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In this randomized trial involving patients with traumatic brain injury and elevated intracranial pressure, therapeutic hypothermia plus standard care to reduce intracranial pressure did not result in outcomes better than those with standard care alone. In Europe, traumatic brain injury is the most common cause of permanent disability in people younger than 40 years of age, with the annual cost exceeding €33 billion (approximately $37.5 billion in U.S. dollars). 1 , 2 Recent statistics show a 21% increase in the incidence of traumatic brain injury during the past 5 years — three times greater than the increase in population. Despite this, management of traumatic brain injury has been underrepresented in medical research as compared with other health problems. 3 Consequently, there are few data to support the commonly used stage 2 interventions (Figure 1) for the management of . . .

Intracranial pressure (ICP) monitoring is now viewed as integral to the clinical care of many life-threatening brain insults, such as severe traumatic brain injury, subarachnoid hemorrhage, and malignant stroke. It serves to warn of expanding intracranial mass lesions, to prevent or treat herniation events as well as pressure elevation which impedes nutrient delivery to the brain. It facilitates the calculation of cerebral perfusion pressure (CPP) and the estimation of cerebrovascular autoregulatory status. Despite advancements in our knowledge emanating from a half century of experience with this technology, important controversies remain related even to fundamental aspects of ICP measurements, including indications for monitoring, ICP treatment thresholds, and management of intracranial hypertension. Here, we review the history of ICP monitoring, the underlying pathophysiology as well as current perspectives on why, when and how ICP monitoring is best used. ICP is typically assessed invasively but a number of emerging, non-invasive technologies with inherently lower risk are showing promise. In selected cases, additional neuromonitoring can be used to assist in the interpretation of ICP monitoring information and adapt directed treatment accordingly. Additional efforts to expand the evidence base relevant to ICP monitoring, related technologies and management remain a high priority in neurosurgery and neurocritical care.

Background Untimely diagnosis of intracranial hypertension may lead to delays in therapy and worsening of outcome. Transcranial Doppler (TCD) detects variations in cerebral blood flow velocity which may correlate with intracranial pressure (ICP). We investigated if intracranial hypertension can be accurately excluded through use of TCD. Method This was a multicenter prospective pilot study in patients with acute brain injury requiring invasive ICP (ICPi) monitoring. ICP estimated with TCD (ICPtcd) was compared with ICPi in three separate time frames: immediately before ICPi placement, immediately after ICPi placement, and 3 hours following ICPi positioning. Sensitivity and specificity, and concordance correlation coefficient between ICPi and ICPtcd were calculated. Receiver operating curve (ROC) and the area under the curve (AUC) analyses were estimated after measurement averaging over time. Results A total of 38 patients were enrolled, and of these 12 (31.6%) had at least one episode of intracranial hypertension. One hundred fourteen paired measurements of ICPi and ICPtcd were gathered for analysis. With dichotomized ICPi (≤20 mmHg vs >20 mmHg), the sensitivity of ICPtcd was 100%; all measurements with high ICPi (>20 mmHg) also had a high ICPtcd values. Bland-Altman plot showed an overestimation of 6.2 mmHg (95% CI 5.08–7.30 mmHg) for ICPtcd compared to ICPi. AUC was 96.0% (95% CI 89.8–100%) and the estimated best threshold was at ICPi of 24.8 mmHg corresponding to a sensitivity 100% and a specificity of 91.2%. Conclusions This study provides preliminary evidence that ICPtcd may accurately exclude intracranial hypertension in patients with acute brain injury. Future studies with adequate power are needed to confirm this result.

Background The duration of episodes of intracranial hypertension is related to poor outcome, hence the need for prompt diagnosis. Numerous issues can lead to delays in the implementation of invasive intracranial pressure (ICP) monitoring, thereby increasing the dose of intracranial hypertension to which the patient is exposed. The aim of this prospective, observational, multicenter study was to assess the magnitude of this delay, evaluating the time required for initiation of invasive ICP monitoring, from indication (T1) to initiation of the maneuver (T2) when performed by neurosurgeons compared to intensive care physicians. Methods We evaluated the impact of the operator performing the maneuver (neurosurgeon vs. intensivist) on the T2-T1 time interval, where T1 represents the time at which indication for invasive ICP monitoring is declared, and T2 the time at which the maneuver starts, defined as the skin incision. The effect of the operator performing the maneuver was evaluated through a parametric survival model. Both intraparenchymal catheters (IPCs) and external ventricular drains (EVDs) were considered as invasive ICP monitoring devices. Invasive monitoring could be performed in intensive care unit (ICU) or in operating room (OR). Results A total of 112 patients were included into the final analysis; 39 IPCs were placed by intensivists within the ICU, and a total of 73 IPCs and EVDs by neurosurgeons both within the ICU and OR settings. The mean difference in T2-T1 time for IPCs placement in the ICU was 69 min (CI 50.1–94.8) in the intensivist group and 145 min (CI 103.4–202.9) in neurosurgeon group. The mean difference between these groups, 76 min, was found to be statistically significant ( p-value  = 0.0021). In the group treated by neurosurgeons, no statistically significant differences were found in timing between the ICU and the OR. Conclusions Invasive ICP monitoring performed with IPCs in ICU begins earlier when performed by intensivists rather than neurosurgeons. This finding suggests the possibility to obtain a prompt diagnosis of intracranial hypertension when intensivists intervein directly at patient’s bedside. Further studies are needed to confirm these findings and investigate their effect on outcome.

Introduction Neuromonitoring represents a cornerstone in the comprehensive management of patients with traumatic brain injury (TBI), allowing for early detection of complications such as increased intracranial pressure (ICP) [1]. This has led to a search for noninvasive modalities that are reliable and deployable at bedside. Among these, ultrasonographic optic nerve sheath diameter (ONSD) measurement is a strong contender, estimating ICP by quantifying the distension of the optic nerve at higher ICP values. Thus, this scoping review seeks to describe the existing evidence for the use of ONSD in estimating ICP in adult TBI patients as compared to gold-standard invasive methods. Materials and Methods This review was conducted in accordance with the Joanna Briggs Institute methodology for scoping reviews, with a main search of PubMed and EMBASE. The search was limited to studies of adult patients with TBI published in any language between 2012 and 2022. Sixteen studies were included for analysis, with all studies conducted in high-income countries. Results All of the studies reviewed measured ONSD using the same probe frequency. In most studies, the marker position for ONSD measurement was initially 3 mm behind the globe, retina, or papilla. A few studies utilized additional parameters such as the ONSD/ETD (eyeball transverse diameter) ratio or ODE (optic disc elevation), which also exhibit high sensitivity and reliability. Conclusion Overall, ONSD exhibits great test accuracy and has a strong, almost linear correlation with invasive methods. Thus, ONSD should be considered one of the most effective noninvasive techniques for ICP estimation in TBI patients.

The indications for intracranial pressure (ICP) monitoring in patients with acute brain injury and the effects of ICP on patients’ outcomes are uncertain. The aims of this study were to describe current ICP monitoring practises for patients with acute brain injury at centres around the world and to assess variations in indications for ICP monitoring and interventions, and their association with long-term patient outcomes. We did a prospective, observational cohort study at 146 intensive care units (ICUs) in 42 countries. We assessed for eligibility all patients aged 18 years or older who were admitted to the ICU with either acute brain injury due to primary haemorrhagic stroke (including intracranial haemorrhage or subarachnoid haemorrhage) or traumatic brain injury. We included patients with altered levels of consciousness at ICU admission or within the first 48 h after the brain injury, as defined by the Glasgow Coma Scale (GCS) eye response score of 1 (no eye opening) and a GCS motor response score of at least 5 (not obeying commands). Patients not admitted to the ICU or with other forms of acute brain injury were excluded from the study. Between-centre differences in use of ICP monitoring were quantified by using the median odds ratio (MOR). We used the therapy intensity level (TIL) to quantify practice variations in ICP interventions. Primary endpoints were 6 month mortality and 6 month Glasgow Outcome Scale Extended (GOSE) score. A propensity score method with inverse probability of treatment weighting was used to estimate the association between use of ICP monitoring and these 6 month outcomes, independently of measured baseline covariates. This study is registered with ClinicalTrial.gov, NCT03257904. Between March 15, 2018, and April 30, 2019, 4776 patients were assessed for eligibility and 2395 patients were included in the study, including 1287 (54%) with traumatic brain injury, 587 (25%) with intracranial haemorrhage, and 521 (22%) with subarachnoid haemorrhage. The median age of patients was 55 years (IQR 39–69) and 1567 (65%) patients were male. Considerable variability was recorded in the use of ICP monitoring across centres (MOR 4·5, 95% CI 3·8–4·9 between two randomly selected centres for patients with similar covariates). 6 month mortality was lower in patients who had ICP monitoring (441/1318 [34%]) than in those who were not monitored (517/1049 [49%]; p<0·0001). ICP monitoring was associated with significantly lower 6 month mortality in patients with at least one unreactive pupil (hazard ratio [HR] 0·35, 95% CI 0·26–0·47; p<0·0001), and better neurological outcome at 6 months (odds ratio 0·38, 95% CI 0·26–0·56; p=0·0025). Median TIL was higher in patients with ICP monitoring (9 [IQR 7–12]) than in those who were not monitored (5 [3–8]; p<0·0001) and an increment of one point in TIL was associated with a reduction in mortality (HR 0·94, 95% CI 0·91–0·98; p=0·0011). The use of ICP monitoring and ICP management varies greatly across centres and countries. The use of ICP monitoring might be associated with a more intensive therapeutic approach and with lower 6-month mortality in more severe cases. Intracranial hypertension treatment guided by monitoring might be considered in severe cases due to the potential associated improvement in long-term clinical results. University of Milano-Bicocca and the European Society of Intensive Care Medicine.

Background The 'CPPopt-Guided Therapy: Assessment of Target Effectiveness' (COGiTATE) randomised controlled trial demonstrated the feasibility and safety of targeting an automated cerebral perfusion pressure (CPP) tailored to optimize cerebrovascular autoregulation (CPPopt) in patients with traumatic brain injury (TBI) requiring intracranial pressure management. The average values of the autoregulation index known as the pressure reactivity index (PRx) were not different between the intervention (CPP target = CPPopt) and control (CPP target = 60–70 mmHg) groups of the trial. This secondary analysis was performed to investigate whether: (1) in the intervention group, PRx was closer to PRxopt (PRx at CPPopt) values, indicating a more preserved reactivity, as opposed to in the control group; (2) in the intervention group, patients experienced lower hourly PRx when CPP was close to the CPPopt-based target. Methods We analyzed data from the 28 and 32 patients randomized to the control and intervention groups of the COGiTATE study, respectively. We compared hourly averaged ΔPRx (PRx minus PRxopt, where PRxopt is PRx at CPPopt) between the two groups, focusing on periods of globally preserved/homogeneous autoregulation (negative PRxopt). For each patient in the intervention group, PRx values in periods when ΔCPP (CPP minus CPPopt target) was between −5 and + 5 mm Hg were compared to values in periods when ΔCPP was outside this range. Results The median ΔPRx was significantly lower in the intervention group for negative PRxopt (Mann–Whitney U -test, p  < 0.001). For each patient in this group, the median PRx was lower in periods when CPP was close to the CPPopt-based target (Wilcoxon test, p  < 0.001). Conclusions Despite no statistically significant difference in the grand mean PRx, our results suggest that targeting CPPopt does provide a way of improving cerebrovascular reactivity in patients with TBI, offering a rational intervention for trials that address this issue. We also bring insight into aspects of the PRx/CPP relationship that should be considered for autoregulation-guided management for future clinical protocols and trials design.

Background Invasive systems are commonly used for monitoring intracranial pressure (ICP) in traumatic brain injury (TBI) and are considered the gold standard. The availability of invasive ICP monitoring is heterogeneous, and in low- and middle-income settings, these systems are not routinely employed due to high cost or limited accessibility. The aim of this consensus was to develop recommendations to guide monitoring and ICP-driven therapies in TBI using non-invasive ICP (nICP) systems. Methods A panel of 41 experts, that regularly use nICP systems for guiding TBI care, was established. Three scoping and four systematic reviews with meta-analysis were performed summarizing the current global-literature evidence. A modified Delphi method was applied for the development of recommendations. An in-person meeting with group discussions and voting was conducted. Strong recommendations were defined for an agreement of at least 85%. Weak recommendations were defined for an agreement of 75–85%. Results A total of 34 recommendations were provided (32 Strong, 2 Weak) divided into three domains: general consideration for nICP use, management of ICP using nICP methods and thresholds of nICP tools for escalating/de-escalating treatment. We developed four clinical algorithms for escalating treatment and heatmaps for de-escalating treatment. Conclusions Using a mixed-method approach involving literature review and an in-person consensus by experts, a set of recommendations designed to assist clinicians managing TBI patients using nICP systems plus clinical assessment, in the presence or absence of brain imaging, were built. Further clinical studies are required to validate the potential use of these recommendations in the daily clinical practice.

Background 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. Methods 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. Results 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 18–22 mm 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. Conclusions 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 fine balance between the secretion, composition, volume and turnover of cerebrospinal fluid (CSF) is strictly regulated. However, during certain neurological diseases, this balance can be disrupted. A significant disruption to the normal CSF circulation can be life threatening, leading to increased intracranial pressure (ICP), and is implicated in hydrocephalus, idiopathic intracranial hypertension, brain trauma, brain tumours and stroke. Yet, the exact cellular, molecular and physiological mechanisms that contribute to altered hydrodynamic pathways in these diseases are poorly defined or hotly debated. The traditional views and concepts of CSF secretion, flow and drainage have been challenged, also due to recent findings suggesting more complex mechanisms of brain fluid dynamics than previously proposed. This review evaluates and summarises current hypotheses of CSF dynamics and presents evidence for the role of impaired CSF dynamics in elevated ICP, alongside discussion of the proteins that are potentially involved in altered CSF physiology during neurological disease. Undoubtedly CSF secretion, absorption and drainage are important aspects of brain fluid homeostasis in maintaining a stable ICP. Traditionally, pharmacological interventions or CSF drainage have been used to reduce ICP elevation due to over production of CSF. However, these drugs are used only as a temporary solution due to their undesirable side effects. Emerging evidence suggests that pharmacological targeting of aquaporins, transient receptor potential vanilloid type 4 (TRPV4), and the Na + –K + –2Cl − cotransporter (NKCC1) merit further investigation as potential targets in neurological diseases involving impaired brain fluid dynamics and elevated ICP.