoregulation, such as a reduction in the volume of venous blood. Additional mechanisms such as brain tissue compliance and skull volume compensation may also contribute. Compensatory compliance mechanisms are limited, and they vary by age and many other factors. Animal models of ICH are widely used to assess these variables and to gauge putative therapeutics. Most often those studies rely upon simple measures of edema, which may not accurately predict ICP data. Thus, we analyzed our past studies characterizing ICP, edema, and tissue compliance responses to striatal ICH in rat, including the collagenase (C-ICH) and whole blood models (WB-ICH). We found that both ICH models raised ICP, with greater effects in the C-ICH model, which may thus better reflect clinical findings of concern. Importantly, measures of edema, such as in the damaged hemisphere, on their own are not predictive of average or peak ICP response within either model, unless assessing across a very wide range of injury severities, or when including non-stroke animals. We caution against using edema data as a surrogate measure of mass effect and ICP following ICH.

Beyond intracranial pressure: monitoring cerebral perfusion and autoregulation in severe traumatic brain injury.

Severe traumatic brain injury (TBI) remains the most prevalent neurological condition worldwide. Observational and interventional studies provide evidence to recommend monitoring of intracranial pressure (ICP) in all severe TBI patients. Existing guidelines focus on treating elevated ICP and optimizing cerebral perfusion pressure (CPP), according to fixed universal thresholds. However, both ICP and CPP, their target thresholds, and their interaction, need to be interpreted in a broader picture of cerebral autoregulation, the natural capacity to adjust cerebrovascular resistance to preserve cerebral blood flow in response to external stimuli. Cerebral autoregulation is often impaired in TBI patients, and monitoring cerebral autoregulation might be useful to develop personalized therapy rather than treatment of one size fits all thresholds and guidelines based on unidimensional static relationships. Today, there is no gold standard available to estimate cerebral autoregulation. Cerebral autoregulation can be triggered by performing a mean arterial pressure (MAP) challenge, in which MAP is increased by 10% for 20 min. The response of ICP (increase or decrease) will estimate the status of cerebral autoregulation and can steer therapy mainly concerning optimizing patient-specific CPP. The role of cerebral metabolic changes and its relationship to cerebral autoregulation is still unclear and awaits further investigation.

Wearable Sensing System for NonInvasive Monitoring of Intracranial BioFluid Shifts in Aerospace Applications

The alteration of the hydrostatic pressure gradient in the human body has been associated with changes in human physiology, including abnormal blood flow, syncope, and visual impairment. The focus of this study was to evaluate changes in the resonant frequency of a wearable electromagnetic resonant skin patch sensor during simulated physiological changes observed in aerospace applications. Simulated microgravity was induced in eight healthy human participants (n = 8), and the implementation of lower body negative pressure (LBNP) countermeasures was induced in four healthy human participants (n = 4). The average shift in resonant frequency was -13.76 ± 6.49 MHz for simulated microgravity with a shift in intracranial pressure (ICP) of 9.53 ± 1.32 mmHg, and a shift of 8.80 ± 5.2097 MHz for LBNP with a shift in ICP of approximately -5.83 ± 2.76 mmHg. The constructed regression model to explain the variance in shifts in ICP using the shifts in resonant frequency (R2 = 0.97) resulted in a root mean square error of 1.24. This work demonstrates a strong correlation between sensor signal response and shifts in ICP. Furthermore, this study establishes a foundation for future work integrating wearable sensors with alert systems and countermeasure recommendations for pilots and astronauts.

Optic nerve sheath diameter correlates to intracranial pressure in spontaneous CSF leak patients.

Spontaneous cerebrospinal fluid (sCSF) leaks develop from pressure erosion due to idiopathic intracranial hypertension, treatment of which is paramount to preventing recurrence. Direct measurements of intracranial pressure (ICP) for monitoring response to treatment via lumbar drain (LD) or ventriculostomy are invasive and have risks. The objectives of this study are to determine whether ultrasonographic measurements of optic nerve sheath diameter (ONSD) correlate with LD ICP in patients with sCSF leaks undergoing treatment, and whether ONSDs are larger in patients with sCSF leaks than controls. Subjects with sCSF leaks and controls were prospectively recruited. ONSD, sex, and body mass index (BMI) were analyzed. For sCSF leak subjects, ultrasonography was performed at the time of LD opening and each pressure check postoperatively, including the acetazolamide response. In control patients, measurements were obtained at the time of surgery. Pearson's correlation between ONSD and ICP was performed. Subjects with sCSF leaks (n=9, age 52.4±9.5, all female) and controls (n=8, age 60.1±14.8, two females) had significantly different BMIs, 38.4±8.1 vs. 29.2±4.8, t(15)=2.793, p=0.014. ONSD was strongly correlated with ICP measurements (r=0.583, p=0.002). However, percentage change in ONSD and ICP measurements were more strongly correlated (r=0.733, p<0.001). Patients with sCSF leaks had significantly higher ONSDs than controls, 0.63cm±0.044 vs. 0.56cm±0.074, t(15)=2.329, p=0.034. ONSD significantly correlated with ICP in sCSF leak patients and was wider in sCSF leak subjects than controls. Ultrasonography has utility in monitoring the ICP response to acetazolamide.

Intravenous lidocaine attenuates distention of the optical nerve sheath, a correlate of intracranial pressure, during endotracheal intubation.

By preventing hypoxia and hypercapnia, advanced airway management can save lives among patients with traumatic brain injury. During endotracheal intubation (ETI), tracheal stimulation causes an increase in intracranial pressure (ICP), which may impair brain perfusion. It has been suggested that intravenous lidocaine might attenuate this ICP response. We hypothesized that adding lidocaine to the standard induction medication for general anesthesia might reduce the ICP response to ETI. Here, we measured the optical nerve sheath diameter (ONSD) as a correlate of ICP and evaluated the effect of intravenous lidocaine on ONSD during and after ETI in patients undergoing anesthesia. This double-blinded, randomized placebo-controlled trial included 60 patients with American Society of Anesthesiologists I or II physical status that were scheduled for elective surgery under general anesthesia. In addition to the standard anesthesia medication, 30 subjects received 1.5 mg/kg 1% lidocaine (0.15 mL/kg, ONSD<inf>lidocaine</inf>) and 30 received 0.15 mL/kg 0.9% NaCl (ONSD<inf>placebo</inf>). ONSDs were measured with ultrasound on the left eye, before (T<inf>0</inf>), during (T<inf>1</inf>), and 4 times after ETI (T<inf>2-5</inf> at 5-min intervals). Compared to placebo, lidocaine did not significantly affect the baseline ONSD after anesthesia induction measured at T<inf>0</inf>. During ETI, the ONSD<inf>lidocaine</inf> was significantly smaller (β=-0.24 mm P=0.022) than the ONSD<inf>placebo</inf>. At T<inf>4</inf> and T<inf>5</inf>, the ONSD<inf>placebo</inf> increased steadily, up to 20 min after ETI, but the ONSD<inf>lidocaine</inf> tended to return to baseline levels. We found that the ONSD was distended during and after ETI in anesthetized patients, and intravenous lidocaine attenuated this effect.

Experimental Study on Intracranial Pressure and Biomechanical Response in Rats Under the Blast Wave.

Explosion overpressure propagates extracranially and causes craniocerebral injury after being transmitted into the brain. Studies on the extent of skull to reduce impact overpressure are still lacking. Therefore, it is necessary to study the relationship between intracranial pressure (ICP) and external field pressure and the situation of craniocerebral injury under the blast wave. Pressure sensor of 1.2 mm was disposed 3 mm posterior to the bregma of rat skull, and type I biological shock tube (BST-I) was used as the source of injury while a side-on air pressure sensor was installed at the horizontal position of the ICP sensor. Eleven groups of blast experiments with peak air overpressure ranging from 167 kPa to 482 kPa were performed to obtain the variation law of ICP and injury of rats. Data measured by sensors show that the peak pressure formed in the rat brain are lower than the external air overpressure; the differential pressure between the inside and outside of the brain is 27-231 kPa. When side-on air overpressure is ≤363 kPa, ICP is ≤132 kPa, and the hemorrhage area of the rat's brain is <15%, the injury is minor. When side-on air overpressure is 363 kPa-401 kPa, ICP range is from 132 kPa to 248 kPa, hemorrhage area is about 15%-20%, and the injury increases. When side-on air overpressure is 401 kPa-435 kPa, ICP range from 248 kPa to 348 kPa, the hemorrhage area is about 20%-24%, and the injury is serious. When side-on air overpressure ≥482 kPa, the peak ICP surged to 455 kPa and the peak negative ICP reached -84 kPa, the hemorrhage area exceeded 26%. When the external blast wave is weak, skull can absorb the blast wave better, reducing the pressure by 81.4%, when the external shockwave is strong, skull only reduces the pressure by 5.6%, but both can play certain protective role. The fitting curve of air overpressure and ICP can be used to predict the changes of ICP under different external blast overpressure. Analysis of cranial injury showed that the area of cranial hemorrhage with extremely severe injury increased by 107.9% compared with mild injury, increased by 53.3% compared with moderate injury, and increased by 21.6% compared with severe injury. This work may provide references for the dynamic response of biological cranial and brain injury mechanism under the effect of blast wave.

Pressure-Volume Relationships in the Spinal Canal and Potential Neurological Complications After Epidural Fluid Injections.

High-volume fluid injections into the spinal canal may lead to severe neurological complications. But when anatomical or pathological conditions in the spinal canal are unfavorable, even small volume epidural injections can cause dangerously high epidural, subarachnoid, and intracranial pressures or pressure gradients. Data obtained from the scientific literature and direct clinical observation are used to derive a first-order approximation of epidural, subarachnoid, and intracranial pressure responses to epidural fluid injections. Maximum allowable fluid volumes for single or multiple divided fluid injections over time are calculated. In the presence of spinal pathology, 10 ml of fluids may increase epidural pressure to >100 mmHg. Injection speed >4 ml per second may also generate dangerously high intraspinal and intracranial pressures. Intermitted bolus injections provide limited protection, but intraspinal pressures may rise very fast when a critical total injected volume is reached. Potential complications of increased intracranial pressures or large pressure waves include nerve palsies, tinnitus, blindness, stroke, and death. Spinal injections or endoscopy should be performed in an awake responsive patient or with direct cerebrospinal fluid pressure monitoring. A set of guidelines for epidural fluid management is given.

Abstract 272: Identifying Vascular Determinants Of Optimal Cerebral Perfusion Pressure In Traumatic Brain Injury Using A Continuous Measurement Algorithm.

Introduction: Individualized therapy targeting certain cerebral perfusion pressure (CPP) values in patients with traumatic brain injury may improve outcomes. One method to obtain “optimal” CPP (CPPopt) uses a measurement algorithm with continuous arterial blood pressure (ABP) and intracranial pressure (ICP) to estimate CPPopt where the pressure reactivity index is lowest. Yet, there is a knowledge gap regarding the cerebrovascular conditions that determine the algorithm’s success and validity. Here, we use a validated brain vasculature model to assess the algorithm’s performance at varying simulated vascular conditions. Methods: We used a convenience sample of 12 patient records with 4 hours of high-resolution ABP from the MIMIC III database. Each ABP set generated a synthetic ICP from our model. The algorithm then performed 38,815 CPPopt estimates across 12 patient records based on given input parameters. We examined “G”, an autoregulation parameter representing the sensitivity of ICP response to ABP change, and “Tau”, a time parameter representing the delay in ICP response to ABP change. We varied G and Tau independently and measured changes in frequency of algorithm success in finding CPPopt (CPPopt coverage), pressure reactivity index (PRx), and CPPopt itself. Results: 1.As G increases, CPPopt coverage, and mean minimum PRx decrease.2.As Tau increases, CPPopt coverage, and mean minimum PRx increase.3.CPPopt coverage had a median success rate of 27.111% and IQR of 29.118% across G and median success rate of 45.166% and IQR of 35.3362% across Tau for 38,815 algorithm estimates across the 12 patient records. Conclusion: The CPPopt algorithm may have a higher likelihood of finding CPPopt in pathological conditions where G is expected to be low and Tau to be large. The low and variable algorithm success rate poses a challenge for clinical use. More work is needed to understand the algorithm’s success and validity to determine its clinical viability.

Dual Orexin Receptor Antagonist Attenuates Increases in IOP, ICP, and Translaminar Pressure Difference After Stimulation of the Hypothalamus in Rats.

PurposeIntraocular pressure (IOP) remains the only modifiable risk factor for glaucoma progression. Our previous discovery that stimulation of nuclei within the hypothalamus can modulate IOP, intracranial pressure (ICP), and translaminar pressure difference (TLPD) fluctuations led us to investigate this pathway further. Our purpose was to determine the role of orexin neurons, primarily located in the dorsomedial hypothalamus (DMH) and perifornical (PeF) regions of the hypothalamus, in modulating these pressures.MethodsSprague Dawley rats were pretreated systemically with a dual orexin receptor antagonist (DORA-12) at 30 mg/Kg (n = 8), 10 mg/Kg (n = 8), or vehicle control (n = 8). The IOP, ICP, heart rate (HR), and mean arterial pressure (MAP) were recorded prior to and following excitation of the DMH/PeF using microinjection of the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline methiodide (BMI).ResultsAdministration of the DORA at 30 mg/Kg significantly attenuated peak IOP by 5.2 ± 3.6 mm Hg (P = 0.007). During the peak response period (8–40 minutes), the area under the curve (AUC) for the 30 mg/Kg DORA cohort was significantly lower than the control cohort during the same period (P = 0.04). IOP responses for peak AUC versus DORA dose, from 0 to 30 mg/Kg, were linear (R2 = 0.18, P = 0.04). The ICP responses during the peak response period (4–16 minutes) versus DORA dose were also linear (R2 = 0.24, P = 0.014). Pretreatment with DORA significantly decreased AUC for the TLPD following stimulation of the DMH/PeF (10 mg/kg, P = 0.045 and 30 mg/kg, P = 0.015).ConclusionsDORAs have the potential to attenuate asynchronous changes in IOP and in ICP and to lessen the extent of TLPDs that may result from central nervous system (CNS) activation.

Effects of positive end-expiratory pressure on lung ultrasound patterns and their correlation with intracranial pressure in mechanically ventilated brain injured patients

BackgroundThe effects of positive end-expiratory pressure (PEEP) on lung ultrasound (LUS) patterns, and their relationship with intracranial pressure (ICP) in brain injured patients have not been completely clarified. The primary aim of this study was to assess the effect of two levels of PEEP (5 and 15 cmH2O) on global (LUStot) and regional (anterior, lateral, and posterior areas) LUS scores and their correlation with changes of invasive ICP. Secondary aims included: the evaluation of the effect of PEEP on respiratory mechanics, arterial partial pressure of carbon dioxide (PaCO2) and hemodynamics; the correlation between changes in ICP and LUS as well as respiratory parameters; the identification of factors at baseline as potential predictors of ICP response to higher PEEP.MethodsProspective, observational study including adult mechanically ventilated patients with acute brain injury requiring invasive ICP. Total and regional LUS scores, ICP, respiratory mechanics, and arterial blood gases values were analyzed at PEEP 5 and 15 cmH2O.ResultsThirty patients were included; 19 of them (63.3%) were male, with median age of 65 years [interquartile range (IQR) = 66.7–76.0]. PEEP from 5 to 15 cmH2O reduced LUS score in the posterior regions (LUSp, median value from 7 [5–8] to 4.5 [3.7–6], p = 0.002). Changes in ICP were significantly correlated with changes in LUStot (rho = 0.631, p = 0.0002), LUSp (rho = 0.663, p < 0.0001), respiratory system compliance (rho = − 0.599, p < 0.0001), mean arterial pressure (rho = − 0.833, p < 0.0001) and PaCO2 (rho = 0.819, p < 0.0001). Baseline LUStot score predicted the increase of ICP with PEEP.ConclusionsLUS-together with the evaluation of respiratory and clinical variables-can assist the clinicians in the bedside assessment and prediction of the effect of PEEP on ICP in patients with acute brain injury.

Effects of Positive End-Expiratory Pressure on Lung Recruitment, Respiratory Mechanics, and Intracranial Pressure in Mechanically Ventilated Brain-Injured Patients.

Background: The pathophysiological effects of positive end-expiratory pressure (PEEP) on respiratory mechanics, lung recruitment, and intracranial pressure (ICP) in acute brain-injured patients have not been completely elucidated. The primary aim of this study was to assess the effects of PEEP augmentation on respiratory mechanics, quantitative computed lung tomography (qCT) findings, and its relationship with ICP modifications. Secondary aims included the assessment of the correlations between different factors (respiratory mechanics and qCT features) with the changes of ICP and how these factors at baseline may predict ICP response after greater PEEP levels.Methods: A prospective, observational study included mechanically ventilated patients with acute brain injury requiring invasive ICP and who underwent two-PEEP levels lung CT scan. Respiratory system compliance (Crs), arterial partial pressure of carbon dioxide (PaCO2), mean arterial pressure (MAP), data from qCT and ICP were obtained at PEEP 5 and 15 cmH2O.Results: Sixteen examinations (double PEEP lung CT and neuromonitoring) in 15 patients were analyzed. The median age of the patients was 54 years (interquartile range, IQR = 39–65) and 53% were men. The median Glasgow Coma Scale (GCS) at intensive care unit (ICU) admission was 8 (IQR = 3–12). Median alveolar recruitment was 2.5% of total lung weight (−1.5 to 4.7). PEEP from 5 to 15 cmH2O increased ICP [median values from 14.0 (11.2–17.5) to 23.5 (19.5–26.8) mmHg, p < 0.001, respectively]. The amount of recruited lung tissue on CT was inversely correlated with the change (Δ) in ICP (rho = −0.78; p = 0.0006). Additionally, ΔCrs (rho = −0.77, p = 0.008), ΔPaCO2 (rho = 0.81, p = 0.0003), and ΔMAP (rho = −0.64, p = 0.009) were correlated with ΔICP. Baseline Crs was not predictive of ICP response to PEEP.Conclusions: The main factors associated with increased ICP after PEEP augmentation included reduced Crs, lower MAP and lung recruitment, and increased PaCO2, but none of these factors was able to predict, at baseline, ICP response to PEEP. To assess the potential benefits of increased PEEP in patients with acute brain injury, hemodynamic status, respiratory mechanics, and lung morphology should be taken into account.

Paradoxical response of intracranial pressure to shunt valve setting adjustments

BackgroundThe hydrodynamics of cerebrospinal fluid shunts have been described in vitro; however, knowledge on the response of intracranial pressure (ICP) to valve settings adjustments in vivo is limited. This study describes the effect of adjusting the shunt valve setting on ICP in a cohort of patients with complex symptom management.MethodSingle-centre retrospective observational study. Patients who underwent ICP-guided valve setting adjustments during 24-h continuous ICP monitoring, between 2014 and 2019, were included. Patients with suspected shunt malfunction were excluded. Median night ICP before and after the valve adjustments were compared (Δ night ICP). The responses of ICP to valve adjustment were divided into 3 different groups as follows: expected, paradoxical and no response. The frequency of the paradoxical response and its potential predicting factors were investigated.ResultsFifty-one patients (37 females, 14 males, mean age 38 years) receiving 94 valve setting adjustments met the study inclusion criteria. Patients’ underlying conditions were most commonly hydrocephalus (47%) or idiopathic intracranial hypertension (43%). The response of ICP to valve setting adjustments was classified as ‘expected’ in 54 cases (57%), ‘paradoxical’ in 17 cases (18%) and ‘no effect’ (Δ night ICP < 1 mmHg) in 23 cases (24%). There was a significant correlation between the Δ night ICP and the magnitude of valve setting change in both the investigated valves (Miethke ProGAV, p = 0.01 and Medtronic Strata, p = 0.02).ConclusionsParadoxical ICP changes can occur after shunt valve setting adjustments. This observation should be taken into account when performing ICP-guided valve adjustments and is highly relevant for the future development of “smart” shunt systems.