Intensive Care Medicine Experimental最新文献

Animal models of critical illness span diverse species and experimental approaches, reflecting the biological complexity of severe disease states while being constrained by animal welfare requirements and country-specific regulatory, infrastructural, and workforce factors. Persistent challenges remain, including limited reproducibility, fragmented standards, and the need for ethical alignment across borders. This review examines these shared structural challenges in critical illness animal research across the Asia-Pacific region. While alternative and complementary methodologies are increasingly incorporated into preclinical research, their adoption remains uneven. We argue that alignment with globally recognized preclinical frameworks, including the 3Rs and disease-specific standards, such as MQTiPSS, is essential. This review discusses actionable strategies-centered on harmonized standards, shared resources, and international collaboration-to strengthen research rigor, support early career researchers, and enhance the translational relevance of critical illness animal research.

Background: Venovenous extracorporeal membrane oxygenation (ECMO) is essential for patients with severe respiratory failure who do not respond to conventional mechanical ventilation. Adequate ECMO flow and safe circuit pressure are critical; however, cannula selection, which has a great impact on these factors, is often based on empirical judgment. This study aimed to develop a simple predictive method based on fluid dynamics for estimating ECMO flow rate and circuit pressures (P1: pre-pump, P2: pre-oxygenator, and P3: post-oxygenator). This experimental predictive model study compared the calculated and measured ECMO parameters across 36 combinations of cannula sizes, pump speeds, and bed heights. A laboratory-based ECMO circuit model was assembled with various drainage and return cannulas, an oxygenator, tubing, and a centrifugal pump. The circuit was primed with a 33% glycerin solution and tested across the 36 combinations. A four-step prediction method was applied: (1) modeling the pressure-flow relationships of ECMO components and the pump using manufacturer data; (2) identifying the expected flow rate by locating the intersection of the total circuit resistance and pump output curves; (3) sequentially calculating pressure drops across the circuit; and (4) adjusting pressures based on bed height.

Results: The predicted flow rate and circuit pressure values were compared to experimental measurements across the 36 combinations. The calculated and measured values showed strong agreement (R² = 0.96-0.97), and predictions were significant. Notably, bed height alterations were confirmed to affect circuit pressure but not flow rate.

Conclusions: Our newly developed method reliably predicts the ECMO flow rate and circuit pressure. Hence, it can be considered a valuable tool for preemptively selecting the optimal cannula size for ECMO, thus improving patient safety and circuit management. Furthermore, it may be a valuable educational tool, making complex hemodynamic concepts more intuitive for trainees.

Background: Mechanical ventilation typically utilizes positive-pressure ventilation (PPV), which fundamentally differs from physiological pressure conditions. In contrast, negative-pressure ventilation (NPV) more closely mimics physiological pressure conditions; however, its impact on ventilation-perfusion matching remains unclear. Therefore, we compared PPV and NPV in terms of their effects on ventilation-perfusion matching and determined the consequences of increasing end-expiratory pressure (EEP).

Methods: Anesthetized rats (n = 9) were ventilated using PPV at a positive EEP of 0, 3, 6, and 9 cmH₂O. NPV was initiated by placing the rats in a sealed chamber and generating cyclic negative-pressure changes around the body while maintaining identical EEP and tidal volumes. At each EEP level, the arterial partial pressures of oxygen (PaO₂) and CO₂ (PaCO₂) were measured from blood samples. Phase 2 (S2V) and 3 slopes (S3V), Fowler's anatomical dead space fraction (VDF), and physiological dead space fractions according to Bohr (VDB) and Enghoff (VDE) were determined by volumetric capnography.

Results: Higher PaO₂ and lower PaCO₂ were observed during NPV compared with PPV. The lower S2V and S3V values were associated with reduced VDF and VDB during NPV, whereas VDE including alveolar compartments with intrapulmonary shunt was higher. Elevating positive EEP during PPV increased S2V, S3V, and VDB, whereas the same lung expansion with NPV had a smaller effect.

Conclusions: The results indicate that compared with PPV, NPV enhances gas exchange and ventilation-perfusion matching in healthy lungs. Although NPV causes fewer ventilation-perfusion inequalities and reduced dead space ventilation, its efficacy may be limited by increased intrapulmonary shunting during excessive negative end-expiratory pressure levels. These results provide mechanistic support for the physiological benefits of subatmospheric ventilation and may provide a basis for further studies on the refinement of noninvasive and lung-protective ventilation strategies in clinical settings with impaired ventilation-perfusion matching, such as acute respiratory failure, postoperative care, and ventilator weaning.

Background: Traumatic brain injury (TBI) remains a major global health issue, with limited progress in reducing morbidity and mortality for TBI patients in need of sedation and intensive care. This has led to increased focus on the mechanisms of secondary brain injury, typically monitored via high-frequency, multi-modal physiologic data reflecting pressure flow and oxygen delivery. However, the complexity and volume of such data pose challenges for clinicians, leading to the use of resolution-reducing techniques, such as moving averages and point sampling. However, data often remains a challenge to utilize clinically for physiologic insult predications and early or pre-emptive interventions. Time series modeling approaches like autoregressive integrated moving average (ARIMA) are valuable in analyzing statistical signal structures, providing insights into temporal dynamics by revealing temporal patterns and forecasting future physiological states.

Results: This study evaluated the effects of resolution reduction via averaging on point and interval predictions using ARIMA models. Analysis was performed on both raw signals and derived physiologic metrics of cerebral pressure flow, compliance, and oxygen delivery by utilizing the CAnadian High-Resolution TBI (CAHR-TBI) data set. Temporal resolution was reduced by averaging with non-overlapping intervals, ranging from 1-min to 24-h windows. Data from A total of 376 TBI patients requiring intensive care was analyzed across various temporal resolutions. ARIMA models perform best at high temporal resolutions, particularly for derived cerebrovascular reactivity indices, with accuracy decreasing for raw signals at lower resolutions. The choice of data partitioning method affects performance; however, all methods struggle at the lowest resolutions, highlighting ARIMA's limitations for long-term forecasting of cerebral physiologic signals with lower resolution data commonly recorded in patient records.

Conclusions: This study highlights the significant influence of temporal resolution and data partitioning methods on the predictive performance of ARIMA models for cerebral physiological signals. While ARIMA performs well at high temporal resolutions, its accuracy declines for raw physiological signals as resolution decreases. The choice of cross-validation method also impacts forecasting performance. The findings underscore the need for hybrid modeling approaches that integrate ARIMA with machine learning techniques to improve predictive accuracy, particularly for complex cerebral physiological signals.

Background: Albumin is the most abundant protein in the human circulation and has many important functions. Recent studies have shown that albumin is a free radical scavenger and can be oxidized to single (HNA-1) or double (HNA-2) oxidized albumin. Oxidized albumin is a predictor for mortality in liver disease, but little is known about oxidized albumin in other diseases. This study aims to explore oxidized albumin levels in critically ill Covid-19 patients and its association with hospital mortality.

Methods: In this single-center, retrospective cohort study we included Covid-19 patients (n = 164) treated on the ICU of Karolinska University Hospital between April 2020 and May 2021. Patient data were gathered from the electronic patient records. Oxidized albumin fractions were measured in plasma samples collected within the first 48 h of ICU admission and compared with healthy volunteers (n = 10). To assess the clinical relevance of oxidized albumin, descriptive statistics were performed after dividing the study group in three tertiles based on HNA-1 levels and two groups based on the presence and absence of HNA-2. A post hoc multivariable linear regression analysis was performed to assess the correlation between oxidized albumin fraction and creatinine levels.

Results: HNA-1 levels were 5.1 percent point higher (p = 0.01) in Covid-19 patients than in healthy controls. There was no significant difference in HNA-2 levels. Hospital mortality, length of ICU stay and duration of mechanical ventilation did not differ significantly between patients with high levels of oxidized albumin and patients with low levels of oxidized albumin. Creatinine levels and sequential organ failure assessment (SOFA) scores were higher in patients with more oxidized albumin. Multivariable linear regression showed a weak but clinically relevant correlation between the fraction of oxidized albumin and creatinine, when corrected for age and chronic kidney disease before ICU admission (R² 0.31, p < 0.001).

Conclusion: Fractions of HNA-1 were higher in Covid-19 patients compared to healthy controls. In critically ill Covid-19 patients elevated levels of oxidized albumin were not associated with higher hospital mortality. Higher HNA-1 levels were associated with higher creatinine levels and higher SOFA scores. These findings contribute to increased knowledge about oxidized albumin in critically ill Covid-19 patients and can inspire future research.

Background: Transpulmonary pressure, calculated as the difference between airway pressure (Paw) and esophageal pressure (Pes), is an important monitoring parameter during assisted mechanical ventilation, provided Pes is measured via a correctly placed and filled esophageal pressure probe. The reference method to verify Pes accuracy in spontaneously breathing patients requires calculating the ratio of changes in Pes and Paw (ΔPes/ΔPaw) during an inspiratory effort against an occluded airway. We hypothesized that the P0.1 maneuver, a brief and repeatable test, could provide an alternative means to assess ΔPes/ΔPaw during assisted mechanical ventilation.

Methods: We performed an exploratory secondary analysis of data from a multicenter prospective observational study (ICEBERG study; NCT05203536). In 35 patients receiving assisted mechanical ventilation, ΔPes/ΔPaw obtained during P0.1 maneuvers (Ratio_P0.1, experimental method) was compared with ΔPes/ΔPaw from prolonged expiratory occlusion maneuvers (Ratio_occ, reference method) using linear regression and Bland-Altman analysis.

Results: Among 25 patients with 65 evaluable measurements, Ratio_P0.1 showed a moderate correlation (R²:0.647, p < 0.0001) with Ratio_occ. Bland-Altman analysis demonstrated minimal bias and acceptable agreement between methods. Using the occlusion maneuver as reference, Ratio_P0.1 identified incorrect Pes measurement with a sensitivity of 93% and a specificity for identifying correct Pes measurement of 71%. Results were consistent across patient subgroups.

Conclusions: Our exploratory analysis suggests that the P0.1 maneuver may support semi-continuous screening of esophageal pressure signal validity during assisted ventilation. While abnormal P0.1 values should prompt confirmatory occlusion testing, values within the expected range may help rule out major measurement errors. These findings provide a rationale for prospective validation studies including different ventilator types.

Trial registration: clinicaltrials.gov, NCT05203536. Registered 24. January 2022-Retrospectively registered, https://classic.

Clinicaltrials: gov/ct2/show/NCT05203536.

Background: In patients with blunt thoracic injury requiring mechanical ventilation lateral positioning is routinely performed. Whether it modifies ventilation distribution and aeration is unclear.

Study design and methods: Patients receiving pressure support ventilation (PSV) were positioned 30 degrees on each side for 30 min. Electrical impedance tomography (EIT) was used to quantify the percentage of right and left ventilation. Secondary outcomes included right and left tidal volume and the modified lung ultrasound score. At baseline, patients were categorized according to ventilation distribution: symmetrical (right lung receiving 50-55% of total ventilation) or asymmetrical.

Results: Twenty-four patients were included (mean age 51 ± 20 years, 79% male) under median PSV 5 cmH₂O [25-75% IQR: 5-8] and PEEP 8 [5-8] cmH₂O. Trauma mechanisms included motor vehicle collision (50%) and fall (29%); 54% had bilateral rib fractures and 8% a flail chest. The duration of ventilation and ICU stay were 9 [5-19] and 13 [8-21] days, respectively. Regional right-lung ventilation increased slightly when the lung was dependent [53% (44-58%)], decreased when non-dependent [47% (44-53%)], compared to supine [50% (45-54%)] (p = 0.022). These effects were observed in patients with symmetrical baseline ventilation (n = 8, p = 0.011), but not in those with asymmetrical ventilation (n = 16, p = 0.391), nor in patients with low respiratory system compliance (< 50 ml/cmH₂O, n = 9, p = 0.539). In patients with symmetrical distribution, the right-lung and right-basal ultrasound score increased when dependent (p < 0.05), whereas no changes were observed in the left lung. There were no differences in respiratory mechanics or global ventilation from the beginning to the end of the session once patients were returned to supine.

Conclusion: In blunt thoracic injury, lateral positioning during PSV is associated with a modest increase in regional ventilation of the dependent lung, but this effect is limited to patients with symmetrical ventilation distribution and normal compliance. In others, longer duration or higher degree of lateralization may be required.

Introduction: Small animal models are indispensable in cardiovascular research. This scoping review aims to provide an overview of contemporary rat models for extracorporeal life support (ECLS) after global ischaemia.

Material and methods: A systematic search was conducted in PubMed, Web of Science and Embase to identify studies involving rat models of global ischaemia followed by ECLS from January 2000 to December 2024. Title and abstracts were screened by two independent reviewers, and the remaining full text was included in predefined data extraction forms.

Results: A total of 79 studies met the inclusion criteria. Male Sprague Dawley rats were predominantly used (82%), with limited reporting on animal age and inconsistent use of analgesia. The majority of studies employed ECLS configurations with roller pumps (71%), custom-made oxygenators (41%), venous drainage via the jugular vein (96%) and arterial inflow via the femoral (53%) or caudal (35%) artery. Three distinct clinical scenarios were identified: extracorporeal cardiopulmonary resuscitation (41%), emergency preservation and resuscitation (13%), and deep hypothermic circulatory arrest (47%). Substantial methodological heterogeneity was observed across models, particularly in ischaemia induction, ECLS protocols, outcome measures, and reporting standards.

Conclusion: Rat models are increasingly used in ECLS research and offer valuable opportunities for investigating pathophysiological mechanisms and advantages for translational studies. To utilize their full potential, improved standardization and adherence to existing guidelines are needed to enhance their reproducibility and clinical relevance.