Quantitative analysis of apparent diffusion coefficients to predict neurological prognosis in cardiac arrest survivors: an observational derivation and internal-external validation study.

BACKGROUND: This study aimed to validate apparent diffusion coefficient (ADC) values and thresholds to predict poor neurological outcomes in out-of-hospital cardiac arrest (OHCA) survivors by quantitatively analysing the ADC values via brain magnetic resonance imaging (MRI). METHODS: This observational study used prospectively collected data from two tertiary academic hospitals. The derivation cohort comprised 70% of the patients randomly selected from one hospital, whereas the internal validation cohort comprised the remaining 30%. The external validation cohort used the data from another hospital, and the MRI data were restricted to scans conducted at 3 T within 72-96 h after an OHCA experience. We analysed the percentage of brain volume below a specific ADC value at 50-step intervals ranging from 200 to 1200 × 10-6 mm2/s, identifying thresholds that differentiate between good and poor outcomes. Poor neurological outcomes were defined as cerebral performance categories 3-5, 6 months after experiencing an OHCA. RESULTS: A total of 448 brain MRI scans were evaluated, including a derivation cohort (n = 224) and internal/external validation cohorts (n = 96/128, respectively). The proportion of brain volume with ADC values below 450, 500, 550, 600, and 650 × 10-6 mm2/s demonstrated good to excellent performance in predicting poor neurological outcomes in the derivation group (area under the curve [AUC] 0.89-0.91), and there were no statistically significant differences in performances among the derivation, internal validation, and external validation groups (all P > 0.5). Among these, the proportion of brain volume with an ADC below 600 × 10-6 mm2/s predicted a poor outcome with a 0% false-positive rate (FPR) and 76% (95% confidence interval [CI] 68-83) sensitivity at a threshold of > 13.2% in the derivation cohort. In both the internal and external validation cohorts, when using the same threshold, a specificity of 100% corresponded to sensitivities of 71% (95% CI 58-81) and 78% (95% CI 66-87), respectively. CONCLUSIONS: In this validation study, by consistently restricting the MRI types and timing during quantitative analysis of ADC values in brain MRI, we observed high reproducibility and sensitivity at a 0% FPR. Prospective multicentre studies are necessary to validate these findings.

The agreement between jugular bulb and cerebrospinal fluid lactate levels in patients with out-of-hospital cardiac arrest.

We investigated the agreement between the jugular bulb (JB) and cerebrospinal fluid (CSF) lactate levels. The study was conducted from July 2021 to June 2023 as a prospective observational cohort study at a single center. The right jugular vein was accessed, and the placement of JB catheter tip was confirmed using lateral cervical spine X-ray. A lumbar catheter was inserted between the 3rd and 4th lumbar spine of the patient. Lactate levels were measured immediately, 24 h, 48 h, and 72 h after ROSC. In patients with a good neurological prognosis, kappa between JB and CSF lactate levels measured immediately, at 24 h, 48 h, and 72 h after ROSC were 0.08, 0.36, 0.14, - 0.05 (p = 0.65, 0.06, 0.48, and 0.75, respectively). However, in patients with a poor neurological prognosis, kappa between JB and CSF lactate levels measured immediately, at 24 h, 48 h, and 72 h after ROSC were 0.38, 0.21, 0.22, 0.12 (p = 0.001, 0.04, 0.04, and 0.27, respectively). This study demonstrated that JB lactate levels exhibited significant agreement with arterial lactate levels, compared to CSF lactate levels. Therefore, this should be considered when using JB lactate to monitor cerebral metabolism.

Cerebrospinal Fluid Dynamics and Partial Pressure of Carbon Dioxide as Prognostic Indicators in Hypoxic-Ischemic Brain Injury Following Cardiac Arrest.

Changes in cerebrospinal fluid (CSF) dynamics can have adverse effects on neuronal function. We hypothesized that patients with hypoxic-ischemic brain injury (HIBI) showing poor neurological outcomes after cardiac arrest (CA) would exhibit changes in CSF dynamics, leading to abnormalities in gas diffusion within the CSF. Therefore, we investigated the prognostic value of the CSF partial pressure of carbon dioxide (PcsfCO2) in CA survivors who underwent targeted temperature management (TTM). We retrospectively analyzed the 6-month neurological outcomes, CSF, and arterial blood gas parameters of 67 CA survivors. Patients were divided into good and poor neurological outcome groups, and the predictive value of PcsfCO2 for poor neurological outcomes was assessed using receiver operating characteristic curve analysis. Among all patients, 39 (58.2%) had poor neurological outcomes. Significant differences in PcsfCO2 levels between the groups were observed, with lower PcsfCO2 levels on Day 1 showing the highest predictive value at a cutoff of 30 mmHg (area under the curve, sensitivity, and specificity were 0.823, 77.8%, and 79.0%, respectively). These results suggest that PcsfCO2 might serve not only as a unique marker for the severity of hypoxic-ischemic brain injury (HIBI), independent of extracorporeal CO2 levels, but also as an objective indicator of changes in CSF dynamics. This study highlights the potential prognostic and diagnostic utility of PcsfCO2 during TTM in CA survivors, emphasizing its importance in evaluating CSF dynamics and neurological recovery post CA. However, larger multicenter studies are warranted to address potential limitations associated with sample size and outcome assessment methods.

Distribution and elimination kinetics of midazolam and metabolites after post-resuscitation care: a prospective observational study.

Administration of sedatives for post-resuscitation care can complicate the determination of the optimal timing to avoid inappropriate, pessimistic prognostications. This prospective study aimed to investigate the distribution and elimination kinetics of midazolam (MDZ) and its metabolites, and their association with awakening time. The concentrations of MDZ and its seven metabolites were measured immediately and at 4, 8, 12, and 24 h after the discontinuation of MDZ infusion, using liquid chromatography-tandem mass spectrometry. The area under the time-plasma concentration curve from 0 to 24 h after MDZ discontinuation (AUClast) was calculated based on the trapezoidal rule. Of the 15 enrolled patients, seven awakened after the discontinuation of MDZ infusion. MDZ and three of its metabolites were major compounds and their elimination kinetics followed a first-order elimination profile. In the multivariable analysis, only MDZ was associated with awakening time (AUClast: R2 = 0.59, p = 0.03; AUCinf: R2 = 0.96, p < 0.001). Specifically, a 0.001% increase in MDZ AUC was associated with a 1% increase in awakening time. In the individual regression analysis between MDZ concentration and awakening time, the mean MDZ concentration at awakening time was 16.8 ng/mL. The AUC of MDZ is the only significant factor associated with the awakening time.

Blood-brain barrier permeability for the first 24 hours in hypoxic-ischemic brain injury following cardiac arrest.

BACKGROUND: This study aimed to explore the changes in blood-brain barrier (BBB) permeability and intracranial pressure (ICP) for the first 24 h after the return of spontaneous circulation (ROSC) and their association with injury severity of cardiac arrest. METHODS: This prospective study analysed the BBB permeability assessed using the albumin quotient (Qa) and ICP every 2 h for the first 24 h after ROSC. The injury severity of cardiac arrest was assessed using Pittsburgh Cardiac Arrest Category (PCAC) scores. The primary outcome was the time course of changes in the BBB permeability and ICP for the first 24 h after ROSC and their association with injury severity (PCAC scores of 1-4). RESULTS: Qa and ICP were measured 274 and 197 times, respectively, in 32 enrolled patients. Overall, the BBB permeability increased progressively over time after ROSC, and then it increased significantly at 18 h after ROSC compared with the baseline. In contrast, the ICP revealed non-significant changes for the first 24 h after ROSC. The Qa in the PCAC 2 group was < 0.01, indicating normal or mild BBB disruption at all time points, whereas the PCAC 3 and 4 groups showed a significant increase in BBB permeability at 14 and 22 h, and 12 and 14 h after ROSC, respectively. CONCLUSION: BBB permeability increased progressively over time for the first 24 h after ROSC despite post-resuscitation care, whereas ICP did not change over time. BBB permeability has an individual pattern when stratified by injury severity.

Comparison of modified quick sequential organ failure assessment models as triage tools for febrile patients.

Object: Effective triage of febrile patients in the emergency department is crucial during times of overcrowding to prioritize care and allocate resources, especially during pandemics. However, available triage tools often require laboratory data and lack accuracy. We aimed to develop a simple and accurate triage tool for febrile patients by modifying the qSOFA score. Methods: We retrospectively analyzed data from 7,303 febrile patients and created modified versions of qSOFA using factors identified through multivariable analysis. The performance of these modified qSOFAs in predicting in hospital mortality and intensive care unit (ICU) admission was compared using the area under the receiver operating characteristic curve (AUROC). Results: Through multivariable analysis, the identified factors were age (A), male sex (M), SpO2 (S), and lactate levels (L). The AUROCs of ASqSOFA (for in-hospital mortality: 0.812; 95% CI: 0.789-0.835, for ICU admission: 0.794; 95% CI: 0.771-0.817), which included age and SpO2 with qSOFA, were simple and not inferior to other more complex models (e.g., ASMqSOFA, ASLqSOFA, and ASMLqSOFA). ASqSOFA also displayed significantly higher AUROC than other triage scales, such as the modified early warning score and Korean triage and acuity scale. The optimal cut-off score of ASqSOFA for the outcome was 2 and the score for redistribution to a lower-level emergency department was 0. Conclusion: We demonstrated that ASqSOFA can be employed as a simple and efficient triage tool for emergency febrile patients to aid in resource distribution during overcrowding. It may also be applicable in pre-hospital settings for febrile patient triage.