Baseline Intracranial Pressure Research Articles

Prospective Observational Study of Volatile Sedation with Sevoflurane After Aneurysmal Subarachnoid Hemorrhage Using the Sedaconda Anesthetic Conserving Device.

Volatile sedation is still used with caution in patients with acute brain injury because of safety concerns. We analyzed the effects of sevoflurane sedation on systemic and cerebral parameters measured by multimodal neuromonitoring in patients after aneurysmal subarachnoid hemorrhage (aSAH) with normal baseline intracranial pressure (ICP). In this prospective observational study, we analyzed a 12-h period before and after the switch from intravenous to volatile sedation with sevoflurane using the Sedaconda Anesthetic Conserving Device with a target Richmond Agitation Sedation Scale score of - 5 to - 4. ICP, cerebral perfusion pressure (CPP), brain tissue oxygenation (PBrO2), metabolic values of cerebral microdialysis, systemic cardiopulmonary parameters, and the administered drugs before and after the sedation switch were analyzed. We included 19 patients with a median age of 61years (range 46-78years), 74% of whom presented with World Federation of Neurosurgical Societies grade 4 or 5 aSAH. We observed no significant changes in the mean ICP (9.3 ± 4.2 vs. 9.7 ± 4.2mm Hg), PBrO2 (31.0 ± 13.2 vs. 32.2 ± 12.4mm Hg), cerebral lactate (5.0 ± 2.2 vs. 5.0 ± 1.9mmol/L), pyruvate (136.6 ± 55.9 vs. 134.1 ± 53.6µmol/L), and lactate/pyruvate ratio (37.4 ± 8.7 vs. 39.8 ± 9.2) after the sedation switch to sevoflurane. We found a significant decrease in mean arterial pressure (MAP) (88.6 ± 7.6 vs. 86.3 ± 5.8mm Hg) and CPP (78.8 ± 8.5 vs. 76.6 ± 6.6mm Hg) after the initiation of sevoflurane, but the decrease was still within the physiological range requiring no additional hemodynamic support. Sevoflurane appears to be a feasible alternative to intravenous sedation in patients with aSAH without intracranial hypertension, as our study did not show negative effects on ICP, cerebral oxygenation, or brain metabolism. Nevertheless, the risk of a decrease of MAP leading to a consecutive CPP decrease should be considered.

Limitations of prone positioning in patients with aneurysmal subarachnoid hemorrhage and concomitant respiratory failure

ObjectiveProne positioning (PP) is an established treatment modality for respiratory failure. After aneurysmal subarachnoid hemorrhage (aSAH), PP is rarely performed considering the risk of intracranial hypertension. The aim of this study was to analyze the effects of PP on intracranial pressure (ICP), cerebral perfusion pressure (CPP) and cerebral oxygenation following aSAH. Patients and methods: Demographic and clinical data of aSAH patients admitted over a 6-year period and treated with PP due to respiratory insufficiency were retrospectively analyzed. ICP, CPP, brain tissue oxygenation (pBrO2), respiratory parameters and ventilator settings were analyzed before and during PP. ResultsThirty patients receiving invasive multimodal neuromonitoring were included. Overall, 97 PP sessions were performed. Mean arterial oxygenation and pBrO2 increased significantly during PP. We found a significant increase in median ICP compared to the baseline level in supine position. No significant changes in CPP were observed. Five PP sessions had to be terminated early due to medically refractory ICP-crisis. The affected patients were younger (p = 0.02) with significantly higher baseline ICP values (p = 0.009). Baseline ICP correlates significantly (p < 0.001) with ICP 1 h (R: 0.57) and 4 h (R: 0.55) after onset of PP. ConclusionPP in aSAH patients with respiratory insufficiency is an effective therapeutic option improving arterial and global cerebral oxygenation without compromising CPP. The significant increase in ICP was moderate in most sessions. However, as some patients experience intolerable ICP crises during PP, continuous ICP-Monitoring is considered mandatory. Patients with elevated baseline ICP and reduced intracranial compliance should not be considered for PP.

Therapeutic Lumbar Punctures in Human Immunodeficiency Virus-Associated Cryptococcal Meningitis: Should Opening Pressure Direct Management?

BackgroundIncreased intracranial pressure (ICP) frequently complicates cryptococcal meningitis. Therapeutic lumbar punctures (LPs) have acute survival benefits in the first week, and we sought to understand the longer-term survival impact of therapeutic LPs.MethodsWe prospectively enrolled human immunodeficiency virus (HIV)–seropositive adults with cryptococcal meningitis from 2013 to 2017 in Uganda. We assessed the association between clinical characteristics, CSF parameters, and 14- and 30-day mortality by baseline ICP. We also assessed 30-day mortality by number of follow-up therapeutic LPs performed within 7 days.ResultsOur analysis included 533 participants. Participants with baseline ICP >350 mm H2O were more likely to have Glasgow Coma Scale (GCS) score <15 (P < .001), seizures (P < .01), and higher quantitative cryptococcal cultures (P < .001), whereas participants with ICP <200 mm H2O were more likely to have baseline sterile CSF cultures (P < .001) and CSF white blood cell count ≥5 cells/µL (P = .02). Thirty-day mortality was higher in participants with baseline ICP >350 mm H2O and ICP <200 mm H2O as compared with baseline ICP 200–350 mm H2O (hazard ratio, 1.55 [95% confidence interval, 1.10–2.19]; P = .02). Among survivors at least 7 days, the 30-day relative mortality was 50% higher among participants who did not receive any additional therapeutic LPs compared to those with ≥1 additional follow-up LP (33% vs 22%; P = .04), irrespective of baseline ICP.ConclusionsManagement of increased ICP remains crucial in improving clinical outcomes in cryptococcal meningitis. Guidelines should consider an approach to therapeutic LPs that is not dictated by baseline ICP.

Optic nerve ultrasound and cardiopulmonary bypass: A pilot study.

Introduction:Despite advances in surgical, anesthetic, perfusion, and postoperative care, adverse neurological consequences may occur following cardiac surgery and cardiopulmonary bypass (CPB). Consequences of the physiologic effects of CPB may alter the blood–brain barrier, autoregulation, and intracranial pressure (ICP) in the immediate postoperative period.Methods:We evaluated the effects of cardiac surgery and CPB on the central nervous system by measuring the optic nerve sheath diameter (ONSD) by using ultrasound as a surrogate marker of ICP. ONSD was measured after anesthetic induction and endotracheal intubation (time 1), after separation from CPB (time 2), and at the completion of the surgical procedure prior to leaving the OR (time 3).Results:The study cohort included 14 patients, ranging in age from newborn to 6 years. When comparing the Fontan group (n = 5) to the non-Fontan group (n = 9), four elevated ONSD observations were recorded for the Fontan patients during the study period, including one at time 1, one at time 2, and two at time 3. In Fontan versus non-Fontan patients, ONSD was greater at all three time points compared to non-Fontan. The change in the ONSD from time 1 to time 2 was greater (+0.2 mm vs. −0.1 mm), and the mean value at time 2 was significantly higher (4.2 vs. 3.5 mm, P = 0.048).Conclusions:Patients with Fontan physiology may be more prone to higher levels of baseline intracranial pressure due to elevated systemic venous pressure and decreased cardiac output. Alternatively, the chronically high central venous pressures may artificially elevate ONSD without clinical changes in ICP, necessitating the development of separate normative values based on the type of congenital heart disease.

Effects of Acute Intracranial Pressure Changes on Optic Nerve Head Morphology in Humans and Pig Model

ABSTRACT Purpose The lamina cribrosa (LC) is a layer of fenestrated connective tissue tethered to the posterior sclera across the scleral canal in the optic nerve head (ONH). It is located at the interface of intracranial and intraocular compartments and is exposed to intraocular pressure (IOP) anteriorly and intracranial pressure (ICP) or Cerebrospinal fluid (CSF) pressure (CSFP) posteriorly. We hypothesize that the pressure difference across LC will determine LC position and meridional diameter of scleral canal (also called Bruch’s membrane opening diameter; BMOD). Methods We enrolled 19 human subjects undergoing a medically necessary lumbar puncture (LP) to lower CSFP and 6 anesthetized pigs, whose ICP was increased in 5 mm Hg increments using a lumbar catheter. We imaged ONH using optical coherence tomography and measured IOP and CSFP/ICP at baseline and after each intervention. Radial tomographic ONH scans were analyzed by two independent graders using ImageJ, an open-source software. The following ONH morphological parameters were obtained: BMOD, anterior LC depth and retinal thickness. We modeled effects of acute CSFP/ICP changes on ONH morphological parameters using ANOVA (human study) and generalized linear model (pig study). Results For 19 human subjects, CSFP ranged from 5 to 42 mm Hg before LP and 2 to 19.4 mm Hg after LP. For the six pigs, baseline ICP ranged from 1.5 to 9 mm Hg and maximum stable ICP ranged from 18 to 40 mm Hg. Our models showed that acute CSFP/ICP changes had no significant effect on ONH morphological parameters in both humans and pigs. Conclusion We conclude that ONH does not show measurable morphological changes in response to acute changes of CSFP/ICP. Proposed mechanisms include compensatory and opposing changes in IOP and CSFP/ICP and nonlinear or nonmonotonic effects of IOP and CSFP/ICP across LC.

Effect of increased positive end-expiratory pressure on intracranial pressure and cerebral oxygenation: impact of respiratory mechanics and hypovolemia

BackgroundTo evaluate the impact of positive end-expiratory pressure (PEEP) on intracranial pressure (ICP) in animals with different respiratory mechanics, baseline ICP and volume status.MethodsA total of 50 male adult Bama miniature pigs were involved in four different protocols (n = 20, 12, 12, and 6, respectively). Under the monitoring of ICP, brain tissue oxygen tension and hemodynamical parameters, PEEP was applied in increments of 5 cm H2O from 5 to 25 cm H2O. Measurements were taken in pigs with normal ICP and normovolemia (Series I), or with intracranial hypertension (via inflating intracranial balloon catheter) and normovolemia (Series II), or with intracranial hypertension and hypovolemia (via exsanguination) (Series III). Pigs randomized to the control group received only hydrochloride instillation while the intervention group received additional chest wall strapping. Common carotid arterial blood flow before and after exsanguination at each PEEP level was measured in pigs with intracranial hypertension and chest wall strapping (Series IV).ResultsICP was elevated by increased PEEP in both normal ICP and intracranial hypertension conditions in animals with normal blood volume, while resulted in decreased ICP with PEEP increments in animals with hypovolemia. Increasing PEEP resulted in a decrease in brain tissue oxygen tension in both normovolemic and hypovolemic conditions. The impacts of PEEP on hemodynamical parameters, ICP and brain tissue oxygen tension became more evident with increased chest wall elastance. Compare to normovolemic condition, common carotid arterial blood flow was further lowered when PEEP was raised in the condition of hypovolemia.ConclusionsThe impacts of PEEP on ICP and cerebral oxygenation are determined by both volume status and respiratory mechanics. Potential conditions that may increase chest wall elastance should also be ruled out to avoid the deleterious effects of PEEP.

Interplay between intraocular and intracranial pressure effects on the optic nerve head in vivo

Intracranial pressure (ICP) has been proposed to play an important role in the sensitivity to intraocular pressure (IOP) and susceptibility to glaucoma. However, the in vivo effects of simultaneous, controlled, acute variations in ICP and IOP have not been directly measured. We quantified the deformations of the anterior lamina cribrosa (ALC) and scleral canal at Bruch's membrane opening (BMO) under acute elevation of IOP and/or ICP.Four eyes of three adult monkeys were imaged in vivo with OCT under four pressure conditions: IOP and ICP either at baseline or elevated. The BMO and ALC were reconstructed from manual delineations. From these, we determined canal area at the BMO (BMO area), BMO aspect ratio and planarity, and ALC median depth relative to the BMO plane. To better account for the pressure effects on the imaging, we also measured ALC visibility as a percent of the BMO area. Further, ALC depths were analyzed only in regions where the ALC was visible in all pressure conditions. Bootstrap sampling was used to obtain mean estimates and confidence intervals, which were then used to test for significant effects of IOP and ICP, independently and in interaction.Response to pressure manipulation was highly individualized between eyes, with significant changes detected in a majority of the parameters. Significant interactions between ICP and IOP occurred in all measures, except ALC visibility. On average, ICP elevation expanded BMO area by 0.17 mm2 at baseline IOP, and contracted BMO area by 0.02 mm2 at high IOP. ICP elevation decreased ALC depth by 10 μm at baseline IOP, but increased depth by 7 μm at high IOP. ALC visibility decreased as ICP increased, both at baseline (−10%) and high IOP (−17%). IOP elevation expanded BMO area by 0.04 mm2 at baseline ICP, and contracted BMO area by 0.09 mm2 at high ICP. On average, IOP elevation caused the ALC to displace 3.3 μm anteriorly at baseline ICP, and 22 μm posteriorly at high ICP. ALC visibility improved as IOP increased, both at baseline (5%) and high ICP (8%).In summary, changing IOP or ICP significantly deformed both the scleral canal and the lamina of the monkey ONH, regardless of the other pressure level. There were significant interactions between the effects of IOP and those of ICP on LC depth, BMO area, aspect ratio and planarity. On most eyes, elevating both pressures by the same amount did not cancel out the effects. Altogether our results show that ICP affects sensitivity to IOP, and thus that it can potentially also affect susceptibility to glaucoma.

Transient Increases in Intracranial Pressure After Soccer Heading

Objective To evaluate whether intracranial pressure (ICP) continued to stay elevated in trained athletes 24 hours after soccer heading. Methods Eight male subjects (21.7±1.7 years) were recruited from the UCSD soccer team to participate in the study. Baseline ICP and cardiovascular variables were recorded, and measurements were repeated after subjects underwent the heading trial. Acoustical evoked tympanic membrane displacement was used to estimate ICP, where decreasing volume displacement (-Vm) is associated with an increase in ICP. Mean arterial pressure (MAP) and heart rate (HR) were measured through the volume-clamp method. The heading trial consisted of 6 repeated headers of a soccer ball kicked from 32 meters away into a regulation goal. Follow up measurements of ICP, MAP, and HR were recorded 24 hours after heading trial. Measurements were taken in three randomized positions: 15° head-up tilt (HUT), 0° supine, -15° head-down tilt (HDT). Results At 15° HUT, baseline mean Vm was 37.81±133.21 nL, -20.82±158.27 nL immediately after heading trial (P=0.0482, paired t test), and 27.20±140.61 nL at 24 hours post soccer heading (P=0.1738, paired t test), corresponding to a significant increase in ICP immediately after the heading trial that then returns to baseline levels after 24 hours. At 0° supine, baseline mean Vm was -46.19±178.50 nL, -84.27±183.55 nL after heading trial (P=0.0321, paired t test) and -62.90±135.44 nL at 24 hours post soccer heading (P=0.5048, paired t test), corresponding to the same trend observed in the 15° HUT position. At -15° HDT, mean Vm was -148.48±196.07 nL at baseline, -187.02±186.19 nL after heading trial (P=0.1176, paired t test), and -151.10±174.86 nL at 24 hours post soccer heading (P=0.9329), corresponding to no significant increase in ICP at either time point. MAP and HR did not significantly change at any point after soccer heading. Discussions ICP significantly increased after soccer heading at 15° HUT and 0° supine but returned to baseline levels after 24 hours. ICP at -15° HDT, MAP, and HR did not significantly change immediately after soccer heading or 24 hours after soccer heading. While these results demonstrate a mild increase in ICP that subsides after 24 hours, athletes may experience these transient increases in ICP continuously for extended periods of time during their entire athletic careers. These cycles of increased ICP may result in a state of intermittent but persistently altered cerebral blood flow, which may suggest a health risk of participating in head contact sports such as soccer.

The Effects of Acute Intracranial Pressure Changes on the Episcleral Venous Pressure, Retinal Vein Diameter and Intraocular Pressure in a Pig Model

ABSTRACT Purpose Orbital veins such as the retinal veins and episcleral veins drain into the cavernous sinus, an intracranial venous structure. We studied the effects of acute intracranial pressure (ICP) elevation on episcleral venous pressure, intraocular pressure and retinal vein diameter in an established non-survival pig model. Methods In six adult female domestic pigs, we increased ICP in 5 mm Hg increments using saline infusion through a lumbar drain. We measured ICP (using parenchymal pressure monitor), intraocular pressure (using pneumatonometer), episcleral venous pressure (using venomanometer), retinal vein diameter (using OCT images) and arterial blood pressure at each stable ICP increment. The average baseline ICP was 5.4 mm Hg (range 1.5–9 mm Hg) and the maximum stable ICP ranged from 18 to 40 mm Hg. Linear mixed models with random intercepts were used to evaluate the effect of acute ICP increase on outcome variables. Results With acute ICP elevation, we found loss of retinal venous pulsation and increased episcleral venous pressure, intraocular pressure and retinal vein pressure in all animals. Specifically, acute ICP increase was significantly associated with episcleral venous pressure (β = 0.31; 95% CI 0.14–0.48, p < .001), intraocular pressure (β = 0.37, 95%CI 0.24–0.50; p < .001) and retinal vein diameter (β = 11.29, 95%CI 1.57–21.00; p = .03) after controlling for the effects of arterial blood pressure. Conclusion We believe that the ophthalmic effects of acute ICP elevation are mediated by increased intracranial venous pressure producing upstream pressure changes within the orbital and retinal veins. These results offer exciting possibilities for the development of non-invasive ophthalmic biomarkers to estimate acute ICP elevations following significant neuro-trauma.

Effects of Routine Position Changes and Tracheal Suctioning on Intracranial Pressure in Traumatic Brain Injury Patients.

Patient position change and tracheal suctioning are routine interventions in mechanically ventilated traumatic brain injury (TBI) patients. We sought to better understand the impact of these interventions on intracranial pressure (ICP) and cerebral hemodynamics. We conducted a prospective study in TBI patients requiring ICP monitoring. The timing of position changes and suctioning episodes were recorded with concurrent blood pressure and ICP measurements. We collected data on 460 patient position changes and 204 suctioning episodes over 2404 h in 18 ventilated patients (mean age 34 [13] years, median Glasgow Coma Score 4 [3-7]). We recorded 24 (20-31) positioning and 11 (6-18) suctioning episodes per patient, with 54% and 39% of position changes associated with ICP ≥22 mm Hg and cerebral perfusion pressure (CPP) <60 mm Hg, respectively, and 22% and 27% of suctioning episodes associated with an ICP ≥22 mm Hg and CPP <60 mm Hg. The median change in ICP was 11 (6-16) mm Hg after position changes and 3 (1-9) mm Hg after suctioning. Reduction in CPP to <60 mm Hg lasted ≥10 min in 17% of positioning and 11% of suctioning episodes. The baseline ICP and its amplitude were both predictive of a rise in ICP ≥22 mm Hg after positioning and suctioning episodes, whereas cerebral autoregulation was not. Baseline CPP was predictive of a decrease in CPP <60 mm Hg after both interventions. Increases in ICP and reductions in CPP are common following patient positioning and tracheal suctioning episodes. Frequently, these changes are substantial and sustained.

Intracranial-to-central venous pressure gap predicts the responsiveness of intracranial pressure to PEEP in patients with traumatic brain injury: a prospective cohort study

BackgroundMechanical ventilation (MV) with positive end-expiratory pressure (PEEP) is commonly applied in patients with severe traumatic brain injury (sTBI). However, the individual responsiveness of intracranial pressure (ICP) to PEEP varies. Thus, identifying an indicator detecting ICP responsiveness to PEEP is of great significance. As central venous pressure (CVP) could act as an intermediary to transduce pressure from PEEP to ICP, we developed a new indicator, PICGap, representing the gap between baseline ICP and baseline CVP. The aim of the current study was to explore the relationship between PICGap and ICP responsiveness to PEEP.MethodsA total of 112 patients with sTBI undergoing MV were enrolled in this prospective cohort study. ICP, CVP, cerebral perfusion pressure (CPP), static compliance of the respiratory system (Cst), and end-tidal carbon dioxide pressure (PetCO2) were recorded at the initial (3 cmH2O) and adjusted (15 cmH2O) levels of PEEP. PICGap was assessed as baseline ICP - baseline CVP (when PEEP = 3 cmH2O). The patients were classified into the ICP responder and non-responder groups based on whether ICP increment with PEEP adjusted from 3 cmH2O to 15 cmH2O was greater than 20% of baseline ICP. The above parameters were compared between the two groups, and prediction of ICP responsiveness to PEEP adjustment was evaluated by receiver operating characteristic (ROC) curve analysis.ResultsCompared with the non-responder group, the responder group had lower PICGap (1.63 ± 1.33 versus 6.56 ± 2.46 mmHg; p < 0.001), lower baseline ICP, and higher baseline CVP. ROC curve analysis suggested that PICGap was a stronger predictive indicator of ICP responsiveness to PEEP (AUC = 0.957, 95%CI 0.918–0.996; p < 0.001) compared with baseline ICP and baseline CVP, with favorable sensitivity (95.24, 95%CI 86.91–98.70%) and specificity (87.6, 95%CI 75.76–94.27%), at a cut off value of 2.5 mmHg.ConclusionThe impact of PEEP on ICP depends on the gap between baseline ICP and baseline CVP, i.e. PICGap. In addition, PICGap is a potential predictor of ICP responsiveness to PEEP adjustment in patients with sTBI.

Intracranial pressure elevation alters CSF clearance pathways

BackgroundInfusion testing is a common procedure to determine whether shunting will be beneficial in patients with normal pressure hydrocephalus. The method has a well-developed theoretical foundation and corresponding mathematical models that describe the CSF circulation from the choroid plexus to the arachnoid granulations. Here, we investigate to what extent the proposed glymphatic or paravascular pathway (or similar pathways) modifies the results of the traditional mathematical models.MethodsWe used a compartment model to estimate pressure in the subarachnoid space and the paravascular spaces. For the arachnoid granulations, the cribriform plate and the glymphatic circulation, resistances were calculated and used to estimate pressure and flow before and during an infusion test. Finally, different variations to the model were tested to evaluate the sensitivity of selected parameters.ResultsAt baseline intracranial pressure (ICP), we found a very small paravascular flow directed into the subarachnoid space, while 60% of the fluid left through the arachnoid granulations and 40% left through the cribriform plate. However, during the infusion, 80% of the fluid left through the arachnoid granulations, 20% through the cribriform plate and flow in the PVS was stagnant. Resistance through the glymphatic system was computed to be 2.73 mmHg/(mL/min), considerably lower than other fluid pathways, giving non-realistic ICP during infusion if combined with a lymphatic drainage route.ConclusionsThe relative distribution of CSF flow to different clearance pathways depends on ICP, with the arachnoid granulations as the main contributor to outflow. As such, ICP increase is an important factor that should be addressed when determining the pathways of injected substances in the subarachnoid space. Our results suggest that the glymphatic resistance is too high to allow for pressure driven flow by arterial pulsations and at the same time too small to allow for a direct drainage route from PVS to cervical lymphatics.

Intracranial Pressure After Soccer Heading

OBJECTIVETo evaluate the effect of soccer heading on intracranial pressure (ICP) in trained athletes.METHODSEight subjects (all male, 21.7±1.7 years) were recruited from the UC San Diego soccer team. ICP and cardiovascular variables were recorded before and after 6 repeats of heading a soccer ball kicked from 35 yards away, into a goal. ICP was estimated non‐invasively from acoustical evoked tympanic membrane displacement (Vm), where a more negative volume displacement is correlated with higher ICP. Mean arterial pressure (MAP), heart rate (HR; Nexfin, Netherlands), and ICP were recorded in three different postures, 15° head up tilt (HUT), 0° supine, −15° head down tilt (HDT), in a randomized order.RESULTSMean Vm at 15° HUT was 37.81±133.21 nL at baseline and −20.82±158.27 nL immediately post soccer heading (P=0.0482, paired t test), analogous to an increased ICP. At 0° supine, mean Vm was −46.19±178.50 nL at baseline and −84.27±183.55 nL after impact (P=0.0321, paired t test). At −15° HDT, mean Vm was −148.48±196.07 nL at baseline and −187.02±186.19 nL immediately post soccer heading (P=0.1176, paired t test). MAP and HR did not significantly change between the baseline and post soccer heading measurements.DISCUSSIONAfter repeated soccer ball heading, ICP significantly increased at 15° HUT and 0° supine, while ICP at −15° HDT, MAP and HR did not significantly change. The relative increase in ICP associated with HDT is comparable to previously described trends. Although the measurement technique currently employed does not provide an absolute ICP baseline, the technique has been established as useful in evaluating relative changes. Under that interpretation, these results reflect what may be an elevated ICP related to soccer heading impacts. Accordingly, the results of this study suggest a potential health risk of participation in head contact sports.Support or Funding InformationNASA (80NSSC19K0020) and Novo Nordic Foundation (NNF16OC0019196)Soccer Heading Increases Intracranial Pressure at Head Up Tilt and Supine PositionsVolume displacement of tympanic membrane (Vm), measured non‐invasively from acoustical evoked tympanic membrane displacement, indicated an increase in intracranial pressure (ICP) after soccer heading at 15° head up tilt (HUT) and 0° supine (n = 8, paired t test, *P &lt; 0.05). No significant increase in ICP at −15° head down tilt (HDT) was observed after soccer heading.Figure 1

Timing of intraventricular infusion test for diagnosing idiopathic normal pressure hydrocephalus.

Infusion tests, which measure resistance to outflow (Rout), are used in selecting patients suspected for idiopathic normal pressure hydrocephalus (iNPH) for shunt surgery. Infusion tests can be performed through an external ventricular drain (EVD). A 24-hour time gap from EVD insertion to an infusion test is a routine practice at our department due to concerns that the surgical procedure might influence the test results in the immediate postoperative period. The objective of the study was to investigate if timing of an intraventricular infusion test influences the results of the test in patients suspected for iNPH. Ten patients scheduled for an intraventricular infusion test were included. Measurements of baseline intracranial pressure (ICP) and plateau ICP were obtained during constant rate intraventricular infusion test performed at two time points (1 and 24 h after EVD insertion) and Rout was calculated from these measures and compared within patients. Eight patients completed both infusion tests. In one of the 18 infusion tests performed, it was not possible to define an ICP plateau and this infusion test was excluded, leaving 7 paired infusion tests. Median Rout was 12.9 mmHg/ml/min (range 7.0-22.0) 1 h after EVD insertion and 11.3 mmHg/ml/min (range 7.8-18.1) after 24 h. Overall, there were no statistically significant differences in Rout (P = 0.83), baseline ICP (P = 0.70), or plateau ICP (P = 0.81) between the recordings performed 1 h and 24 h after EVD insertion. For two of the seven patients with paired infusion tests, there was poor agreement between Rout values at 1 and 24 h. Overall, Rout estimates do not change significantly between 1 and 24 h after EVD insertion. We therefore propose that infusion tests can be performed shortly after surgery to reduce the period of indwelling EVD and duration of hospitalization.

Association between Cerebrovascular Reactivity Monitoring and Mortality Is Preserved When Adjusting for Baseline Admission Characteristics in Adult Traumatic Brain Injury: A CENTER-TBI Study.

Cerebral autoregulation, as measured using the pressure reactivity index (PRx), has been related to global patient outcome in adult patients with traumatic brain injury (TBI). To date, this has been documented without accounting for standard baseline admission characteristics and intracranial pressure (ICP). We evaluated this association, adjusting for baseline admission characteristics and ICP, in a multi-center, prospective cohort. We derived PRx as the correlation between ICP and mean arterial pressure in prospectively collected multi-center data from the High-Resolution Intensive Care Unit (ICU) cohort of the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study. Multi-variable logistic regression models were analyzed to assess the association between global outcome (measured as either mortality or dichotomized Glasgow Outcome Score-Extended [GOSE]) and a range of covariates (IMPACT [International Mission for Prognosis and Analysis of Clinical Trials] Core and computed tomography [CT] variables, ICP, and PRx). Performance of these models in outcome association was compared using area under the receiver operating curve (AUC) and Nagelkerke's pseudo-R2. One hundred ninety-three patients had a complete data set for analysis. The addition of percent time above threshold for PRx improved AUC and displayed statistically significant increases in Nagelkerke's pseudo-R2 over the IMPACT Core and IMPACT Core + CT models for mortality. The addition of PRx monitoring to IMPACT Core ± CT + ICP models accounted for additional variance in mortality, when compared to models with IMPACT Core ± CT + ICP alone. The addition of cerebrovascular reactivity monitoring, through PRx, provides a statistically significant increase in association with mortality at 6 months. Our data suggest that cerebrovascular reactivity monitoring may provide complementary information regarding outcomes in TBI.

Pseudo-Bayesian Model-Based Noninvasive Intracranial Pressure Estimation and Tracking.

A noninvasive intracranial pressure (ICP) estimation method is proposed that incorporates a model-based approach within a probabilistic framework to mitigate the effects of data and modeling uncertainties. A first-order model of the cerebral vasculature relates measured arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) to ICP. The model is driven by the ABP waveform and is solved for a range of mean ICP values to predict the CBFV waveform. The resulting errors between measured and predicted CBFV are transformed into likelihoods for each candidate ICP in two steps. First, a baseline ICP estimate is established over five data windows of 20 beats by combining the likelihoods with a prior distribution of the ICP to yield an a posteriori distribution whose median is taken as the baseline ICP estimate. A single-state model of cerebral autoregulatory dynamics is then employed in subsequent data windows to track changes in the baseline by combining ICP estimates obtained with a uniform prior belief and model-predicted ICP. For each data window, the estimated model parameters are also used to determine the ICP pulse pressure. On a dataset of thirteen pediatric patients with a variety of pathological conditions requiring invasive ICP monitoring, the method yielded for mean ICP estimation a bias (mean error) of 0.6mmHg and a root-mean-squared error of 3.7mmHg. These performance characteristics are well within the acceptable range for clinical decision making. The method proposed here constitutes a significant step towards robust, continuous, patient-specific noninvasive ICP determination.

Microbiological and clinical characteristics of cryptococcemia: a retrospective analysis of 85 cases in a Chinese hospital.

Cryptococcemia is a life-threatening fungal infection. Sometimes, it is hard to diagnose. The studies to describe the characteristics of cryptococcemia specifically were limited. We performed this retrospective analysis in a Chinese hospital during 2002-2015, including 85 cryptococcemia cases and 52 Cryptococcus spp. isolates. The species, mating type, antifungal susceptibility and multilocus sequence typing of Cryptococcus spp. were determined. C. neoformans var. grubii MATα of sequence type (ST) 5 is the representative strain of cryptococcemia, accounting for 51 isolates. The MIC50/90 values were 0.5/0.5, 1.0/1.0, 2.0/4.0, ≤0.06/0.25, and ≤0.06/≤0.06μg/ml for amphotericin B, flucytosine, fluconazole, itraconazole, and voriconazole, respectively. Cryptococcemia was the first diagnostic proof of cryptococcosis in 37 patients (43.5%, 37/85). Compared with the patients initially diagnosed of cryptococcosis in other sites (mainly cerebrospinal fluid), the patients firstly diagnosed by blood culture had prolonged time from admission to diagnosis of cryptococcosis (9 days vs. 2 days, P < .001) and higher 30-day mortality (54.1%vs. 20.8%, P = .003), while fewer symptoms of meningitis (45.9%vs. 100%, P < .001). For the patients receiving lumbar puncture, the occurrence of meningitis was similar between the patients firstly diagnosed by blood culture and those firstly diagnosed in other sites (94.1%vs. 100%, P = .26). However, the patients first diagnosed by blood culture had lower baseline intracranial pressure (250 mm H2O vs. 342.5 mm H2O, P = .001). In conclusion, patients with cryptococcemia as the first diagnostic proof of cryptococcosis usually had neglected subtle symptoms of meningitis, which may result in delayed diagnosis and catastrophic outcome.

Change in CSF Dynamics Responsible for ICP Elevation After Ischemic Stroke in Rats: a New Mechanism for Unexplained END?

It has been proposed that intracranial pressure (ICP) elevation and collateral failure are responsible for unexplained early neurological deterioration (END) in stroke. The study's aims were to investigate whether cerebral spinal fluid (CSF) dynamics, rather than edema, are responsible for elevation of ICP after ischemic stroke. Permanent middle cerebral artery occlusion (pMCAO) was induced with an intraluminal filament. At 24h after stroke, baseline ICP was measured and CSF dynamics were probed via a steady-state infusion method. Diffusion-weighted imaging (DWI) and T2-weighted magnetic resonance imaging were performed to define cerebral ischemic damage and the volume of brain swelling. We found that the pMCAO group exhibited a significant increase in CSF outflow resistance (2.27 ± 0.15mmHgμL-1min) compared with the sham group (0.93 ± 0.06mmHgμL-1min, p = 0.002). There was no correlation between mean ICP at 24h post-pMCAO and edema (r2 = - 0.03, p = 0.5) or infarct volumes (r2 = 0.09, p = 0.5). However, for the first time, we found a significant correlation between the baseline ICP at 24h post-stroke and the value of CSF outflow resistance. Results show that CSF outflow resistance, rather than edema, was the mechanism responsible for ICP elevation following ischemic stroke. This challenges current concepts and suggests the possibility that intracranial hypertension may be occurring undetected in a much wider range of stroke patients than is currently considered to be the case. In addition, this further supports the hypothesis that unexplained early neurological deterioration is the result of elevated ICP, leading to reduced collateral flow and cerebral perfusion.

Value of computerized shunt infusion study in assessment of pediatric hydrocephalus shunt function—a two center cross-sectional study

Hydrocephalus shunt malfunction can-also in children-occur insidiously without clear symptoms of raised intracranial pressure (ICP) or changes in ventricular size, imposing a diagnostic challenge. Computerized shunt infusion studies enable quantitative shunt function assessment. We report on feasibility and results of this technique in children in a two center cross-sectional study. Shunt infusion study (SIS) is performed with two needles inserted into a pre-chamber for ICP recording and CSF infusion. After baseline ICP recording, constant rate infusion is started until a new ICP plateau (ICPpl) is reached. Dedicated software containing the shunt's resistance characteristics calculates ICP and its amplitude outflow resistance and critical shunt pressure (CSP). Overall, 203 SIS were performed in 166 children. Shunts were defined as functional if ICPpl was <CSP and obstructed if ICPpl was > 5mmHg above CSP and borderline in between. Forty-one shunts (20.2%) were found obstructed, 26 (12.8%) had borderline characteristics, and 136 (67%) were functional. Baseline ICP in obstructed shunts was significantly above shunt operating pressure. CSF outflow resistance (Rout) and ∆ICP plateau were significantly elevated in obstructed shunts, with cut-off thresholds of 8.07mmHgmin/ml and 11.74mmHg respectively. Subgroup analysis showed smaller ventricles in 69% of revised cases. SIS is a feasible, reliable, and radiation-free technique for quantitative shunt assessment to rule out or prove shunt malfunction. Dedicated software containing shunt hydrodynamic characteristics is necessary and small children may need short-term sedation. Due to the clinical and inherent economic advantages, SIS should be more frequently used in pediatric neurosurgery.

Evidence for Mannitol as an Effective Agent Against Intracranial Hypertension: An Individual Patient Data Meta-analysis.

Mannitol is currently used to reduce intracranial pressure (ICP), but the evidence supporting its usefulness has been questioned. We aim to meta-analyze the effectiveness of mannitol in reducing ICP in adult patients with cerebral injuries and its dependency on baseline ICP values, comparing findings from individual patient data (IPD) and aggregated data (AD) meta-analysis performed on the same studies. We searched the Medline database, with no time limitation, through March 1, 2019. We selected studies for which IPD were available, with a before-after design, concerning adult patients with traumatic cerebral hemorrhages, subarachnoid hemorrhages, or hemorrhagic and ischemic stroke, treated with mannitol for increased intracranial hypertension. We extracted ICP values at baseline and at different time-points, and mannitol doses. We used a multilevel approach to account for multiple measurements on the same patient and for center variability. The AD meta-analysis and meta-regression were conducted using random-effects models. Three studies published IPD, and four authors shared their datasets. Two authors did not own their datasets anymore. Eight authors were unreachable, while 14 did not answer to our request. Overall, 7 studies provided IPD for 98 patients. The linear mixed-effects model showed that ICP decreased significantly after mannitol administration from an average baseline value of 22.1mmHg to 16.8, 12.8, and 9.7mmHg at 60, 120, and 180min after mannitol administration. ICP reduction was proportional to baseline values with a 0.64mmHg decrease for each unitary increment of the initial ICP value. Dose did not influence ICP reduction. The AD meta-analysis, based on data collected between 30 and 60min from mannitol administration not accounting for multiple time-point measurements, overestimated ICP reduction (10mmHg), while meta-regression provided similar results (0.66mmHg decrease for each unitary increase of initial ICP). Mannitol is effective in reducing pathological ICP, proportionally to the degree of intracranial hypertension. IPD meta-analysis provided a more precise quantification of ICP variation than the AD approach.