A Narrative Review on Financial Challenges and Health Care Costs Associated with Traumatic Brain Injury in the United States.

BACKGROUND: Traumatic brain injury (TBI) is a highly prevalent and potentially severe medical condition. Challenges regarding TBI management are related to accurate diagnostics, defining its severity, and establishing prompt interventions to affect outcomes. Among the health care components in the TBI handling strategy is intracranial pressure (ICP) monitoring, which is fundamental to therapy decisions. However, ICP monitoring is an Achilles tendon, imposing a significant financial burden on health care systems, particularly in middle and low-income communities. This article arises from the understanding from the authors that there is insufficient scientific evidence about the potential economic impacts from the use of noninvasive technologies in the monitoring of TBI. Based on personal experience, as well as from reading other, clinically focused studies, the thesis is that the use of such technologies could greatly affect the health care system and this article seeks to address this lack of literature, show ways in which such systems could be evaluated, and show estimations of possible results from these investigations. OBJECTIVE: This review primarily investigates the economic burden of TBI and whether new technologies are suitable to reduce its health care costs without compromising the quality of care, according to the levels of evidence available. The objective is to stimulate more research and attention in the area. METHODS: For this narrative review, a PubMed search was conducted for articles discussing TBI health care costs, as well as monitoring technologies (tomography, magnetic resonance imaging, optic nerve sheath diameter, transcranial Doppler, pupillometry, and noninvasive ICP waveform) and their application in managing TBI. Strategies were first evaluated from a medical noninferiority perspective before calculating the average savings of each selected strategy. All applicable studies were analyzed for quality using the Consolidated Health Economic Evaluation Reporting Standards 2022 Statement117 and this article was written to conform as much as possible with it. RESULTS: The review included 109 references and showed a consistent potential in noninvasive technologies to reduce costs and maintain or improve the quality of care. CONCLUSIONS: TBI prevalence has increased with a disproportionate health care burden in the last decades. Noninvasive monitoring techniques seem to be effective in reducing TBI health care costs, with few limitations, especially the need for more supporting scientific evidence. The undeniable clinical and financial potential of these techniques is compelling to further investigate their role in TBI management, as well as the creation of more comprehensive monitoring models to the understanding of complex phenomena occurring in the injured brain.

Perfusion tomography in early follow-up of acute traumatic subdural hematoma: a case series.

Perfusion Computed Tomography (PCT) is an alternative tool to assess cerebral hemodynamics during trauma. As acute traumatic subdural hematomas (ASH) is a severe primary injury associated with poor outcomes, the aim of this study was to evaluate the cerebral hemodynamics in this context. Five adult patients with moderate and severe traumatic brain injury (TBI) and ASH were included. All individuals were indicated for surgical evacuation. Before and after surgery, PCT was performed and cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were evaluated. These parameters were associated with the outcome at 6 months post-trauma with the extended Glasgow Outcome Scale (GOSE). Mean age of population was 46 years (SD: 8.1). Mean post-resuscitation Glasgow coma scale (GCS) was 10 (SD: 3.4). Mean preoperative midline brain shift was 10.1 mm (SD: 1.8). Preoperative CBF and MTT were 23.9 ml/100 g/min (SD: 6.1) and 7.3 s (1.3) respectively. After surgery, CBF increase to 30.7 ml/100 g/min (SD: 5.1), and MTT decrease to 5.8s (SD:1.0), however, both changes don't achieve statistically significance (p = 0.06). Additionally, CBV increase after surgery, from 2.34 (SD: 0.67) to 2.63 ml/100 g (SD: 1.10), (p = 0.31). Spearman correlation test of postoperative and preoperative CBF ratio with outcome at 6 months was 0.94 (p = 0.054). One patient died with the highest preoperative MTT (9.97 s) and CBV (4.51 ml/100 g). CBF seems to increase after surgery, especially when evaluated together with the MTT values. It is suggested that the improvement in postoperative brain hemodynamics correlates to favorable outcome.

ICP wave morphology as a screening test to exclude intracranial hypertension in brain-injured patients: a non-invasive perspective.

Intracranial hypertension (IH) is a life-threating condition especially for the brain injured patient. In such cases, an external ventricular drain (EVD) or an intraparenchymal bolt are the conventional gold standard for intracranial pressure (ICPi) monitoring. However, these techniques have several limitations. Therefore, identifying an ideal screening method for IH is important to avoid the unnecessary placement of ICPi and expedite its introduction in patients who require it. A potential screening tool is the ICP wave morphology (ICPW) which changes according to the intracranial volume-pressure curve. Specifically, the P2/P1 ratio of the ICPW has shown promise as a triage test to indicate normal ICP. In this study, we propose evaluating the noninvasive ICPW (nICPW-B4C sensor) as a screening method for ICPi monitoring in patients with moderate to high probability of IH. This is a retrospective analysis of a prospective, multicenter study that recruited adult patients requiring ICPi monitoring from both Federal University of São Paulo and University of São Paulo Medical School Hospitals. ICPi values and the nICPW parameters were obtained from both the invasive and the noninvasive methods simultaneously 5 min after the closure of the EVD drainage. ICP assessment was performed using a catheter inserted into the ventricle and connected to a pressure transducer and a drainage system. The B4C sensor was positioned on the patient's scalp without the need for trichotomy, surgical incision or trepanation, and the morphology of the ICP waves acquired through a strain sensor that can detect and monitor skull bone deformations caused by changes in ICP. All patients were monitored using this noninvasive system for at least 10 min per session. The area under the curve (AUC) was used to describe discriminatory power of the P2/P1 ratio for IH, with emphasis in the Negative Predictive value (NPV), based on the Youden index, and the negative likelihood ratio [LR-]. Recruitment occurred from August 2017 to March 2020. A total of 69 patients fulfilled inclusion and exclusion criteria in the two centers and a total of 111 monitorizations were performed. The mean P2/P1 ratio value in the sample was 1.12. The mean P2/P1 value in the no IH population was 1.01 meanwhile in the IH population was 1.32 (p < 0.01). The best Youden index for the mean P2/P1 ratio was with a cut-off value of 1.13 showing a sensitivity of 93%, specificity of 60%, and a NPV of 97%, as well as an AUC of 0.83 to predict IH. With the 1.13 cut-off value for P2/P1 ratio, the LR- for IH was 0.11, corresponding to a strong performance in ruling out the condition (IH), with an approximate 45% reduction in condition probability after a negative test (ICPW). To conclude, the P2/P1 ratio of the noninvasive ICP waveform showed in this study a high Negative Predictive Value and Likelihood Ratio in different acute neurological conditions to rule out IH. As a result, this parameter may be beneficial in situations where invasive methods are not feasible or unavailable and to screen high-risk patients for potential invasive ICP monitoring.Trial registration: At clinicaltrials.gov under numbers NCT05121155 (Registered 16 November 2021-retrospectively registered) and NCT03144219 (Registered 30 September 2022-retrospectively registered).

Transcranial Doppler and Color-Coded Doppler Use for Brain Death Determination in Adult Patients: A Pictorial Essay.

Transcranial Doppler (TCD) is a repeatable, at-the-bedside, helpful tool for confirming cerebral circulatory arrest (CCA). Despite its variable accuracy, TCD is increasingly used during brain death determination, and it is considered among the optional ancillary tests in several countries. Among its limitations, the need for skilled operators with appropriate knowledge of typical CCA patterns and the lack of adequate acoustic bone windows for intracranial arteries assessment are critical. The purpose of this review is to describe how to evaluate cerebral circulatory arrest in the intensive care unit with TCD and transcranial duplex color-coded doppler (TCCD).

Improved Transcranial Doppler Waveform Analysis for Intracranial Hypertension Assessment in Patients with Traumatic Brain Injury.

BACKGROUND: Transcranial Doppler (TCD) is a noninvasive bedside tool for cerebral hemodynamic assessments in multiple clinical scenarios. TCD, by means of measuring systolic and diastolic blood velocities, allows the calculation of the pulsatility index (PI), a parameter that is correlated with intracranial pressure (ICP). Nevertheless, the predictive value of the PI for raised ICP appears to be low, as it is subjected to several, often confounding, factors not related to ICP. Recently, the pulsatile apparent resistance (PaR) index was developed as a PI corrected for arterial blood pressure, reducing some of the confounding factors influencing PI. This study compares the predictive value of PaR versus PI for intracranial hypertension (IH) (ICP > 20 mm Hg) in patients with traumatic brain injury. METHODS: Patients with traumatic brain injury admitted to the neurocritical care unit who required invasive ICP monitoring were included prospectively within 5 days of admission. TCD measurements were performed in both middle cerebral arteries, allowing calculations of the PI and PaR. The optimal cutoff, discriminative power of these parameters for ICP ≥ 20 mm Hg, was assessed by calculating the area under the receiver operator characteristics curve (AUC). RESULTS: In total, 93 patients were included. A total of 20 (22%) patients experienced IH during the recording sessions. The discriminative power was low for PI (AUC 0.63) but slightly higher for PaR (AUC 0.77). Nonparametric analysis indicated significant difference for PaR when comparing patients with (median 0.169) and without IH (median - 0.052, p = 0.001), whereas PI medians for patients with and without IH were 0.86 and 0.77, respectively (p = 0.041). Regarding subanalyses, the discriminative power of these parameters increased after exclusion of patients who had undergone a neurosurgical procedure. This was especially true for the PaR (AUC 0.89) and PI (AUC 0.72). Among these patients, a PaR cutoff value of - 0.023 had 100% sensitivity and 52.9% specificity. CONCLUSIONS: In the present study, discriminative power of the PaR for discriminating IH was superior to the PI. The PaR seems to be a reliable noninvasive parameter for detecting IH. Further studies are warranted to define its clinical application, especially in aiding neurosurgical decision making, following up in intensive care units, and defining its ability to indicate responses according to the therapies administered.

Intracranial compliance and volumetry in patients with traumatic brain injury.

Background: Cerebral edema (CE) and intracranial hypertension (IHT) are complications of numerous neurological pathologies. However, the study of CE and noninvasive methods to predict IHT remains rudimentary. This study aims to identify in traumatic brain injury (TBI) patients the relationship between the volume of the lateral ventricles and the parameters of the noninvasive intracranial pressure waveform (nICPW). Methods: This is an analytical, descriptive, and cross-sectional study with nonsurgical TBI patients. The monitoring of nICPW was performed with a mechanical strain gauge, and the volumetry of the lateral ventricles was calculated using the free 3D Slicer software, both during the acute phase of the injury. The linear model of fixed and random mixed effects with Gamma was used to calculate the influence of nICPW parameters (P2/P1 and time-to-peak [TTP]) values on volumetry. Results: Considering only the fixed effects of the sample, there was P = 0.727 (95% CI [-0.653; 0.364]) for the relationship between P2/P1 and volumetry and 0.727 (95% CI [-1.657; 1.305]) for TTP and volumetry. Considering the fixed and random effects, there was P = 8.5e-10 (95% CI [-0.759; 0.355]) for the relationship between P2/P1 and volumetry and 8.5e-10 (95% CI [-2.001; 0.274]) for TTP and volumetry. Conclusion: The present study with TBI patients found association between nICPW parameters and the volume of the lateral ventricles in the 1st days after injury.

Point-Counterpoint: Cerebral perfusion pressure is a high-risk concept.

Cerebral perfusion pressure (CPP) is calculated as the difference between mean arterial blood pressure and mean intracranial pressure, being commonly applied in neurocritical care. This commentary discusses recent physiological advances in knowledge as well as bedside practice issues that in combination indicate considering CPP under this perspective may lead to inaccurate assumptions and potentially misleading decision making.

Doing More with Less on Intracranial Pressure Monitoring.

BACKGROUND: Intracranial pressure (ICP) management based on predetermined thresholds is not accurate in light of recent research on cerebrovascular physiology. Interpersonal and intrapersonal variations will lead ICP elevations to reach individualized thresholds for intracranial compliance impairment from one subject to another. Therefore reuniting the modern techniques of neuromonitoring besides ICP enables practitioners to have a more whole picture in anticipating neuro worsening and improving timing in decision making. METHODS: Brief literature review. RESULTS: For the severely brain-injured patient, current evidence indicates a personalized and physiology-based multimodal monitoring care to be required rather than decision making according to ICP predetermined cut-offs. CONCLUSIONS: The authors' point of view is of particular importance for regions with resource heterogeneity and scarcity, where ICP monitoring is not available for all those in need and noninvasive techniques may provide a surrogate approach. If physicians who deal with acute-brain-injured patients in lower-resource areas understand that several tools besides ICP may improve their practice, it is possible to reduce acute brain injury morbimortality.

Immunomodulatory response in an experimental model of brain death.

Liver transplantation has come a long way and is now regarded as the gold standard treatment for end-stage liver failure. The great majority of livers utilized in transplantation come from brain-dead donors. A broad inflammatory response characterizes BD, resulting in multiorgan damage. This process is primarily mediated by cytokines, which increase the immunogenicity of the graft. In male Lewis rats, we evaluated the immune response in a BD liver donor and compared it to that of a control group. We studied two groups: Control and BD (rats subjected to BD by increasing intracranial pressure). After the induction of BD, there was an intense rise in blood pressure followed by a fall. There were no significant differences observed between the groups. Blood tissue and hepatic tissue analyzes showed an increase in plasma concentrations of liver enzymes (AST, ALT, LDH and ALP), in addition to pro-inflammatory cytokines and macrophages in liver tissue in animals submitted to BD. The current study found that BD is a multifaceted process that elicits both a systemic immune response and a local inflammatory response in liver tissue. Our findings strongly suggested that the immunogenicity of plasma and liver increased with time following BD.

The intracranial compartmental syndrome: a proposed model for acute brain injury monitoring and management.

For decades, one of the main targets in the management of severe acute brain injury (ABI) has been intracranial hypertension (IH) control. However, the determination of IH has suffered variations in its thresholds over time without clear evidence for it. Meanwhile, progress in the understanding of intracranial content (brain, blood and cerebrospinal fluid) dynamics and recent development in monitoring techniques suggest that targeting intracranial compliance (ICC) could be a more reliable approach rather than guiding actions by predetermined intracranial pressure values. It is known that ICC impairment forecasts IH, as intracranial volume may rapidly increase inside the skull, a closed bony box with derisory expansibility. Therefore, an intracranial compartmental syndrome (ICCS) can occur with deleterious brain effects, precipitating a reduction in brain perfusion, thereby inducing brain ischemia. The present perspective review aims to discuss the ICCS concept and suggest an integrative model for the combination of modern invasive and noninvasive techniques for IH and ICC assessment. The theory and logic suggest that the combination of multiple ancillary methods may enhance ICC impairment prediction, pointing proactive actions and improving patient outcomes.

Qualitative Evaluation of Intracranial Pressure Slopes in Patients Undergoing Brain Death Protocol.

BACKGROUND: Due to the importance of not mistaking when determining the brain death (BD) diagnostic, reliable confirmatory exams should be performed to enhance its security. This study aims to evaluate the intracranial pressure (ICP) pulse morphology behavior in brain-dead patients through a noninvasive monitoring system. METHODS: A pilot case-control study was conducted in adults that met the BD national protocol criteria. Quantitative parameters from the ICP waveforms, such as the P2/P1 ratio, time-to-peak (TTP) and pulse amplitude (AMP) were extracted and analyzed comparing BD patients and health subjects. RESULTS: Fifteen patients were included, and 6172 waveforms were analyzed. ICP waveforms presented substantial differences amidst BD patients when compared to the control group, especially AMP, which had lower values in patients diagnosed with BD (p < 0.0001) and the TTP median (p < 0.00001), but no significance was found for the P2/P1 ratio (p = 0.8). The area under curve for combination of parameters on the BD prediction was 0.77. CONCLUSIONS: In this exploratory study, noninvasive ICP waveforms have shown potential as a screening method in patients with suspected brain death. Future studies should be carried out in a larger population.

Critical Closing Pressure and Cerebrovascular Resistance Responses to Intracranial Pressure Variations in Neurocritical Patients.

BACKGROUND: Critical closing pressure (CrCP) and resistance-area product (RAP) have been conceived as compasses to optimize cerebral perfusion pressure (CPP) and monitor cerebrovascular resistance, respectively. However, for patients with acute brain injury (ABI), the impact of intracranial pressure (ICP) variability on these variables is poorly understood. The present study evaluates the effects of a controlled ICP variation on CrCP and RAP among patients with ABI. METHODS: Consecutive neurocritical patients with ICP monitoring were included along with transcranial Doppler and invasive arterial blood pressure monitoring. Internal jugular veins compression was performed for 60 s for the elevation of intracranial blood volume and ICP. Patients were separated in groups according to previous intracranial hypertension severity, with either no skull opening (Sk1), neurosurgical mass lesions evacuation, or decompressive craniectomy (DC) (patients with DC [Sk3]). RESULTS: Among 98 included patients, the correlation between change (Δ) in ICP and the corresponding ΔCrCP was strong (group Sk1 r = 0.643 [p = 0.0007], group with neurosurgical mass lesions evacuation r = 0.732 [p < 0.0001], and group Sk3 r = 0.580 [p = 0.003], respectively). Patients from group Sk3 presented a significantly higher ΔRAP (p = 0.005); however, for this group, a higher response in mean arterial pressure (change in mean arterial pressure p = 0.034) was observed. Exclusively, group Sk1 disclosed reduction in ICP before internal jugular veins compression withholding. CONCLUSIONS: This study elucidates that CrCP reliably changes in accordance with ICP, being useful to indicate ideal CPP in neurocritical settings. In the early days after DC, cerebrovascular resistance seems to remain elevated, despite exacerbated arterial blood pressure responses in efforts to maintain CPP stable. Patients with ABI with no need of surgical procedures appear to remain with more effective ICP compensatory mechanisms when compared with those who underwent neurosurgical interventions.

Clinical and histopathology characteristics of Castleman disease: a multicenter study of 51 Brazilian patients.

Castleman's disease (CD) is a rare and heterogeneous lymphoproliferative disorder, with limited available clinical information in Brazil. A retrospective study was carried out through information contained in the medical records of 51 patients, between July 1999 and June 2020. Seven patients were excluded, and 44 were analyzed in total. The average age of unicentric CD (UCD) patients was 35 years old and of multicentric CD (MCD) patients was 49 years old (p = 0.013). Regarding gender, there was a predominance of females among patients with UCD (68.4%) and males in patients with MCD (57.9%) (p = 0.103). The most common site of involvement in UCD was the cervical region (36.8%). A total of 73.7% of patients with UCD and 68.4% of patients with MCD presented the histological form hialyne-vascular (HV) (p = 0.499). Most patients with laboratory abnormalities had MCD. A total of 78% of the patients were asymptomatic, with the majority of symptomatic patients with MCD (p = 0.042). Only two of the 27 patients evaluated for the presence of human immunodeficiency virus (HIV) had positive serology. HHV-8 was evaluated in 14 cases, being positive in two. Of the patients with UCD, 94.7% underwent excisional biopsy, against only 41.2% of patients with MCD (p = 0.01). The mean follow-up was 61 months. We observed similarities in the clinical profile between patients in our study and patients described in the literature, such as gender, mean age, B symptoms, visceromegaly, fluid accumulation, and treatment. Unlike the literature, the cervical region was the most affected site, besides the greater association of the HV histological subtype among patients with MCD.

Noninvasive intracranial pressure waveforms for estimation of intracranial hypertension and outcome prediction in acute brain-injured patients.

Analysis of intracranial pressure waveforms (ICPW) provides information on intracranial compliance. We aimed to assess the correlation between noninvasive ICPW (NICPW) and invasively measured intracranial pressure (ICP) and to assess the NICPW prognostic value in this population. In this cohort, acute brain-injured (ABI) patients were included within 5 days from admission in six Intensive Care Units. Mean ICP (mICP) values and the P2/P1 ratio derived from NICPW were analyzed and correlated with outcome, which was defined as: (a) early death (ED); survivors on spontaneous breathing (SB) or survivors on mechanical ventilation (MV) at 7 days from inclusion. Intracranial hypertension (IHT) was defined by ICP > 20 mmHg. A total of 72 patients were included (mean age 39, 68% TBI). mICP and P2/P1 values were significantly correlated (r = 0.49, p < 0.001). P2/P1 ratio was significantly higher in patients with IHT and had an area under the receiving operator curve (AUROC) to predict IHT of 0.88 (95% CI 0.78-0.98). mICP and P2/P1 ratio was also significantly higher for ED group (n = 10) than the other groups. The AUROC of P2/P1 to predict ED was 0.71 [95% CI 0.53-0.87], and the threshold P2/P1 > 1.2 showed a sensitivity of 60% [95% CI 31-83%] and a specificity of 69% [95% CI 57-79%]. Similar results were observed when decompressive craniectomy patients were excluded. In this study, P2/P1 derived from noninvasive ICPW assessment was well correlated with IHT. This information seems to be as associated with ABI patients outcomes as ICP.Trial registration: NCT03144219, Registered 01 May 2017 Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT03144219 .