Multimodality neuromonitoring represents a crucial cornerstone for patient management after acute brain injury. Despite the potential of multimodality neuromonitoring (particularly high-resolution neuromonitoring data) to transform care, its full benefits are not yet universally realized. There remains a critical need to integrate the interpretation of complex patterns and indices into the real-time clinical decision-making processes. This requires a multidisciplinary approach, to evaluate and discuss the implications of observed patterns in a timely manner, ideally in close temporal proximity to their occurrence. Such a collaborative effort could enable clinicians to harness the full potential of multimodal data. In this educational case-based scoping review, we aim to provide clinicians, researchers, and healthcare professionals with detailed, compelling examples of potential applications of multimodality neuromonitoring, focused on high-resolution modalities within the field of traumatic brain injury. This case series showcases how neuromonitoring modalities such as intracranial pressure, brain tissue oxygenation, near-infrared spectroscopy, and transcranial Doppler can be integrated with cerebral microdialysis, neuroimaging and systemic physiology monitoring. The aim is to demonstrate the value of a multimodal approach based on high-resolution data and derived indices integrated in one monitoring tool, allowing for the improvement of diagnosis, monitoring, and treatment of patients with traumatic brain injury. For this purpose, key concepts are covered, and various cases have been described to illustrate how to make the most of this advanced monitoring technology.

The continuous monitoring of cerebral metabolic autoregulation in patients with severe traumatic brain injury (TBI) is poorly documented in the literature and largely absent from clinical practice. This study aimed to assess whether variations in intracranial pressure (ICP) and end-tidal carbon dioxide (ETCO2) can form the basis of an index for cerebrovascular autoregulation reactivity, and whether this index can improve the prediction of clinical outcomes in both adult and pediatric TBI patients.

Data from adult and pediatric patients with severe TBI were retrospectively analyzed. The Carbon Dioxide Reactivity Index (CO2Rx) was introduced as a novel tool to assess cerebrovascular reactivity in response to variations in CO2 and ICP. CO2Rx was calculated by analyzing the relationship between ICP and ETCO2, sampled at approximately 5-minute intervals, using linear correlation within moving time windows ranging from 40 to 180 min in 10-minute increments. The discriminatory power of CO2Rx in predicting clinical outcomes was evaluated through Receiver Operating Characteristic (ROC) curve analysis. The primary outcome measures included in-hospital mortality and the 12-month Glasgow Outcome Scale-Extended (GOSE) score.

The study included 218 TBI patients (40 pediatric and 178 adult). CO2Rx values showed a significant correlation with outcomes, with a CO2Rx threshold of 0.28 effectively distinguishing between favorable and unfavorable outcomes. For the fatal/non-fatal outcome, the CO2Rx crude model alone had an Area Under the Curve (AUC) of 0.737. When combined with other predictors (Impact Core + ICP + CO2Rx), this model achieved the highest AUC of 0.929.

CO2Rx demonstrated significant predictive value for mortality and unfavorable outcomes in TBI patients, serving as a continuous index of cerebrovascular reactivity to CO2. It holds potential to improve severe TBI management by optimizing the interaction between ventilation and metabolic autoregulation.

ClinicalTrials.gov Identifier: NCT NCT05043545.

Cerebral autoregulation (CA) is the mechanism that maintains stable cerebral blood flow (CBF) despite fluctuations in systemic blood pressure, crucial for brain homeostasis. Recent evidence highlights distinct regional variations in CA between the anterior (carotid) and posterior (vertebrobasilar) circulations. Non-invasive neuromonitoring techniques, such as transcranial Doppler, transfer function analysis, and near-infrared spectroscopy, facilitate the dynamic assessment of CBF and autoregulation. Studies indicate a robust autoregulatory capacity in the anterior circulation, characterized by rapid adjustments in vascular resistance. On the contrary, the posterior circulation, mainly supplied by the vertebral arteries, may have a lower autoregulatory capacity. in acute brain injuries such as intracerebral and subarachnoid hemorrhage, and traumatic brain injuries, dynamic CA can be significantly altered in the posterior circulation. Proposed physiological mechanisms of impaired CA in the posterior circulation include: (1) Decreased sympathetic innervation of the vasculature impairing compensatory vasoreactivity; (2) Endothelial dysfunction; (3) Increased cerebral metabolic rate of oxygen consumption within the visual cortex causing CBF-metabolism (i.e., neurovascular) uncoupling; and (4) Impaired blood-brain barrier integrity leading to impaired astrocytic mediated release of vasoactive substances (e.g. nitric oxide, potassium, and calcium ions). Furthermore, more research is needed on the effects of collateral circulation, as well as the circle of Willis variants, such as the fetal-type posterior cerebral artery, on dynamic CA. Improving our understanding of these mechanisms is crucial to improving the diagnosis, prognosis, and management of various cerebrovascular disorders.

Partial pressure of carbon dioxide (PaCO2) is generally known to influence outcome in patients with traumatic brain injury (TBI) at normal altitudes. Less is known about specific relationships of PaCO2 levels and clinical outcomes at high altitudes.

This is a prospective single-center cohort of consecutive patients with TBI admitted to a trauma center located at 2600 m above sea level. An unfavorable outcome was defined as a Glasgow Outcome Scale-Extended (GOSE) score < 4 at the 6-month follow-up.

We had a total of 81 patients with complete data, 80% (65/81) were men, and the median (interquartile range) age was 36 (25-50) years. Median Glasgow Coma Scale (GCS) score on admission was 9 (6-14); 49% (40/81) of patients had severe TBI (GCS 3-8), 32% (26/81) had moderate TBI (GCS 12-9), and 18% (15/81) had mild TBI (GCS 13-15). The median (interquartile range) Abbreviated Injury Score of the head (AISh) was 3 (2-4). The frequency of an unfavorable outcome (GOSE < 4) was 30% (25/81), the median GOSE was 4 (2-5), and the median 6-month mortality rate was 24% (20/81). Comparison between patients with favorable and unfavorable outcomes revealed that those with unfavorable outcome were older, (median age 49 [30-72] vs. 29 [22-41] years, P < 0.01), had lower admission GCS scores (6 [4-8] vs. 13 [8-15], P < 0.01), had higher AISh scores (4 [4-4] vs. 3 [2-4], P < 0.01), had higher Acute Physiology and Chronic Health disease Classification System II scores (17 [15-23] vs. 10 [6-14], P < 0.01), had higher Charlson scores (0 [0-2] vs. 0 [0-0], P < 0.01), and had higher PaCO2 levels (mean 35 ± 8 vs. 32 ± 6 mm Hg, P < 0.01). In a multivariate analysis, age (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.1-1.30, P < 0.01), AISh (OR 4.7, 95% CI 1.55-21.0, P < 0.05), and PaCO2 levels (OR 1.23, 95% CI 1.10-1.53, P < 0.05) were significantly associated with the unfavorable outcomes. When applying the same analysis to the subgroup on mechanical ventilation, AISh (OR 5.4, 95% CI 1.61-28.5, P = 0.017) and PaCO2 levels (OR 1.36, 95% CI 1.13-1.78, P = 0.015) remained significantly associated with the unfavorable outcome.

Higher PaCO2 levels are associated with an unfavorable outcome in ventilated patients with TBI. These results underscore the importance of PaCO2 levels in patients with TBI and whether it should be adjusted for populations living at higher altitudes.

Half of the patients with acute large artery occlusion (LAO) have poor outcomes after endovascular treatment (EVT). Early complications such as cerebral edema and symptomatic intracranial hemorrhage (sICH) can lead to early neurological deterioration (END), which correlates with hemodynamics. This study aimed to identify the hemodynamic predictors of END and outcomes in LAO patients after EVT.

A total of 76 patients with anterior circulation LAO who underwent EVT and received transcranial Doppler (TCD) monitoring were included. Bilateral middle cerebral artery (MCA) blood flow velocities (BFVs) were measured repeatedly within 1 week. Mean flow velocities (MFV) and MFV index (ipsilateral MFV/contralateral MFV) were calculated. The primary outcome was the incidence of END within 72 h. The secondary outcome was the functional outcome at 90 days-a good outcome was defined as a modified Rankin scale (mRS) score of 0-2, while a poor outcome was defined as an mRS score of 3-6.

A total of 13 patients (17.1 %) experienced END within 72 h, including 5 (38.5 %) with cerebral edema, 5 (38.5 %) with sICH, and 3 (23.0 %) with infarct progression. Multivariable logistic regression analysis showed that a higher 24 h MFV index was independently associated with END (aOR 10.5; 95 % CI 2.28-48.30, p = 0.003) and a poor 90-day outcome (aOR 5.10; 95 % CI 1.38-18.78, p = 0.014). The area under the receiver operating characteristic (ROC) curve (AUC) of the 24 h MFV index for predicting END was 0.807 (95 % CI 0.700-0.915, p = 0.0005), the sensitivity was 84.6 %, and the specificity was 66.7 %. At the 1-week TCD follow-up, patients who had poor 90-day outcomes showed significantly higher 1-week iMFV [73.5 (58.4-99.0) vs. 57.7 (45.3-76.3), p = 0.004] and MFV index [1.24 (0.98-1.57) vs.1.0 (0.87-1.15) p = 0.007]. A persistent high MFV index (PHMI) was independently associated with a poor outcome (aOR 7.77, 95 % CI 1.81-33.3, p = 0.006).

TCD monitoring within 24 h after EVT in LAO patients can help predict END, while dynamic follow-up within 1 week is valuable in predicting clinical outcomes.

partial pressure of carbon dioxide (PaCO2) is generally known to influence outcome in patients with traumatic brain injury (TBI) at normal altitudes. Less is known about specific relationships of PaCO2 levels and clinical outcomes at high altitudes.

This is a prospective single-center cohort of consecutive TBI patients admitted to a trauma center located at 2600 meter above sea level. An unfavorable outcome was defined as the Glasgow Outcome Scale-Extended (GOSE) < 4 at 6-month follow-up.

81 patients with complete data, 80% (65/81) were men, and median (IQR) age was 36 (25-50) years). Median Glasgow Coma Scale (GCS) on admission was 9 (6-14), 49% (40/81) were severe (GCS: 3-8), 32% (26/81) moderate (GCS 12 - 9), and 18% (15/81) mild (GCS 13-15) TBI. The median (IQR) Abbreviated Injury Score of the Head (AISh) was 3 (2-4). Frequency of an unfavorable outcome (GOSE < 4) was 30% (25/81), median GOSE was 4 (2-5), and 6-month mortality was 24% (20/81). Comparison between patients with favorable and unfavorable outcomes revealed that those with unfavorable outcome were older, median [49 (30-72) vs. 29 (22-41), P < 0.01], had lower admission GCS [6 (4-8) vs. 13 (8-15), P < 0.01], higher AIS head [4 (4-4) vs. 3(2-4), p < 0.01], higher APACHE II score [17(15-23) vs 10 (6-14), < 0.01), higher Charlson score [0(0-2) vs. 0 (0-0), P < 0.01] and higher PaCO2 (mmHg), mean ± SD, 39 ± 9 vs. 32 ± 6, P < 0.01. In a multivariate analysis, age (OR 1.14 95% CI 1.1-1.30, P < 0.01), AISh (OR 4.7 95% CI 1.55-21.0, P < 0.05), and PaCO2 (OR 1.23 95% CI: 1.10-1.53, P < 0.05) were significantly associated with the unfavorable outcomes. When applying the same analysis to the subgroup on mechanical ventilation, AISh (OR 5.4 95% CI: 1.61-28.5, P = 0.017) and PaCO2 (OR 1.36 95% CI: 1.13-1.78, P = 0.015) remained significantly associated with the unfavorable outcome.

Higher PaCO2 levels are associated with an unfavorable outcome in ventilated TBI patients. These results underscore the importance of PaCO2 level in TBI patients and whether it should be adjusted for populations living at higher altitudes.

Methods evaluating the status of the injured brain have evolved over the past 63 years since Lundberg first reported clinical measurement of intracranial pressure (ICP) to evaluate the status of the injured brain (Lundberg, Acta Psychiatr Scand Suppl. 36:1-193, 1960). Subsequent evaluation involved measurement of the autoregulatory capacity of the brain by measuring cerebral blood flow (CBF) with decreasing mean arterial pressure (MAP) to define the critical CPP where the vasodilatory capacity of the cerebral circulation is exceeded and CBF begins to fall (CPP of 50 mmHg). A seminal advance was made by Marmarou (Marmarou et al., J Neurosurg. 48:332-344, 1978) who measured brain compliance by injecting a bolus of saline into the intracranial catheter while measuring the rise in intracranial pressure (ICP) otherwise known as induced pressure reactivity (iPRx). Seeking to utilise continuous measurement of iPRx in traumatic brain injury (TBI) patients with continuous monitoring of ICP, the ICP response to arterial pulsations was developed to evaluate the optimal CPP patients with raised ICP by the arterial pulsations-based iPRx. A similar approach was made with Doppler measurement of CBF with arterial pulsations for iCVRx to guide optimal CPP (CPPopt). Both iPRx and iCVRx are associated with microvascular shunts (MVS) and can accurately measure the critical CPP, whereas the CBF autoregulation curve by decreasing MAP does not. Sophisticated continuous multimodal monitoring established with ICM+ algorithms successfully identifies CPPopt for ICP control and identifies CBF dysregulation as related to outcome, but does not provide insights into the mechanisms involved in the loss of CBF autoregulation as related to increased ICP and potentially effective treatments (Froese et al., Neurocrit Care. 34:325-335, 2021).

The neurovascular system forms the interface between the tissue of the central nervous system (CNS) and circulating blood. It plays a critical role in regulating movement of ions, small molecules, and cellular regulators into and out of brain tissue and in sustaining brain health. The neurovascular unit (NVU), the cells that form the structural and functional link between cells of the brain and the vasculature, maintains the blood-brain interface (BBI), controls cerebral blood flow, and surveils for injury. The neurovascular system is dynamic; it undergoes tight regulation of biochemical and cellular interactions to balance and support brain function. Development of an intrinsic circadian clock enables the NVU to anticipate rhythmic changes in brain activity and body physiology that occur over the day-night cycle. The development of circadian neurovascular function involves multiple cell types. We address the functional aspects of the circadian clock in the components of the NVU and their effects in regulating neurovascular physiology, including BBI permeability, cerebral blood flow, and inflammation. Disrupting the circadian clock impairs a number of physiological processes associated with the NVU, many of which are correlated with an increased risk of dysfunction and disease. Consequently, understanding the cell biology and physiology of the NVU is critical to diminishing consequences of impaired neurovascular function, including cerebral bleeding and neurodegeneration.

The cerebral oxygen cascade includes three key stages: (a) convective oxygen delivery representing the bulk flow of oxygen to the cerebral vascular bed; (b) diffusion of oxygen from the blood into brain tissue; and (c) cellular utilisation of oxygen for aerobic metabolism. All three stages may become dysfunctional after resuscitation from cardiac arrest and contribute to hypoxic-ischaemic brain injury (HIBI). Improving convective cerebral oxygen delivery by optimising cerebral blood flow has been widely investigated as a strategy to mitigate HIBI. However, clinical trials aimed at optimising convective oxygen delivery have yielded neutral results. Advances in the understanding of HIBI pathophysiology suggest that impairments in the stages of the oxygen cascade pertaining to oxygen diffusion and cellular utilisation of oxygen should also be considered in identifying therapeutic strategies for the clinical management of HIBI patients. Culprit mechanisms for these impairments may include a widening of the diffusion barrier due to peri-vascular oedema and mitochondrial dysfunction. An integrated approach encompassing both intra-parenchymal and non-invasive neuromonitoring techniques may aid in detecting pathophysiologic changes in the oxygen cascade and enable patient-specific management aimed at reducing the severity of HIBI.

Intrahospital transport (IHT) of Neurosurgical Intensive Care Unit (NICU) patients for cranial computed tomography (CCT) scans is associated with a high rate of complications. The potential of serum biomarkers to estimate the risk for complications associated with IHT and improve their safety remains underexplored. The present study investigated the influence of several serum biomarkers on IHT-associated complications in brain-injured NICU patients.

A total of 523 IHTs in 223 NICU patients were prospectively analyzed (05/2019-05/2020). Hemoglobin, hematocrit, serum sodium, and albumin levels were evaluated as serum biomarkers. Each patient's demographic data, CCT scan, NICU parameters and modified Rankin Scale at discharge as well as indications, consequences, and complications of IHTs were analyzed.

In 58.7% of all IHTs, at least one IHT-associated complication was observed with 60.1% of all IHTs having no therapeutic consequence. Significantly lower rates of increased intracranial pressure (ICP; P<0.0001), decreased cerebral perfusion pressure (CPP; P=0.03) as well as hemodynamic (P<0.0001) and pulmonary events (P=0.01) were observed in patients with higher hemoglobin levels prior to IHT. Additionally, higher hematocrit levels before IHT were associated with a fewer rate of hemodynamic (P<0.0001), pulmonary (P=0.006), ICP (P<0.0001), and CPP (P=0.01) events.

Higher levels of hemoglobin and hematocrit are associated with less complications with respect to ICP, CPP, hemodynamic and pulmonary events during IHT in NICU patients. Therefore, these biomarkers may be helpful for risk assessment of potential complications prior to IHT.

Adrenoceptor and calcium channel modulating medications are widely used in clinical practice for acute neurological and systemic conditions. It is generally assumed that the cerebrovascular effects of these drugs mirror that of their systemic effects - and this is reflected in how these medications are currently used in clinical practice. However, recent research suggests that there are distinct cerebrovascular-specific effects of these medications that are related to the unique characteristics of the cerebrovascular anatomy including the regional heterogeneity in density and distribution of adrenoceptor subtypes and calcium channels along the cerebrovasculature. In this review, we critically evaluate existing basic science and clinical research to discuss known and putative interactions between adrenoceptor and calcium channel modulating pharmacotherapies, the neurovascular unit, and cerebrovascular anatomy. In doing so, we provide a rationale for selecting vasoactive medications based on lesion location and lay a foundation for future investigations that will define neuroprotective paradigms of adrenoceptor and calcium channel modulating therapies to improve neurological outcomes in acute neurological and systemic disorders.

In traumatic brain injury (TBI) the patterns of intracranial pressure (ICP) waveforms may reflect pathological processes that ultimately lead to unfavorable outcome. In particular, ICP slow waves (sw) (0.005-0.05 Hz) magnitude and complexity have been shown to have positive association with favorable outcome. Mild-moderate hypocapnia is currently used for short periods to treat critical elevations in ICP. Our goals were to assess changes in the ICP sw activity occurring following sudden onset of mild-moderate hypocapnia and to examine the relationship between changes in ICP sw activity and other physiological variables during the hypocapnic challenge.

ICP, arterial blood pressure (ABP), and bilateral middle cerebral artery blood flow velocity (FV), were prospectively collected in 29 adult severe TBI patients requiring ICP monitoring and mechanical ventilation in whom a minute volume ventilation increase (15-20% increase in respiratory minute volume) was performed as part of a clinical CO₂-reactivity test. The time series were first treated using FFT filter (pass-band set to 0.005-0.05 Hz). Power spectral density analysis was performed. We calculated the following: mean value, standard deviation, variance and coefficient of variation in the time domain; total power and frequency centroid in the frequency domain; cerebrospinal compliance (Ci) and compensatory reserve index (RAP).

Hypocapnia led to a decrease in power and increase in frequency centroid and entropy of slow waves in ICP and FV (not ABP). In a multiple linear regression model, RAP at the baseline was the strongest predictor for the decrease in the power of ICP slow waves (p < 0.001).

In severe TBI patients, a sudden mild-moderate hypocapnia induces a decrease in mean ICP and FV, but also in slow waves power of both signals. At the same time, it increases their higher frequency content and their morphological complexity. The difference in power of the ICP slow waves between the baseline and the hypocapnia period depends on the baseline cerebrospinal compensatory reserve as measured by RAP.

Intrahospital transports (IHTs) of neurosurgical intensive care unit (NICU) patients can be hazardous. Increasing intracranial pressure (ICP) and/or decreasing cerebral perfusion pressure (CPP) as well as cardiopulmonary alterations are common complications of an IHTs, which can lead to secondary brain injury. This study was performed to assess several serum biomarkers concerning their potential to improve safety of IHTs in mechanically ventilated NICU patients.

All IHTs of mechanically ventilated and sedated NICU patients from 03/2017 to 01/2018 were retrospectively analyzed. Intracranial pressure and CPP measurements were performed in all patients. Serum hemoglobin, hematocrit, and serum sodium were defined as serum biomarkers. Demographic data, computed tomography scan on admission, Simplified Acute Physiology Score and Acute Physiology and Chronic Health Evaluation II, modified Rankin Scale, indication and consequence of IHTs were analyzed. Alteration of ICP/CPP, hemodynamic and pulmonary events were defined as complications. The study population was stratified into patients with the occurrence of a complication and absence of a complication.

We analyzed a total number of 184 IHTs in 70 NICU patients with an overall complication rate of 57.6%. Of all, 32.1% IHTs had no direct therapeutic consequence. In patients with higher hemoglobin values prior to IHT less complications occurred, concerning ICP (P = .001), CPP (P = .001), hemodynamic (P = .005), and pulmonary (P < .0001) events. In addition, complications concerning ICP (P = .001), CPP (P = .001), hemodynamic (P = .005), and pulmonary problems (P = .002) were significantly lower in patients with higher hematocrit values before IHT.

Intrahospital transports of mechanically ventilated NICU patients carry a high risk of increased ICP and hemodynamic complications and should be performed restrictively. Higher values of hemoglobin and hematocrit prior to IHT were associated with less complications with regard to ICP, CPP as well as hemodynamic and pulmonary events and could be helpful to assess the potential risk of complications prior to IHTs.

Secondary insults worsen outcomes after traumatic brain injury (TBI). However, data on intraoperative secondary insults are sparse. The primary aim of this study was to examine the prevalence of intraoperative secondary insults during orthopedic surgery after moderate-severe TBI. We also examined the impact of intraoperative secondary insults on postoperative head computed tomographic scan, intracranial pressure (ICP), and escalation of care within 24 hours of surgery.

We reviewed medical records of TBI patients 18 years and above with Glasgow Coma Scale score <13 who underwent single orthopedic surgery within 2 weeks of TBI. Secondary insults examined were: systemic hypotension (systolic blood pressure<90 mm Hg), intracranial hypertension (ICP>20 mm Hg), cerebral hypotension (cerebral perfusion pressure<50 mm Hg), hypercarbia (end-tidal CO2>40 mm Hg), hypocarbia (end-tidal CO2<30 mm Hg in absence of intracranial hypertension), hyperglycemia (glucose>200 mg/dL), hypoglycemia (glucose<60 mg/dL), and hyperthermia (temperature >38°C).

A total of 78 patients (41 [18 to 81] y, 68% male) met the inclusion criteria. The most common intraoperative secondary insults were systemic hypotension (60%), intracranial hypertension and cerebral hypotension (50% and 45%, respectively, in patients with ICP monitoring), hypercarbia (32%), and hypocarbia (29%). Intraoperative secondary insults were associated with worsening of head computed tomography, postoperative decrease of Glasgow Coma Scale score by ≥2, and escalation of care. After Bonferroni correction, association between cerebral hypotension and postoperative escalation of care remained significant (P<0.001).

Intraoperative secondary insults were common during orthopedic surgery in patients with TBI and were associated with postoperative escalation of care. Strategies to minimize intraoperative secondary insults are needed.

Discrepant data exist regarding the incidence and severity of clinical problems related to intra-hospital transport of brain-injured patients and no consensus exists whether modern-day intra-hospital transport represents a safe or potentially problematic environment for neurointensive care unit (NICU) patients.

We examined the incidence of clinical complications and physiological derangements that occurred in 160 neurologically injured patients (90 males, 70 females, mean age 57 ± 17 years) who underwent intra-hospital transport (288 cases, 237 scheduled, 51 unscheduled) for computed tomography scans.

Our findings indicate that (1) at least one significant complication (predominantly hemodynamic) occurred in over one-third (36%) of all transports (p = n.s scheduled vs. unscheduled) necessitating the deployment of interventions designed to treat changes in arterial pressure (2) despite the presence of trained medical personnel and availability of specialized equipment, intra-cranial pressure was not adequately monitored during transports (especially in patients with intra-cranial hypertension prior to transport) (3) intra-hospital transfer was associated with minor but statistically significant clinical changes, including a reduction in arterial partial pressure of oxygen (Pa(O(2)))/inspired oxygen fraction (Fi(O(2))) (only in the scheduled transport population), decreased arterial lactate levels (scheduled transport population), lowered body temperature (scheduled transport population), and increased arterial partial pressure of carbon dioxide (Pa(CO(2))) (scheduled transport population).

Intra-hospital transport of brain-injured NICU patients may present some hazards even if performed by skilled personnel with specialized equipment. In Trauma Centers such as ours, an improvement in the frequency of neuromonitoring [intra-cranial pressure (ICP) and end-tidal CO2 (ET(CO(2)))] during transport is recommended.

Intracranial pressure (ICP) remains a pivotal physiological signal for managing brain injury and subarachnoid hemorrhage (SAH) patients in neurocritical care units. Given the vascular origin of the ICP, changes in ICP waveform morphology could be used to infer cerebrovascular changes. Clinical validation of this association in the setting of brain trauma, and SAH is challenging due to the multi-factorial influences on, and uncertainty of, the state of the cerebral vasculature.

To gain a more controlled setting, in this articel, we study ICP signals recorded in four uninjured patients undergoing a CO2 inhalation challenge in which hypercapnia induced acute cerebral vasodilatation. We apply our morphological clustering and analysis of intracranial pressure (MOCAIP) algorithm to identify six landmarks on individual ICP pulses (based on the three established ICP sub-peaks; P1, P2, and P3) and extract 128 ICP morphological metrics. Then by comparing baseline, test, and post-test data, we assess the consistency and rate of change for each individual metric.

Acute vasodilatation causes consistent changes in a total of 72 ICP pulse morphological metrics and the P2 sub-region responds to cerebral vascular changes in the most consistent way with the greatest change as compared to P1 and P3 sub-regions.

Since the dilation/constriction of the cerebral vasculature resulted in detectable consistent changes in ICP MOCIAP metrics, by an extended monitoring practice of ICP that includes characterizing ICP pulse morphology, one can potentially detect cerebrovascular changes, continuously, for patients under neurocritical care.

Hyperventilation has been an integral, but poorly validated part of neuroanesthetic practice. We conducted a two-period, crossover, randomized trial to evaluate surgeon-assessed brain bulk and measured intracranial pressure (ICP) in patients undergoing craniotomy for removal of supratentorial brain tumors during moderate hypocapnia or normocapnia.

Two-hundred and seventy-five adult patients with supratentorial brain tumors were randomized to one of two treatment sequences: hyperventilation (arterial carbon dioxide tension, PaCO2 = 25 +/- 2 mm Hg) followed by normoventilation (PaCO2 = 37 +/- 2 mm Hg) or normoventilation followed by hyperventilation. Ventilation and end-tidal CO2 tension were kept constant for 20 min. Patients were also randomly assigned to receive a propofol infusion or isoflurane anesthesia. At the end of each study period, subdural ICP was measured and the neurosurgeon, blinded to the treatment group, was asked to rate the brain bulk using a four-point scale.

Using a generalized estimation equation model, we found that hyperventilation decreased the risk of increased brain bulk by 45%, P = 0.004, 95% confidence intervals 22% to 61%, and the number needed to treat was 8. The mean (+/-SD) ICP during hyperventilation, 12.3 +/- 8.1 mm Hg, was lower than that during normoventilation, 16.2 +/- 9.6 mm Hg, P < 0.001. Anesthetic regimen did not affect brain bulk assessment or ICP.

In patients with supratentorial brain tumors, intraoperative hyperventilation improves surgeon-assessed brain bulk which was associated with a decrease in ICP.

Multimodality monitoring of cerebral physiology encompasses the application of different monitoring techniques and integration of several measured physiologic and biochemical variables into assessment of brain metabolism, structure, perfusion, and oxygenation status. Novel monitoring techniques include transcranial Doppler ultrasonography, neuroimaging, intracranial pressure, cerebral perfusion, and cerebral blood flow monitors, brain tissue oxygen tension monitoring, microdialysis, evoked potentials, and continuous electroencephalogram. Multimodality monitoring enables immediate detection and prevention of acute neurologic injury as well as appropriate intervention based on patients' individual disease states in the neurocritical care unit. Real-time analysis of cerebral physiologic, metabolic, and cardiovascular parameters simultaneously has broadened knowledge about complex brain pathophysiology and cerebral hemodynamics. Integration of this information allows for more precise diagnosis and optimization of management of patients with brain injury.

Maintaining intracranial pressure (ICP) below 20-25 mmHg is an important clinical goal in the treatment of patients with traumatic brain injury (TBI). It is well known that the partial pressure of arterial CO2 (PaCO2) can affect cerebral blood flow, cerebral blood volume, and therefore ICP. The end-tidal CO2 (ETCO2) is usually monitored by clinicians as a proxy for PaCO2. We show examples where subclinical fluctuations in ETCO2 are associated with clinically significant fluctuations in ICR. We estimated ICP from past and present values of ETCO2 with a linear estimator. The variance of the ICP residuals was 37 percent of the variance of the ICP signal at frequencies above 0.33 mHz. We suggest that a large proportion of clinically significant ICP fluctuations could be eliminated or reduced if the patients ventilation and CO2 levels were more tightly regulated.

The aim of this review was to consider the effects of induced hypocapnia both on systemic physiology and on the physiology of the intracranial system. Hyperventilation lowers intracranial pressure (ICP) by the induction of cerebral vasoconstriction with a subsequent decrease in cerebral blood volume. The downside of hyperventilation, however, is that cerebral vasoconstriction may decrease cerebral blood flow to ischemic levels. Considering the risk-benefit relation, it would appear to be clear that hyperventilation should only be considered in patients with raised ICP, in a tailored way and under specific monitoring. Controversy exists, for instance, on specific indications, timing, depth of hypocapnia, and duration. This review has specific reference to traumatic brain injury, and is based on an extensive evaluation of the literature and on expert opinion.

Trauma to the central nervous system can have devastating consequences for both the person who sustained the injury and his/her family/loved ones. This article first discusses pathophysiology in relation to altered cerebral haemodynamics and changes that occur after spinal injury. Following on from the underpinning theoretical perspectives, the article reviews the nursing care and management strategies required by patients who have sustained either a traumatic head injury or acute spinal injury, with the aim of controlling secondary injury, which is preventable. This ensures the patient will have the best possible prognosis and outcome.

To review the scientific basis for and utility of the traditional cerebral monitors used currently in neurointensive care, together with research techniques that are soon likely to become used in managing severe head injury and subarachnoid haemorrhage.

Firstly, the pathophysiology of acute brain injury including cerebral haemodynamics, oxygen and metabolism and the role of secondary insults are discussed. Secondly, the importance of assessment of cerebrovascular autoregulation and reactivity is reviewed together with methods for its continuous non-invasive measurement using transcranial Doppler and intracranial pressure/arterial pressure recordings. Thirdly, the respective roles of jugular venous oxygen and brain tissue oxygen monitoring are analysed. Fourthly, the use of cerebral microdialysis is described, together with an overview of its utility.

Cerebral multimodal monitoring can be helpful for the optimal management of acute brain injury and essential for future exploratory trials of neuroprotective drugs.

The brain is sensitive to changes in substrate delivery. In neurologically critically ill patients (e.g., those with head injury, subarachnoid hemorrhage, or stroke), interruption of this supply causes ischemic brain damage and thus impairs the outcome. To prevent, detect, and treat these ischemic events as soon as possible, the cerebral blood flow is continuously monitored, its coupling or not with the consumption of oxygen and so forth, and the detected derangements of normal physiology. Intracranial pressure and cerebral perfusion pressure are two parameters that often reflect ischemic events, and thus it is mandatory to continuously measure them. To better assess cerebral hemodynamics, jugular bulb oxymetry and brain pressure tissue oxygen monitoring are two neuromonitoring techniques that allow for a better understanding of the balance between oxygen supply and consumption, and therefore are useful in directing therapy. Transcranial Doppler ultrasonography is a noninvasive technique with the same purpose but with less clinical relevance. The new neuromonitoring technique, microdialysis, is useful for understanding the mechanisms involved in brain ischemia. However, it is clear that the physician who interprets the measurements given by devices and the clinical data (e.g., temperature, glycemia) is still the cornerstone in the management of neurologically critically ill patients.

We used steady-state susceptibility contrast MRI to evaluate the regional cerebral blood volume (rCBV) response to hypocapnia in anesthetised rats. The rCBV was determined in the dorsoparietal neocortex, the corpus striatum, the cerebellum, as well as blood volume in extracerebral tissue (group 1). In addition, we used laser-Doppler flow (LDF) measurements in the left dorsoparietal neocortex (group 2), to correlate changes in CBV and in cerebral blood flow. Baseline values, expressed as a percentage of blood volume in each voxel, were higher in the brain regions than in extracerebral tissue. Hypocapnia (P(a)CO(2) approximately 25 mmHg) resulted in a significant decrease in CBV in the cerebellum (-17 +/- 9%), in the corpus striatum (-15 +/- 6%) and in the neocortex (-12 +/- 7%), compared to the normocapnic CBV values (group 1). These changes were in good agreement with the values obtained using alternative techniques. No significant changes in blood volume were found in extracerebral tissue. The CBV changes were reversed during the recovery period. In the left dorsoparietal neocortex, the reduction in LDF (group 2) induced by hypocapnia (-21 +/- 8%) was in accordance with the values predicted by the Poiseuille's law. We conclude that rCBV changes during CO(2) manipulation can be accurately measured by susceptibility contrast MRI. Abbreviations used: ANOVA analysis of variance CBF cerebral blood flow CBV cerebral blood volume CPMG Carr-Purcell-Meiboom-Gill FiO(2) fractional inspired oxygen ICP intracranial pressure LDF laser-Doppler flow MABP mean arterial blood pressure MRI magnetic resonance imaging MTT mean transit time PaCO(2) arterial partial pressure of carbon dioxide PaO(2) arterial partial pressure of oxygen PET positron emission tomography rCBV regional cerebral blood volume SPECT single-photon emission computed tomography

The pathogenesis of traumatic brain swelling remains unclear. The generally held view is that brain swelling is caused primarily by vascular engorgement and that edema plays a relatively minor role in the swelling process. The goal of this study was to examine the roles of cerebral blood volume (CBV) and edema in traumatic brain swelling.

Both brain-tissue water and CBV were measured in 76 head-injured patients, and the relative contribution of edema and blood to total brain swelling was determined. Comparable measures of brain-tissue water were obtained in 30 healthy volunteers and CBV in seven volunteers. Brain edema was measured using magnetic resonance imaging, implementing a new technique for accurate measurement of total tissue water. Measurements of CBV in a subgroup of 31 head-injured patients were based on consecutive measures of cerebral blood flow (CBF) obtained using stable xenon and calculation of mean transit time by dynamic computerized tomography scanning after a rapid bolus injection of iodinated contrast material. The mean (+/- standard deviation) percentage of swelling due to water was 9.37+/-8.7%, whereas that due to blood was -0.8+/-1.32%.

The results of this study showed that brain edema is the major fluid component contributing to traumatic brain swelling. Moreover, CBV is reduced in proportion to CBF reduction following severe brain injury.

We have analyzed and evaluated what is the best metabolic monitoring system to determine the prognosis for maintenance of neurological function in severe head injured patients. Acute subdural hematoma (ASDH) was recognized in fifteen of 22 patients and cerebral contusion in seven in this series. Intracranial pressure (ICP), jugular venous pH and jugular bulb venous oxygen saturation (SjO2) were continuously monitored as soon as possible following stabilization. The measurement of cerebral blood flow (CBF) was carried out using a stable Xenon-computerized tomography (Xe-CT). After measuring CBF, 3% carbon dioxide (CO2) loading was conducted to determine CO2 responses (delta CBF/delta CO2). In patients who died (D), jugular venous pH showed evidence of acidosis (6.3-7.2) with delta CBF/delta CO2 < 1 and cerebral metabolic rate of oxygen (CMRO2) < 1.21 within several hours of the trauma. On the other hand, arterial pH was shown to be within the normal range. In vegetative state (VS) and severe disability (SD) patients, jugular venous pH was shown to be within normal range, with delta CBF/delta CO2 < 1 and 1.44 < CMRO2 < 1.79. In all of moderate disability (MD) and good recovery (GR) patients, jugular venous pH was shown to be within the normal range, with delta CBF/delta CO2 > 1 and 1.65 < CMRO2 < 1.85. These results suggest that jugular venous pH, CO2 response and CMRO2, were useful as early prognostic indicators in the maintenance of neurological function.

Intracranial pressure depends on cerebral tissue volume, cerebrospinal fluid volume (CSFV) and cerebral blood volume (CBV). Physiologically, their sum is constant (Monro-Kelly equation) and ICP remains stable. When the blood brain barrier (BBB) is intact, the volume of cerebral tissue depends on the osmotic pressure gradient. When it is injured, water movements across the BBB depend on the hydrostatic pressure gradient. CBV depends essentially on cerebral blood flow (CBF), which is strongly regulated by cerebral vascular resistances. In experimental studies, a decrease in oncotic pressure does not increase cerebral oedema and intracranial hypertension (ICHT). On the other hand, plasma hypoosmolarity increases cerebral water content and therefore ICP, if the BBB is intact. If it is injured, neither hypoosmolarity nor hypooncotic pressure modify cerebral oedema. Therefore, all hypotonic solutes may aggravate cerebral oedema and are contra-indicated in case of ICHT. On the other hand, hypooncotic solutes do not modify ICP. The osmotic therapy is one of the most important therapeutic tools for acute ICHT. Mannitol remains the treatment of choice. It acts very quickly. An i.v. perfusion of 0.25 g.kg-1 is administered over 20 minutes when ICP increases. Hypertonic saline solutes act in the same way, however they are not more efficient than mannitol. CO2 is the strongest modulating factor of CBF. Hypocapnia, by inducing cerebral vasoconstriction, decreases CBF and CBV. Hyperventilation is an efficient and rapid means for decreasing ICP. However, it cannot be used systematically without an adapted monitoring, as hypocapnia may aggravate cerebral ischaemia. Hyperthermia is an aggravating factor for ICHT, whereas moderate hypothermia seems to be beneficial both for ICP and cerebral metabolism. Hyperglycaemia has no direct effect on cerebral volume, but it may aggravate ICHT by inducing cerebral lactic acidosis and cytotoxic oedemia. Therefore, infusion of glucose solutes is contra-indicated in the first 24 hours following head trauma and blood glucose concentration must be closely monitored and controlled during ICHT episodes.

The mathematical model presented in a previous work is used to simulate the time pattern of intracranial pressure (ICP) and of blood velocity in the middle cerebral artery (VMCA) in response to maneuvers simultaneously affecting mean systemic arterial pressure (SAP) and end-tidal CO2 pressure. In the first stage of this study, a sensitivity analysis was performed to clarify the role of some important model parameters [cerebrospinal fluid (CSF) outflow resistance, intracranial elastance coefficient, autoregulation gain, and the position of the regulation curve] during CO2 alteration maneuvers performed at different SAP levels. The results suggest that the dynamic "ICP-VMCA" relationship obtained during changes in CO2 pressure may contain important information on the main factors affecting intracranial dynamics. In the second stage, the model was applied to the reproduction of real ICP and velocity tracings in neurosurgical patients. Ten distinct tracings, taken from six patients during CO2 changes at different mean SAP levels, were reproduced. Best fitting between model and clinical curves was achieved by minimizing a least-squares criterion function and adjusting certain parameters that characterize CSF circulation, intracranial compliance, and the strength of the regulation mechanisms. A satisfactory reproduction was achieved in all cases, with parameter numerical values in the ranges reported in clinical literature. It is concluded that the model may be used to give reliable estimations of the main factors affecting intracranial dynamics in individual patients, starting from routine measurements performed in neurosurgical intensive care units.

To study the cerebrovascular reactivity to CO2 after severe head injury to establish the clinical and prognostic relevance of CO2 reactivity.

Cerebrovascular reactivity to CO2 was studied in 20 patients with severe head injuries at 3.0+/-1.8 days after trauma onset. Two cerebral blood flow studies were performed to measure CO2 reactivity: the first study in a condition of normocapnia and the second study in a condition of relative hypocapnia.

Global reactivity was superimposable to that found in awake, normocapnic subjects and did not correlate with age and Glasgow Coma Scale score but was dependent on the type of brain lesion. Moreover, reactivity correlated with outcome in patients studied after the first 3 days after trauma.

Our data suggest that cerebrovascular reactivity is (a) almost preserved after a severe head injury; (b) significantly influenced by type of brain lesion; (c) prognostically relevant only in patients studied after the first 3 days after trauma.

CO2 reactivity was tested in patients with transcranial Doppler sonography (TCD) and endtidal CO2 measurements after an average time interval of ten months after subarachnoid haemorrhage (SAH). After deliberately changing breathing there was a significant change in endtidal CO2 and in flow velocities in all three examination groups. Comparing 27 patients with SAH and 5 patients treated for incidental aneurysms and 20 patients without cerebrovascular disease there were no significant differences in CO2 reactivity. Furthermore, there were no right to left differences. In 12 patients with vasospasm, two of them treated by percutaneous transluminal angioplasty for delayed ischaemic deficits, CO2 reactivity was normal at the time of investigation. Furthermore, normal CO2 reactivity was found in patients after SAH and surgery for ruptured aneurysms regardless of the severity of the SAH.

Brain edema and vascular engorgement have been used interchangeably to describe brain swelling associated with severe brain trauma and their relative contribution of these compartments to the swelling process remains controversial. In this report, imaging techniques for measurement of brain water and blood volume have been used to study the relative contribution of blood volume and tissue water to the swelling process in severely brain injured patients. More specifically, magnetic resonance techniques for non-invasive tissue water measures founded on mathematical models and later substantiated in laboratory and clinical studies were used for measure of brain tissue water. These studies were combined with measures of cerebral blood volume utilizing indicator dilution methods. Studies indicated that brain water was increased while blood volume decreased. These studies provide compelling evidence that the major contributor to brain swelling is brain edema and not blood volume. Therapies should now be targeted toward preventing edema development and enhancing edema resolution.

Knowledge of cerebral blood volume (CBV) is invaluable in identifying the primary cause of brain swelling in patients with stroke or severe head injury, and it might also help in clinical decision making in patients thought to have hemodynamic transient ischemic attacks (TIAs). This investigation is concerned with the development and clinical application of a new method for quantitative regional CBV measurements.

The technique is based on consecutive measurements of cerebral blood flow (CBF) by xenon/CT and tissue mean transit time (MTT) by dynamic CT after a rapid iodinated contrast bolus injection. CBV maps are produced by multiplication of the CBF and MTT maps in accordance with the Central Volume Principle: CBV = CBF x MTT. The method is rapid and easily implemented on CT scanners with the xenon/CBF capability. It yields CBV values expressed in milliliters of blood per 100 grams of tissue.

The method was validated under controlled physiological conditions causing changes that were determined both with our technique and from pressure-volume index (PVI) measurements. The two independent estimates of CBV changes were in agreement within 15%. CBV measurements using this method were carried out in normal volunteers to establish baseline values and to compare with values using the ratio-of-areas method for calculating both CBF and CBV from the dynamic study alone. Average CBV was 5.3 mL/100 g. The method was also applied in 71 patients with severe head injuries and in 1 patient with hemodynamic TIAs.

The primary conclusions from this study were (1) the proposed method for measuring CBV accurately determines changes in CBV; (2) the MTT x CBF determinations are in agreement with the ratio-of-areas method for CBV measurements in normal volunteers and are consistent with other methods reported in the literature; (3) MTTs are significantly prolonged early after severe head injury, which when combined with the finding of decreased CBF and increased arteriovenous difference of oxygen indicates increased cerebrovascular resistance due to narrowing of the microcirculation consistent with the presence of early ischemia; and (4) CBV in the patient with TIAs was increased in the hemisphere with the occluded internal carotid artery, indicating compensatory vasodilation and probable hemodynamic cause.

Cerebrovascular vasomotor reactivity reflects changes in smooth muscle tone in the arterial wall in response to changes in transmural pressure or the concentration of carbon dioxide in blood. We investigated whether slow waves in arterial blood pressure (ABP) and intracranial pressure (ICP) may be used to derive an index that reflects the reactivity of vessels to changes in ABP.

A method for the continuous monitoring of the association between slow spontaneous waves in ICP and arterial pressure was adopted in a group of 82 patients with head injuries. ABP, ICP, and transcranial doppler blood flow velocity in the middle cerebral artery was recorded daily (20- to 120-min time periods). A Pressure-Reactivity Index (PRx) was calculated as a moving correlation coefficient between 40 consecutive samples of values for ICP and ABP averaged for a period of 5 seconds. A moving correlation coefficient (Mean Index) between spontaneous fluctuations of mean flow velocity and cerebral perfusion pressure, which was previously reported to describe cerebral blood flow autoregulation, was also calculated.

A positive PRx correlated with high ICP (r = 0.366; P < 0.001), low admission Glasgow Coma Scale score (r = 0.29; P < 0.01), and poor outcome at 6 months after injury (r = 0.48; P < 0.00001). During the first 2 days after injury, PRx was positive (P < 0.05), although only in patients with unfavorable outcomes. The correlation between PRx and Mean index (r = 0.63) was highly significant (P < 0.000001).

Computer analysis of slow waves in ABP and ICP is able to provide a continuous index of cerebrovascular reactivity to changes in arterial pressure, which is of prognostic significance.

The transient hyperemic response test has been shown to provide an index of cerebral autoregulation in healthy individuals and in patients who have suffered a subarachnoid hemorrhage. In this study, the test was applied to patients who had received a severe head injury, and the value of the test was assessed by comparing its result with the individual's clinical condition (Glasgow Coma Scale [GCS] score), cerebral perfusion pressure (CPP), transcranial Doppler wave form-derived index for cerebral autoregulation (relationship between the CPP and the middle cerebral artery flow velocity), and outcome (Glasgow Outcome Scale [GOS] score). Forty-seven patients, aged 16 to 63 years, with head injuries were included in the study. Signals of intracranial pressure, arterial blood pressure, flow velocity, and cortical microcirculatory flux were digitized and recorded for a period of 30 minutes using special computer software. Two carotid compressions were performed at the beginning of each recording. The transient hyperemic response ratio (THRR: the ratio of the hyperemic flow velocity recorded after carotid release and the precompression baseline flow velocity) was calculated, as was the correlation coefficient Sx used to describe the relationship between slow fluctuations in the systolic flow velocity and CPP throughout the period of recording. No significant changes in CPP were found during compression. There was a significant correlation between the THRR and the Sx (r = 0.49, p < 0.0001). The hyperemic response proved to be lower in patients who exhibited a poor clinical grade at presentation (GCS scores < 6, p = 0.01) and lower in patients achieving a poor outcome (GOS scores of 3, 4, and 5, p = 0.003). Loss of postcompression hyperemia occurred when the CPP fell below 50 mm Hg. The carotid compression test provides a simple index of cerebral autoregulation that is relevant to the clinical condition and outcome of the severely head injured patient.

Cerebrovascular carbon dioxide (CO2) reactivity is an important hemodynamic index in cerebrovascular disease. In the present study T2*-weighted magnetic resonance image (T2* WI) was evaluated as a non-invasive method to investigate changes in CO2 reactivity. Fourteen rats were subjected to permanent or, 30 and 90 min of temporary middle cerebral artery occlusion. A series of T2* WIs and diffusion-weighted magnetic resonance images (DWI) was performed hourly under normo- and hypercapnic conditions. Triphenyltetrazolium chloride (TTC) staining of brain sections was obtained at the end of experiment to evaluate ischemic damage. During ischemia, a 4-6% signal increase upon hypercapnia was observed on T2* WI in the non-ischemic hemisphere, while no such reactivity was seen in the putamen and cortex ipsilateral to the MCA occlusion. After reperfusion, CO2 reactivity recovered in the putamen and cortex in the 30 min ischemia group and in the cortex alone of the 90 min ischemia groups. The areas with irreversible CO2 reactivity dysfunction coincidentally revealed no recovery on DWI and lack of TTC staining. The results indicate that T2* WI can be used to monitor changes in CO2 reactivity after various ischemic insults that may indicate tissue viability.

This report provides findings of an investigation of the influence of traumatic subarachnoid hemorrhage on the development of delayed cerebral ischemia caused by vasospasm. The authors prospectively studied 130 patients with closed-head trauma, who exhibited subarachnoid blood on admission computerized tomography (CT) scans. Ten (7.7%) of these patients developed delayed ischemic symptoms between Days 4 and 16 after the head injury. They consisted of three (3.0%) of 101 patients with small amounts of subarachnoid blood and seven (24.1%) of 29 patients with massive quantities of subarachnoid blood on admission CT scans. In each of the 10 patients, severe vasospasm was demonstrated by angiography performed soon after development of ischemic symptoms. There was a close correlation between the main site of the subarachnoid blood and the location of severe vasospasm. In seven of the patients, follow-up CT scans showed development of focal ischemic areas in the cerebral territories corresponding to the vasospastic arteries. These results demonstrate that traumatic subarachnoid hemorrhage, especially if massive, is a predictable indicator of delayed ischemic symptoms.