Sub-phenotyping of acute respiratory distress syndrome (ARDS) could be useful for evaluating the severity of ARDS or predicting its responsiveness to given therapeutic strategies, but no studies have yet investigated the heterogeneity of patients with severe ARDS requiring veno-venous extracorporeal membrane oxygenation (V-V ECMO). We conducted this retrospective multicenter observational study in adult patients with severe ARDS treated by V-V ECMO. We performed latent class analysis (LCA) for identifying sub-phenotypes of severe ARDS based on the radiological and clinical findings at the start of ECMO support. Multivariate Cox regression analysis was conducted to investigate the differences in mortality and association between the PEEP setting of ≥ 10 cmH2O and mortality by the sub-phenotypes. We identified three sub-phenotypes from analysis of the data of a total of 544 patients with severe ARDS treated by V-V ECMO, as follows: Dry type (n = 185; 34%); Wet type (n = 169; 31%); and Fibrotic type (n = 190; 35%). The 90-days in-hospital mortality risk was higher in the patients with the Fibrotic type than in those with the Dry type (adjusted hazard ratio [95% confidence interval] 1.75 [1.10–2.79], p = 0.019) or the Wet type (1.50 [1.02–2.23], p = 0.042). The PEEP setting of ≥ 10 cmH2O during the first 3 days of ECMO decreased the 90-days in-hospital mortality risk only in patients with the Wet type, and not in those with the Dry or Fibrotic type. A significant interaction effect was observed between the Wet type and the PEEP setting of ≥ 10 cmH2O in relation to the 90-day in-hospital mortality (pinteraction = 0.036). The three sub-phenotypes showed different mortality rates and different relationships between higher PEEP settings in the early phase of V-V ECMO and patient outcomes. Our data suggest that we may need to change our management approach to patients with severe ARDS during V-V ECMO according to their clinical sub-phenotype.
{"title":"Identification of novel sub-phenotypes of severe ARDS requiring ECMO using latent class analysis","authors":"Mitsuaki Nishikimi, Shinichiro Ohshimo, Giacomo Bellani, Wataru Fukumoto, Tatsuhiko Anzai, Keibun Liu, Junki Ishii, Michihito Kyo, Kazuo Awai, Kunihiko Takahashi, Nobuaki Shime","doi":"10.1186/s13054-024-05143-3","DOIUrl":"https://doi.org/10.1186/s13054-024-05143-3","url":null,"abstract":"Sub-phenotyping of acute respiratory distress syndrome (ARDS) could be useful for evaluating the severity of ARDS or predicting its responsiveness to given therapeutic strategies, but no studies have yet investigated the heterogeneity of patients with severe ARDS requiring veno-venous extracorporeal membrane oxygenation (V-V ECMO). We conducted this retrospective multicenter observational study in adult patients with severe ARDS treated by V-V ECMO. We performed latent class analysis (LCA) for identifying sub-phenotypes of severe ARDS based on the radiological and clinical findings at the start of ECMO support. Multivariate Cox regression analysis was conducted to investigate the differences in mortality and association between the PEEP setting of ≥ 10 cmH2O and mortality by the sub-phenotypes. We identified three sub-phenotypes from analysis of the data of a total of 544 patients with severe ARDS treated by V-V ECMO, as follows: Dry type (n = 185; 34%); Wet type (n = 169; 31%); and Fibrotic type (n = 190; 35%). The 90-days in-hospital mortality risk was higher in the patients with the Fibrotic type than in those with the Dry type (adjusted hazard ratio [95% confidence interval] 1.75 [1.10–2.79], p = 0.019) or the Wet type (1.50 [1.02–2.23], p = 0.042). The PEEP setting of ≥ 10 cmH2O during the first 3 days of ECMO decreased the 90-days in-hospital mortality risk only in patients with the Wet type, and not in those with the Dry or Fibrotic type. A significant interaction effect was observed between the Wet type and the PEEP setting of ≥ 10 cmH2O in relation to the 90-day in-hospital mortality (pinteraction = 0.036). The three sub-phenotypes showed different mortality rates and different relationships between higher PEEP settings in the early phase of V-V ECMO and patient outcomes. Our data suggest that we may need to change our management approach to patients with severe ARDS during V-V ECMO according to their clinical sub-phenotype.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"211 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-22DOI: 10.1186/s13054-024-05124-6
Bianca Morosanu, Cosmin Balan, Cristian Boros, Federico Dazzi, Adrian Wong, Francesco Corradi, Serban-Ion Bubenek-Turconi
Fluid administration has traditionally focused on preload responsiveness (PR). However, preventing fluid intolerance, particularly due to systemic venous congestion (VC), is equally important. This study evaluated the incidence and predictability of VC following a 7 ml/kg crystalloid infusion in fluid-tolerant preload-responders and its association with adverse outcomes. This single-center, prospective, observational study (May 2023–July 2024) included 40 consecutive patients who were mechanically ventilated within 6 h of intensive care unit (ICU) admission after elective open-heart surgery and had acute circulatory failure. Patients were eligible if they were both fluid-tolerant and preload-responsive. PR was defined as a ≥ 12% increase in left-ventricular outflow tract velocity time integral (LVOT-VTI) 1 min after a passive leg raising (PLR) test. VC was defined by a portal vein pulsatility index (PVPI) ≥ 50%. Patients received a 7 ml/kg Ringer’s Lactate infusion over 10 min. The primary outcome was the incidence of VC 2 min post-infusion (early-VC). Secondary outcomes included VC at 20 min, the incidence of acute kidney injury (AKI) and severe AKI at 7 days, and ICU length of stay (LOS). 45% of patients developed early-VC, with VC persisting in only 5% at 20 min. One-third of patients developed AKI, with 17.5% progressing to severe AKI. The median ICU LOS was 4 days. Patients with early-VC had significantly higher central venous pressure, lower mean perfusion pressure, worse baseline right ventricular function, and a higher incidence of severe AKI. While LVOT-VTI returned to baseline by 20 min in both groups, PVPI remained elevated in early-VC patients (p < 0.001). The LVOT-VTI versus PVPI regression line showed similar slopes (p = 0.755) but different intercepts (p < 0.001), indicating that, despite fluid tolerance and PR at baseline, early-VC patients had reduced right ventricular diastolic reserve (RVDR). Post-PLR PVPI predicted early-VC with an area under the curve of 0.998, using a threshold of 44.3% (p < 0.001). Post-PLR PVPI effectively predicts fluid-induced early-VC in fluid-tolerant preload-responders, identifying those with poor RVDR. Its use can guide fluid management in cardiac surgery patients, helping to prevent unnecessary fluid administration and associated complications. Trial Registration: NCT06440772. Registered 30 May 2024. Retrospectively registered.
{"title":"Incidence, predictability, and outcomes of systemic venous congestion following a fluid challenge in initially fluid-tolerant preload-responders after cardiac surgery: a pilot trial","authors":"Bianca Morosanu, Cosmin Balan, Cristian Boros, Federico Dazzi, Adrian Wong, Francesco Corradi, Serban-Ion Bubenek-Turconi","doi":"10.1186/s13054-024-05124-6","DOIUrl":"https://doi.org/10.1186/s13054-024-05124-6","url":null,"abstract":"Fluid administration has traditionally focused on preload responsiveness (PR). However, preventing fluid intolerance, particularly due to systemic venous congestion (VC), is equally important. This study evaluated the incidence and predictability of VC following a 7 ml/kg crystalloid infusion in fluid-tolerant preload-responders and its association with adverse outcomes. This single-center, prospective, observational study (May 2023–July 2024) included 40 consecutive patients who were mechanically ventilated within 6 h of intensive care unit (ICU) admission after elective open-heart surgery and had acute circulatory failure. Patients were eligible if they were both fluid-tolerant and preload-responsive. PR was defined as a ≥ 12% increase in left-ventricular outflow tract velocity time integral (LVOT-VTI) 1 min after a passive leg raising (PLR) test. VC was defined by a portal vein pulsatility index (PVPI) ≥ 50%. Patients received a 7 ml/kg Ringer’s Lactate infusion over 10 min. The primary outcome was the incidence of VC 2 min post-infusion (early-VC). Secondary outcomes included VC at 20 min, the incidence of acute kidney injury (AKI) and severe AKI at 7 days, and ICU length of stay (LOS). 45% of patients developed early-VC, with VC persisting in only 5% at 20 min. One-third of patients developed AKI, with 17.5% progressing to severe AKI. The median ICU LOS was 4 days. Patients with early-VC had significantly higher central venous pressure, lower mean perfusion pressure, worse baseline right ventricular function, and a higher incidence of severe AKI. While LVOT-VTI returned to baseline by 20 min in both groups, PVPI remained elevated in early-VC patients (p < 0.001). The LVOT-VTI versus PVPI regression line showed similar slopes (p = 0.755) but different intercepts (p < 0.001), indicating that, despite fluid tolerance and PR at baseline, early-VC patients had reduced right ventricular diastolic reserve (RVDR). Post-PLR PVPI predicted early-VC with an area under the curve of 0.998, using a threshold of 44.3% (p < 0.001). Post-PLR PVPI effectively predicts fluid-induced early-VC in fluid-tolerant preload-responders, identifying those with poor RVDR. Its use can guide fluid management in cardiac surgery patients, helping to prevent unnecessary fluid administration and associated complications. Trial Registration: NCT06440772. Registered 30 May 2024. Retrospectively registered.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"222 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-22DOI: 10.1186/s13054-024-05131-7
Ayman El-Menyar, Mashhood Naduvilekandy
<p>The cardiopulmonary resuscitation (CPR) technique and its outcome remains a debate. In response to Zhao et al.'s [1] regarding the inclusion of duplicated studies in the meta-analysis [2], we have conducted a thorough review of the two studies published by Ong et al. (2012) and Casner et al. (2005). After that, we removed these two studies, along with an additional data point from Halperin et al. (1993), which exhibited high variance and did not meet the variance thresholds set for our updated analysis, and then we performed a revised meta-analysis to maintain consistency. Despite these changes, the results remained consistent, with an (Odds Ratio (OR) of 1.11; 95% CI 0.99–1.22) (Fig. 1). Thus, our original umbrella review findings [2] and Zhao et al.'s analysis showed that mechanical CPR was not superior to manual CPR in achieving the return of spontaneous circulation (ROSC).</p><figure><figcaption><b data-test="figure-caption-text">Fig. 1</b></figcaption><picture><source srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13054-024-05131-7/MediaObjects/13054_2024_5131_Fig1_HTML.png?as=webp" type="image/webp"/><img alt="figure 1" aria-describedby="Fig1" height="525" loading="lazy" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13054-024-05131-7/MediaObjects/13054_2024_5131_Fig1_HTML.png" width="685"/></picture><p>Revised Forest plot of pooled odds ratio for ROSC of studies included in the Umbrella review after removing the duplicate and a study with a high variance</p><span>Full size image</span><svg aria-hidden="true" focusable="false" height="16" role="img" width="16"><use xlink:href="#icon-eds-i-chevron-right-small" xmlns:xlink="http://www.w3.org/1999/xlink"></use></svg></figure><p>We respectfully disagree with Zhao et al. second point regarding the inclusion of Axelson et al. (2013) and Jennings et al. (2012) in the meta-analysis. A few relevant data required for our analysis were obtained from the already published systematic review (SR) by Sheraton et al. (2021) [3]. The ROSC-related ORs were extracted from the second graph of the Sheraton et al. meta-analysis [3]. It is also worth noting that Zhao et al. [1] included a study published by Hallstrom et al. (2006) [4], even though this study did not explicitly mention ROSC as an outcome in the original work.</p><p>We agree that data derived solely from abstracts can affect the robustness of outcomes; therefore, we intended to gather and synthesize as much data as possible from the published SRs and not from individual studies or abstracts for the umbrella review [2]. However, for the umbrella meta-analysis, data from 3 abstracts (Lairet et al. (2005), Paradis et al. (2009), and Morozov et al. (2012)) were used. The ORs from these abstracts were extracted from a meta-analysis published by Bonnes et al. (2016) and their illustrations [5]. Thus, in this letter, we recalculated the ORs after removing data gathered from abstracts or did
开放获取本文采用知识共享署名 4.0 国际许可协议进行许可，该协议允许以任何媒介或格式使用、共享、改编、分发和复制本文，只要您适当注明原作者和来源，提供知识共享许可协议的链接，并说明是否进行了修改。本文中的图片或其他第三方材料均包含在文章的知识共享许可协议中，除非在材料的署名栏中另有说明。如果材料未包含在文章的知识共享许可协议中，且您打算使用的材料不符合法律规定或超出许可使用范围，您需要直接从版权所有者处获得许可。要查看该许可的副本，请访问 http://creativecommons.org/licenses/by/4.0/.Reprints and permissionsCite this articleEl-Menyar, A., Naduvilekandy, M. An update on the mechanical versus manual cardiopulmonary resuscitation in cardiac arrest patients.https://doi.org/10.1186/s13054-024-05131-7Download citationReceived：09 October 2024Accepted：11 October 2024Published: 22 October 2024DOI: https://doi.org/10.1186/s13054-024-05131-7Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative.
{"title":"An update on the mechanical versus manual cardiopulmonary resuscitation in cardiac arrest patients","authors":"Ayman El-Menyar, Mashhood Naduvilekandy","doi":"10.1186/s13054-024-05131-7","DOIUrl":"https://doi.org/10.1186/s13054-024-05131-7","url":null,"abstract":"<p>The cardiopulmonary resuscitation (CPR) technique and its outcome remains a debate. In response to Zhao et al.'s [1] regarding the inclusion of duplicated studies in the meta-analysis [2], we have conducted a thorough review of the two studies published by Ong et al. (2012) and Casner et al. (2005). After that, we removed these two studies, along with an additional data point from Halperin et al. (1993), which exhibited high variance and did not meet the variance thresholds set for our updated analysis, and then we performed a revised meta-analysis to maintain consistency. Despite these changes, the results remained consistent, with an (Odds Ratio (OR) of 1.11; 95% CI 0.99–1.22) (Fig. 1). Thus, our original umbrella review findings [2] and Zhao et al.'s analysis showed that mechanical CPR was not superior to manual CPR in achieving the return of spontaneous circulation (ROSC).</p><figure><figcaption><b data-test=\"figure-caption-text\">Fig. 1</b></figcaption><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13054-024-05131-7/MediaObjects/13054_2024_5131_Fig1_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure 1\" aria-describedby=\"Fig1\" height=\"525\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13054-024-05131-7/MediaObjects/13054_2024_5131_Fig1_HTML.png\" width=\"685\"/></picture><p>Revised Forest plot of pooled odds ratio for ROSC of studies included in the Umbrella review after removing the duplicate and a study with a high variance</p><span>Full size image</span><svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-chevron-right-small\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></figure><p>We respectfully disagree with Zhao et al. second point regarding the inclusion of Axelson et al. (2013) and Jennings et al. (2012) in the meta-analysis. A few relevant data required for our analysis were obtained from the already published systematic review (SR) by Sheraton et al. (2021) [3]. The ROSC-related ORs were extracted from the second graph of the Sheraton et al. meta-analysis [3]. It is also worth noting that Zhao et al. [1] included a study published by Hallstrom et al. (2006) [4], even though this study did not explicitly mention ROSC as an outcome in the original work.</p><p>We agree that data derived solely from abstracts can affect the robustness of outcomes; therefore, we intended to gather and synthesize as much data as possible from the published SRs and not from individual studies or abstracts for the umbrella review [2]. However, for the umbrella meta-analysis, data from 3 abstracts (Lairet et al. (2005), Paradis et al. (2009), and Morozov et al. (2012)) were used. The ORs from these abstracts were extracted from a meta-analysis published by Bonnes et al. (2016) and their illustrations [5]. Thus, in this letter, we recalculated the ORs after removing data gathered from abstracts or did","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"44 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-22DOI: 10.1186/s13054-024-05137-1
Han Chen, Takeshi Yoshida, Jian-Xin Zhou
<p><b>To the Editor</b></p><p>Electrical impedance tomography (EIT) is increasingly utilized for tailoring positive end-expiratory pressure (PEEP). By non-invasively assessing lung collapse and over-distention [1], EIT helps adjust PEEP to minimize both conditions, assuming they are equally harmful. The EIT-guided PEEP selection approach may potentially provide more lung protection by reducing mechanical power [2].</p><p>Although the balance between over-distension and collapse may help individualize PEEP titration, the requirement for specialized EIT equipment limits its widespread application. Furthermore, EIT focuses on morphology without considering PEEP's impact on hemodynamics and ventilation-perfusion matching. Alternatively, PEEP can be titrated by calculating intrapulmonary shunt (Qs/Qt) and dead space (Vd/Vt) using blood gases [3]. High alveolar pressure can cause both lung over-distension (high stress and strain) and pulmonary capillary collapse and subsequently impaired CO<sub>2</sub> elimination (namely functional over-distension). However, whether the calculated Vd/Vt and Qs/Qt are consistent with EIT-derived over-distension and collapse is unclear. In this pilot study, we attempted to compare these PEEP selection approaches.</p><p>The experiment protocol was approved by the Animal Care Committee of Fujian Provincial Hospital. The animals were treated in compliance with the hospital's guidelines for the care and utilization of laboratory animals.</p><h3>Preparation and measurements</h3><p>Eight male Bama miniatured pigs (weight 40.1 to 58.0 kg) were anesthetized with 10 mg·kg<sup>–1</sup>·h<sup>–1</sup> pentobarbital. Rocuronium bromide boluses of 0.5 mg·kg<sup>–1</sup> were administered as needed to suppress spontaneous breathing. After tracheotomy, mechanical ventilation was initiated. A catheter in the right carotid artery enabled blood pressure monitoring and gas sampling. A Swan-Ganz catheter, inserted via the internal jugular vein, facilitated mixed venous blood sampling and hemodynamic measurements. Mixed expired CO<sub>2</sub> (PeCO<sub>2</sub>) was measured via a mainstream PeCO<sub>2</sub> module. Vital signs and cardiac output (via thermodilution) were monitored. Collapse and over-distension were determined using EIT (PulmoVista 500, Dräger, Germany) at the 4th–5th intercostal space, with thresholds previously reported [1].</p><h3>Experiment protocol</h3><p>Lung injury was induced using a 'two-hits' model: surfactant depletion and injurious ventilation [4]. Saline lung lavage (30 ml·kg-1) was repeated until PaO<sub>2</sub>/FiO<sub>2</sub> < 100 mmHg for 10 min at PEEP 5 cmH<sub>2</sub>O, followed by injurious ventilation for 60 min, with driving pressure/PEEP adjusted every 15 min [4].</p><p>After lung recruitment, a decremental PEEP trial (20 to 4 cmH<sub>2</sub>O, 2 cmH<sub>2</sub>O steps) was conducted. Static compliance, cardiac output, and blood gases were measured at each PEEP level. EIT data were continuously re
致编辑电阻抗断层扫描（EIT）越来越多地被用于调整呼气末正压（PEEP）。通过无创评估肺塌陷和过度滞留[1]，EIT 可帮助调整 PEEP 以尽量减少这两种情况（假设它们同样有害）。EIT 指导下的 PEEP 选择方法可能会通过减少机械力来提供更多的肺保护[2]。虽然过度张力和塌陷之间的平衡可能有助于个性化 PEEP 滴定，但对专业 EIT 设备的要求限制了其广泛应用。此外，EIT 只关注形态学，而不考虑 PEEP 对血液动力学和通气-灌注匹配的影响。另外，PEEP 也可以通过使用血气计算肺内分流（Qs/Qt）和死腔（Vd/Vt）来进行调节[3]。高肺泡压既可导致肺过度张力（高应力和应变），也可导致肺毛细血管塌陷，进而影响二氧化碳排出（即功能性过度张力）。然而，计算出的 Vd/Vt 和 Qs/Qt 是否与 EIT 导出的过度张力和塌陷一致尚不清楚。在这项试验性研究中，我们尝试比较这些 PEEP 选择方法。八头雄性巴马小型猪（体重 40.1 至 58.0 千克）用 10 毫克-千克-1-小时-1 戊巴比妥麻醉。根据需要注射 0.5 mg-kg-1 的罗库溴铵以抑制自主呼吸。气管切开后，开始机械通气。右颈动脉导管用于血压监测和气体采样。通过颈内静脉插入的 Swan-Ganz 导管有助于混合静脉血采样和血液动力学测量。混合呼出二氧化碳（PeCO2）通过主流 PeCO2 模块进行测量。对生命体征和心输出量（通过热稀释）进行监测。使用 EIT（PulmoVista 500，德国 Dräger）在第 4-5 肋间测定塌陷和过度张力，阈值先前已有报道[1]。实验方案使用 "两击 "模型诱导肺损伤：表面活性物质耗竭和损伤性通气[4]。盐水洗肺（30 ml-kg-1）重复进行，直到 PaO2/FiO2 < 100 mmHg 为止，持续 10 分钟，PEEP 为 5 cmH2O，然后进行 60 分钟的损伤性通气，每 15 分钟调整一次驱动压力/PEEP[4]。在每个 PEEP 水平测量静态顺应性、心输出量和血气。连续记录 EIT 数据以进行离线分析。实验结束后，对猪实施戊巴比妥过量安乐死。Qs/Qt 和 Vd/Vt 采用既定公式计算 (5)。最佳 "PEEP 通过三种方法确定：Vd/Vt 和 Qs/Qt 的最小和、最大顺应性以及 EIT 测量的过张和塌陷的最小和。当 PEEP 下降时，塌陷度和 Qs/Qt 同步上升。PaO2 与 PEEP 的变化呈非线性关系，与塌陷的相关性不强（图 1A）。随着 PEEP 的降低，过度张力减少，而 Vd/Vt 增加（图 1B）。肺顺应性在 PEEP 为 16 cmH2O 时达到峰值，而在 PEEP 为 18 cmH2O 时，塌陷和过度张力之和最小（图 1C）。血压和心输出量随着 PEEP 的降低而增加（图 1D）。就个体而言，三种方法的 "最佳 "PEEP 值各不相同。EIT 引导法和基于血气分析的 Vd/Vt + Qs/Qt 法显示，所有动物的 PEEP 值都存在差异。然而，当将 EIT 引导法与最佳顺应性法进行比较时，有两只动物的 PEEP 值相同，而其他动物的 PEEP 值仍存在差异（图 1E）。图 1 面板 A：显示肺内分流（Qs/Qt）、PaO2 和塌陷（CL）对呼气末正压（PEEP）下降的响应变化。肺内分流（Qs/Qt）和塌陷（CL）显示在左侧 y 轴上，而 PaO2 显示在右侧 y 轴上。趋势表明，Qs/Qt 和 CL 均随 PEEP 的减小而增加，Qs/Qt 和 CL 之间的趋势相关性良好。PaO2 显示出双相反应，最初上升，随后下降。B 组：显示动脉 CO2 分压（PaCO2）、混合呼出 CO2 分压（PeCO2）、死腔（Vd/Vt）和过度张力（OD）对 PEEP 下降的响应变化。Vd/Vt 和 OD 显示在左侧 y 轴上，而 PaCO2 和 PeCO2 显示在右侧 y 轴上。
{"title":"Comparison of electrical impedance tomography, blood gas analysis, and respiratory mechanics for positive end-expiratory pressure titration","authors":"Han Chen, Takeshi Yoshida, Jian-Xin Zhou","doi":"10.1186/s13054-024-05137-1","DOIUrl":"https://doi.org/10.1186/s13054-024-05137-1","url":null,"abstract":"<p><b>To the Editor</b></p><p>Electrical impedance tomography (EIT) is increasingly utilized for tailoring positive end-expiratory pressure (PEEP). By non-invasively assessing lung collapse and over-distention [1], EIT helps adjust PEEP to minimize both conditions, assuming they are equally harmful. The EIT-guided PEEP selection approach may potentially provide more lung protection by reducing mechanical power [2].</p><p>Although the balance between over-distension and collapse may help individualize PEEP titration, the requirement for specialized EIT equipment limits its widespread application. Furthermore, EIT focuses on morphology without considering PEEP's impact on hemodynamics and ventilation-perfusion matching. Alternatively, PEEP can be titrated by calculating intrapulmonary shunt (Qs/Qt) and dead space (Vd/Vt) using blood gases [3]. High alveolar pressure can cause both lung over-distension (high stress and strain) and pulmonary capillary collapse and subsequently impaired CO<sub>2</sub> elimination (namely functional over-distension). However, whether the calculated Vd/Vt and Qs/Qt are consistent with EIT-derived over-distension and collapse is unclear. In this pilot study, we attempted to compare these PEEP selection approaches.</p><p>The experiment protocol was approved by the Animal Care Committee of Fujian Provincial Hospital. The animals were treated in compliance with the hospital's guidelines for the care and utilization of laboratory animals.</p><h3>Preparation and measurements</h3><p>Eight male Bama miniatured pigs (weight 40.1 to 58.0 kg) were anesthetized with 10 mg·kg<sup>–1</sup>·h<sup>–1</sup> pentobarbital. Rocuronium bromide boluses of 0.5 mg·kg<sup>–1</sup> were administered as needed to suppress spontaneous breathing. After tracheotomy, mechanical ventilation was initiated. A catheter in the right carotid artery enabled blood pressure monitoring and gas sampling. A Swan-Ganz catheter, inserted via the internal jugular vein, facilitated mixed venous blood sampling and hemodynamic measurements. Mixed expired CO<sub>2</sub> (PeCO<sub>2</sub>) was measured via a mainstream PeCO<sub>2</sub> module. Vital signs and cardiac output (via thermodilution) were monitored. Collapse and over-distension were determined using EIT (PulmoVista 500, Dräger, Germany) at the 4th–5th intercostal space, with thresholds previously reported [1].</p><h3>Experiment protocol</h3><p>Lung injury was induced using a 'two-hits' model: surfactant depletion and injurious ventilation [4]. Saline lung lavage (30 ml·kg-1) was repeated until PaO<sub>2</sub>/FiO<sub>2</sub> < 100 mmHg for 10 min at PEEP 5 cmH<sub>2</sub>O, followed by injurious ventilation for 60 min, with driving pressure/PEEP adjusted every 15 min [4].</p><p>After lung recruitment, a decremental PEEP trial (20 to 4 cmH<sub>2</sub>O, 2 cmH<sub>2</sub>O steps) was conducted. Static compliance, cardiac output, and blood gases were measured at each PEEP level. EIT data were continuously re","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"234 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-22DOI: 10.1186/s13054-024-05105-9
Stefano Romagnoli, Basil Matta, Brian E. Driver, Lisbeth Evered
<p>Awareness with recall during surgery and anesthesia occurs when the hypnotic and amnesic components of a general anesthetic fail to sustain disconnected consciousness and ablate memory. This is a rare yet significant complication that occurs in a small percentage (0.1–0.2%) of patients undergoing surgery under general anaesthesia [1]. This phenomenon involves the vivid recollection of sensory experiences during surgery, which can lead to posttraumatic stress disorders. The risk of being aware under general anaesthesia in highest in those patients who are administered muscle relaxants without sufficient hypnotics as they are unable to communicate due to paralysis. This event is frequently associated with a number of dramatic feelings (e.g., patients thinking “they were going to die,” sensations of fear and terror, feelings of being unsafe and abandoned or betrayed by doctors and nurses, and pain on being mechanically ventilated).</p><p>An unexpected number of patients suffer awareness after emergency tracheal intubation. Recent research, including a meta-analysis of randomized or nonrandomized studies (<i>n</i> = 941 patients)[2] revealed that an overall estimate of 12.3% of patients who receive a neuromuscular blocking agent for muscle relaxation before tracheal intubation and during mechanical ventilation in the emergency department (ED) might recover consciousness and encode memories of the intubation manoeuvre, mechanical ventilation, a bronchoscopy, or a combination of these and other painful procedures [2,3,4,5]. This occurrence could be underestimated due to factors like patient mortality before extubation, memory loss, or neurological deficits. This concerning incidence of conscious paralysis may result from a combination of factors that include the urgent nature of critical patient conditions, intubation before optimal hypnotic effects, anesthetic under-dosing to avoid hemodynamic collapse, and the lack of sedation-protocolized monitoring during invasive mechanical ventilation. Notably, patients’ pharmacogenomics, pharmacokinetics, and pharmacodynamics vary significantly, complicating the dosage-effect relationship of hypnotics and muscle relaxants [6] and clinical sedation assessments before intubation may not guarantee continued unconsciousness due to the complex interplay between hypnotics and painful stimuli.</p><p>While adjusting sedative dosages seems logical, it can be challenging in critically ill, paralyzed patients. Hemodynamic vital signs are often used as proxies for sedation, but they lack precision. Heart rate and blood pressure are unreliable for determining unconsciousness or the degree of sedation or anesthetic depth.</p><p>The development and the diffusion of depth-of-anesthesia monitors (DOA) has made intraoperative electroencephalography (EEG) more accessible and practical for detecting excessive light anesthesia, thus reducing the risk of intraoperative awareness. Modern DOA monitors help the physician with the com
文章PubMed Google Scholar 下载参考文献作者和工作单位意大利佛罗伦萨Stefano Romagnoli佛罗伦萨大学麻醉和重症监护科健康科学系意大利佛罗伦萨Stefano Romagnoli Azienda Ospedaliero-Universitaria Careggi医院麻醉和重症监护科、意大利佛罗伦萨斯特凡诺-罗马尼奥利英国剑桥大学Basil Matta美国加利福尼亚州尔湾市马西莫国际尔湾分部美国明尼苏达州明尼阿波利斯市亨内平县医疗中心急诊医学部肺部和重症监护分部Brian E. Driver美国明尼苏达州明尼阿波利斯市亨内平县医疗中心急诊医学部肺部和重症监护分部Driver美国纽约威尔康奈尔医学院麻醉科ALisbeth EveredSt.Vincent's Hospital, Melbourne, Fitzroy, VIC, AustraliaLisbeth EveredUniversity of Melbourne, Fitzroy, VIC, AustraliaLisbeth Evered作者Stefano Romagnoli查看作者发表的文章您也可以在PubMed Google Scholar中搜索该作者Basil Matta查看作者发表的文章您也可以在PubMed Google Scholar中搜索该作者Brian E.Driver查看作者发表的作品您也可以在PubMed Google Scholar中搜索该作者Lisbeth Evered查看作者发表的作品您也可以在PubMed Google Scholar中搜索该作者ContributionsSR构思了该手稿，编写了文本和图表的初稿，并邀请其他作者参与撰写。BM 作为神经监测专家审阅了手稿的最终版本。DBE 作为论文主题方面的专家参与了文稿的撰写。EL 作为神经监测和神经系统疾病方面的专家参与了稿件的撰写。所有作者都参与了论文的重要修改和最终审批。通讯作者：Stefano Romagnoli。利益冲突SR获得了费森尤斯、Masimo和美敦力的大会演讲资助。BM是美国加利福尼亚州欧文市Masimo国际公司的全球高级医疗总监；BED和LE声明没有利益冲突。出版商注释Springer Nature对出版地图中的管辖权主张和机构隶属关系保持中立。0 国际许可协议，该协议允许以任何媒介或格式进行任何非商业性使用、共享、分发和复制，只要您适当注明原作者和来源，提供知识共享许可协议的链接，并说明您是否修改了许可材料。根据本许可协议，您无权分享源自本文或本文部分内容的改编材料。本文中的图片或其他第三方材料均包含在文章的知识共享许可协议中，除非在材料的信用栏中另有说明。如果材料未包含在文章的知识共享许可协议中，且您打算使用的材料不符合法律规定或超出了许可使用范围，则您需要直接获得版权所有者的许可。如需查看该许可的副本，请访问 http://creativecommons.org/licenses/by-nc-nd/4.0/.Reprints and permissionsCite this articleRomagnoli, S., Matta, B., Driver, B.E. et al.https://doi.org/10.1186/s13054-024-05105-9Download citationReceived：08 September 2024Accepted：18 September 2024Published: 22 October 2024DOI: https://doi.org/10.1186/s13054-024-05105-9Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative
{"title":"A plea for enhanced monitoring of depth of sedation in patients who are intubated and ventilated","authors":"Stefano Romagnoli, Basil Matta, Brian E. Driver, Lisbeth Evered","doi":"10.1186/s13054-024-05105-9","DOIUrl":"https://doi.org/10.1186/s13054-024-05105-9","url":null,"abstract":"<p>Awareness with recall during surgery and anesthesia occurs when the hypnotic and amnesic components of a general anesthetic fail to sustain disconnected consciousness and ablate memory. This is a rare yet significant complication that occurs in a small percentage (0.1–0.2%) of patients undergoing surgery under general anaesthesia [1]. This phenomenon involves the vivid recollection of sensory experiences during surgery, which can lead to posttraumatic stress disorders. The risk of being aware under general anaesthesia in highest in those patients who are administered muscle relaxants without sufficient hypnotics as they are unable to communicate due to paralysis. This event is frequently associated with a number of dramatic feelings (e.g., patients thinking “they were going to die,” sensations of fear and terror, feelings of being unsafe and abandoned or betrayed by doctors and nurses, and pain on being mechanically ventilated).</p><p>An unexpected number of patients suffer awareness after emergency tracheal intubation. Recent research, including a meta-analysis of randomized or nonrandomized studies (<i>n</i> = 941 patients)[2] revealed that an overall estimate of 12.3% of patients who receive a neuromuscular blocking agent for muscle relaxation before tracheal intubation and during mechanical ventilation in the emergency department (ED) might recover consciousness and encode memories of the intubation manoeuvre, mechanical ventilation, a bronchoscopy, or a combination of these and other painful procedures [2,3,4,5]. This occurrence could be underestimated due to factors like patient mortality before extubation, memory loss, or neurological deficits. This concerning incidence of conscious paralysis may result from a combination of factors that include the urgent nature of critical patient conditions, intubation before optimal hypnotic effects, anesthetic under-dosing to avoid hemodynamic collapse, and the lack of sedation-protocolized monitoring during invasive mechanical ventilation. Notably, patients’ pharmacogenomics, pharmacokinetics, and pharmacodynamics vary significantly, complicating the dosage-effect relationship of hypnotics and muscle relaxants [6] and clinical sedation assessments before intubation may not guarantee continued unconsciousness due to the complex interplay between hypnotics and painful stimuli.</p><p>While adjusting sedative dosages seems logical, it can be challenging in critically ill, paralyzed patients. Hemodynamic vital signs are often used as proxies for sedation, but they lack precision. Heart rate and blood pressure are unreliable for determining unconsciousness or the degree of sedation or anesthetic depth.</p><p>The development and the diffusion of depth-of-anesthesia monitors (DOA) has made intraoperative electroencephalography (EEG) more accessible and practical for detecting excessive light anesthesia, thus reducing the risk of intraoperative awareness. Modern DOA monitors help the physician with the com","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"34 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-21DOI: 10.1186/s13054-024-05108-6
Kali A. Barrett, Fatima Sheikh, Victoria Chechulina, Hannah Chung, Peter Dodek, Laura Rosella, Kednapa Thavorn, Damon C. Scales
High-cost users (HCU) represent important targets for health policy interventions. Sepsis is a life-threatening syndrome that is associated with high morbidity, mortality, and economic costs to the healthcare system. We sought to estimate the effect of sepsis on being a subsequent HCU. Using linked health-administrative databases, we conducted a population-based, propensity score-weighted cohort study of adults who survived a hospitalization in Ontario, Canada between January 2016 and December 2017. Sepsis was identified using a validated algorithm. The primary outcome was being a persistent HCU after hospital discharge (in the top 5% or 1% of total health care spending for 90 consecutive days), and the proportion of follow-up time since discharge as a HCU. We identified 927,057 hospitalized individuals, of whom 79,065 had sepsis. Individuals who had sepsis were more likely to be a top 5% HCU for 90 consecutive days at any time after discharge compared to those without sepsis (OR 2.24; 95% confidence interval [CI] 2.04–2.46) and spent on average 42.3% of their follow up time as a top 5% HCU compared to 28.9% of time among those without sepsis (RR 1.46; 95% CI 1.45–1.48). Individuals with sepsis were more likely to be a top 1% HCU for 90 consecutive days compared to those without sepsis (10% versus 5.1%, OR 2.05 [95% CI 1.99–2.11]), and spent more time as a top 1% HCU (18.5% of time versus 10.8% of time, RR 1.68 [95% CI 1.65–1.70]). The sequelae of sepsis result in higher healthcare costs with important economic implications. After discharge, individuals who experienced sepsis are more likely to be a HCU and spend more time as a HCU compared to individuals who did not experience sepsis during hospitalization.
{"title":"High-cost users after sepsis: a population-based observational cohort study","authors":"Kali A. Barrett, Fatima Sheikh, Victoria Chechulina, Hannah Chung, Peter Dodek, Laura Rosella, Kednapa Thavorn, Damon C. Scales","doi":"10.1186/s13054-024-05108-6","DOIUrl":"https://doi.org/10.1186/s13054-024-05108-6","url":null,"abstract":"High-cost users (HCU) represent important targets for health policy interventions. Sepsis is a life-threatening syndrome that is associated with high morbidity, mortality, and economic costs to the healthcare system. We sought to estimate the effect of sepsis on being a subsequent HCU. Using linked health-administrative databases, we conducted a population-based, propensity score-weighted cohort study of adults who survived a hospitalization in Ontario, Canada between January 2016 and December 2017. Sepsis was identified using a validated algorithm. The primary outcome was being a persistent HCU after hospital discharge (in the top 5% or 1% of total health care spending for 90 consecutive days), and the proportion of follow-up time since discharge as a HCU. We identified 927,057 hospitalized individuals, of whom 79,065 had sepsis. Individuals who had sepsis were more likely to be a top 5% HCU for 90 consecutive days at any time after discharge compared to those without sepsis (OR 2.24; 95% confidence interval [CI] 2.04–2.46) and spent on average 42.3% of their follow up time as a top 5% HCU compared to 28.9% of time among those without sepsis (RR 1.46; 95% CI 1.45–1.48). Individuals with sepsis were more likely to be a top 1% HCU for 90 consecutive days compared to those without sepsis (10% versus 5.1%, OR 2.05 [95% CI 1.99–2.11]), and spent more time as a top 1% HCU (18.5% of time versus 10.8% of time, RR 1.68 [95% CI 1.65–1.70]). The sequelae of sepsis result in higher healthcare costs with important economic implications. After discharge, individuals who experienced sepsis are more likely to be a HCU and spend more time as a HCU compared to individuals who did not experience sepsis during hospitalization.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"84 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-18DOI: 10.1186/s13054-024-05126-4
María Marín-Cerezuela, Ruben Martín-Latorre, Juan Frasquet, Jesus Ruiz-Ramos, Sandra Garcia-Contreras, Mónica Gordón, María Jesús Broch, Álvaro Castellanos-Ortega, Paula Ramirez
<p><b>To the Editor,</b></p><p>Extracorporeal membrane oxygenation (ECMO) is increasingly being used as a rescue therapy for severe acute respiratory distress syndrome or severe circulatory failure. Nosocomial infections are common in ECMO patients; therefore, antibiotics are frequently used [1]. However, preliminary evidence suggests that ECMO support could alter antibiotic serum concentrations. Both subtherapeutic and elevated serum concentrations of commonly used antimicrobial agents have been reported [2]. New antimicrobials, especially novel β-Lactams and β-Lactam/β-Lactamase inhibitors, have been commercialized after a thorough pharmacokinetic (PK) assessment. However, new molecule PK changes have again been reported in critically ill patients, especially in those on ECMO support [3]. Circuit adsorption and sequestration are added to critical illness PK derangements, yet the specific weight of each of these factors is not clear [2, 3]. Cefiderocol is a siderophore cephalosporin active against gram-negative bacteria, including carbapenemase-producing strains, with promising positioning for difficult-to-treat infections. Scarce data has been published about its pharmacokinetics in patients with ECMO support [2, 3]. Therefore, we performed an observational and prospective study including adult critically ill patients treated with cefiderocol between January 2022 and December 2023 at a tertiary university hospital. Total plasma concentrations (Cp) at trough (C<sub>min</sub>) and at the end of the 3 h infusion (C<sub>max</sub>) were determined using UPLC-MS/MS after at least 72 h of treatment were completed. Free plasma concentrations (<i>f</i>C<sub>min</sub>, <i>f</i>C<sub>max</sub>) were corrected using the average protein binding from clinical pharmakocinetic studies [4]. The minimum inhibitory concentration (MIC) of cefiderocol on the antibiogram was determined by the microdilution technique (UMIC® Cefiderocol BMD test). The established therapeutic objective (Pk/Pd) was when Cp was at least four times above the MIC (100%<i>f</i>T > 4 × MIC). The calculation of the pharmacokinetic parameters was performed from the plasma concentrations obtained and Pmetrics version 1.5.2 software package for R was used (1) [5]. A 3-compartment model with a proportional error model for the intraindividual variability was used (2) [6]. Hyperfiltration was considered when creatinine clearance (ClCr) exceeded 130 ml/min. Clinical response was defined as the resolution of the signs and symptoms present at the time of the infection. The study protocol was approved by the local Ethics Committee, and written informed consent was obtained from the patient or their legal representatives, and. A Student’s t-test or Mann–Whitney test was used to compare quantitative variables and Pearson’s chi-square or Fisher’s exact test for qualitative variables according to normality, using STATA v.14.2. Statistical significance was considered if <i>p</i> ≤ 0.05.</p><p>Ten caucasi
在我们的研究人群中，Vd、CL，尤其是半衰期存在重要的差异，这表明我们的病人样本存在异质性，并且存在影响头孢羟氨苄 PK 的多种因素。显然，ECMO 治疗并没有导致头孢羟氨苄的任何特殊药代动力学行为。以前在重症患者中进行的头孢羟氨苄血清浓度研究显示了不同的结果。有两项研究（分别为 50%和 23%的患者）描述了因 fCmin 值低而导致的 fT% > MIC 值不达标的情况，在后一项研究中，这与鲍曼不动杆菌感染的微生物学失败有关[7, 8]。然而，与这些变化相关的潜在因素并未得到研究。相反，在另外两项研究（包括 12 名感染多重耐药革兰氏阴性菌的难治患者）中，100%fT > 4 × MIC 得到了证实[9, 10]。Katsube 等人对 7 名肺炎患者进行了研究，他们在使用标准剂量的头孢羟氨苄治疗时，血浆和上皮内衬液中的 Pk/Pd 均达到了目标值 [9]。CRRT 的头孢羟氨苄剂量建议应根据流出率和是否存在残余肾功能进行调整。在两项包括 6 名患者的研究中，对这两个因素进行了评估，以确定全剂量（2 克/8 小时），实现了准确的血浆浓度，且未发现不良事件[11, 12]。在两项体内外研究中，成功评估了 ECMO 患者的头孢羟氨苄 PK，结果表明没有由于螯合或吸附造成损失[13, 14]。这些结果在一名因 COVID19 而接受 ECMO 治疗的重症患者身上得到了证实[15]。据我们所知，这是首次对有 ECMO 支持和无 ECMO 支持的危重病人进行药代动力学研究，并一并介绍。Marcus JE, Shah A, Peek GJ, MacLaren G. Nosocomial infections in adults receiving extracorporeal membrane oxygenation: a review for infectious diseases clinicians.Clin Infect Dis.2024;5:120.Google Scholar Shekar K, Abdul-Aziz MH, Cheng V, Burrows F, Buscher H, Cho YJ, et al.Am J Respir Crit Care Med.2023;207:704-20.Article PubMed Google Scholar Bakdach D, Elajez R, Bakdach AR, Awaisu A, De Pascale G, Hssain AA.新型β-内酰胺类和β-内酰胺/β-内酰胺酶抑制剂在重症成年患者中的药代动力学、药效学和剂量考虑：关注肥胖、肾清除率增加、肾替代疗法和体外膜氧合。J Clin Med.2022;11(23):6898.Article PubMed PubMed Central Google Scholar Katsube T, Echols R, Wajima T. Cefiderocol, a new siderophore cephalosporin.Clin Infect Dis.2019;69:552-8.Article Google Scholar Neely MN, van Guilder MG, Yamada WM, Schumitzky A, Jelliffe RW.使用 Pmetrics（R 的非参数和参数药物计量建模和模拟软件包）精确检测异常值和亚群。2012;34:467-76.Article PubMed PubMed Central Google Scholar Kawaguchi N, Katsube T, Echols R, Wajima T. Cefiderocol（一种肠外嗜肽头孢菌素）在肺炎、血流感染/败血症或复杂性尿路感染患者中的群体药代动力学和药代动力学/药效学分析。Antimicrob Agents Chemother.2021;65(3):e01437-e1520.Article PubMed PubMed Central Google Scholar Mernissi T, Bodeau S, Andre C, Zahr N, Mary A, Dupont H, et al.J Antimicrob Chemother.2021;76:1643-6.Article PubMed Google Scholar Gatti M、Bartoletti M、Cojutti PG、Gaibani P、Conti M、Giannella M 等。用头孢克洛治疗有记录的严重广泛耐药鲍曼不动杆菌血流感染和/或呼吸机相关肺炎重症患者的药代动力学/药效学目标实现和微生物学结果的描述性病例系列。J Glob Antimicrob Resist.2021;27:294-8.Article PubMed Google Scholar Katsube T, Nicolau DP, Rodvold KA, Wunderink RG, Echols R, Matsunaga Y, et al. Cefiderocol 在机械通气肺炎患者中的肺内药代动力学特征。J Antimicrob Chemother.2021;76(11):2902-5.Article PubMed PubMed Central Google Scholar König C, Both A, Rohde H, Kluge S, Frey OR, Röhr AC, Wichmann D. Cefiderocol in critically ill patients with multi-drug resistant pathogens: real-life data on pharmacokinetics and microbiological surveillance.抗生素（巴塞尔）。2021;10(6):649. 文章 PubMed Google Scholar Kobic E、Gill CM、Brian Mochon A、Nicolasora NP、Nicolau DP。持续静脉血液透析患者的头孢羟氨苄药代动力学。Open Forum Infect Dis.2021. https://doi.org/10.1093/ofid/ofab252.Article PubMed PubMed Central Google Scholar Gatti M, Rinaldi M, Tonetti T, Gaibani P, Siniscalchi A, Viale P, Pea F. 在接受连续静脉血液透析滤过（CVVHDF）的耐碳青霉烯鲍曼不动杆菌感染重症患者病例系列中连续输注头孢地多克的药代动力学/药效学。Int J Antimicrob Agents.2023;62(2):106852.Article PubMed Google Scholar Booke H, Friedrichson B, Draheim L, von Groote TC, Frey O, Röhr A, et al.抗生素（巴塞尔）。
{"title":"Cefiderocol pharmacokinetics in critically ill patients undergoing ECMO support","authors":"María Marín-Cerezuela, Ruben Martín-Latorre, Juan Frasquet, Jesus Ruiz-Ramos, Sandra Garcia-Contreras, Mónica Gordón, María Jesús Broch, Álvaro Castellanos-Ortega, Paula Ramirez","doi":"10.1186/s13054-024-05126-4","DOIUrl":"https://doi.org/10.1186/s13054-024-05126-4","url":null,"abstract":"<p><b>To the Editor,</b></p><p>Extracorporeal membrane oxygenation (ECMO) is increasingly being used as a rescue therapy for severe acute respiratory distress syndrome or severe circulatory failure. Nosocomial infections are common in ECMO patients; therefore, antibiotics are frequently used [1]. However, preliminary evidence suggests that ECMO support could alter antibiotic serum concentrations. Both subtherapeutic and elevated serum concentrations of commonly used antimicrobial agents have been reported [2]. New antimicrobials, especially novel β-Lactams and β-Lactam/β-Lactamase inhibitors, have been commercialized after a thorough pharmacokinetic (PK) assessment. However, new molecule PK changes have again been reported in critically ill patients, especially in those on ECMO support [3]. Circuit adsorption and sequestration are added to critical illness PK derangements, yet the specific weight of each of these factors is not clear [2, 3]. Cefiderocol is a siderophore cephalosporin active against gram-negative bacteria, including carbapenemase-producing strains, with promising positioning for difficult-to-treat infections. Scarce data has been published about its pharmacokinetics in patients with ECMO support [2, 3]. Therefore, we performed an observational and prospective study including adult critically ill patients treated with cefiderocol between January 2022 and December 2023 at a tertiary university hospital. Total plasma concentrations (Cp) at trough (C<sub>min</sub>) and at the end of the 3 h infusion (C<sub>max</sub>) were determined using UPLC-MS/MS after at least 72 h of treatment were completed. Free plasma concentrations (<i>f</i>C<sub>min</sub>, <i>f</i>C<sub>max</sub>) were corrected using the average protein binding from clinical pharmakocinetic studies [4]. The minimum inhibitory concentration (MIC) of cefiderocol on the antibiogram was determined by the microdilution technique (UMIC® Cefiderocol BMD test). The established therapeutic objective (Pk/Pd) was when Cp was at least four times above the MIC (100%<i>f</i>T > 4 × MIC). The calculation of the pharmacokinetic parameters was performed from the plasma concentrations obtained and Pmetrics version 1.5.2 software package for R was used (1) [5]. A 3-compartment model with a proportional error model for the intraindividual variability was used (2) [6]. Hyperfiltration was considered when creatinine clearance (ClCr) exceeded 130 ml/min. Clinical response was defined as the resolution of the signs and symptoms present at the time of the infection. The study protocol was approved by the local Ethics Committee, and written informed consent was obtained from the patient or their legal representatives, and. A Student’s t-test or Mann–Whitney test was used to compare quantitative variables and Pearson’s chi-square or Fisher’s exact test for qualitative variables according to normality, using STATA v.14.2. Statistical significance was considered if <i>p</i> ≤ 0.05.</p><p>Ten caucasi","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"3 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.1186/s13054-024-05130-8
Shinshu Katayama, Ken Tonai, Kie Nakamura, Misuzu Tsuji, Shinichiro Uchimasu, Atsuko Shono, Masamitsu Sanui
The dynamic regional accuracy of electrical impedance tomography has not yet been validated. We aimed to compare the regional accuracy of electrical impedance tomography with that of four-dimensional computed tomography during dynamic ventilation. This single-center, prospective, observational study conducted in a general intensive care unit included adult patients receiving mechanical ventilation from July 2021 to February 2024. The patients were mechanically ventilated passively and underwent electrical impedance tomography and four-dimensional computed tomography on the same day. Overall, 45 patients were analyzed. The correlation coefficients in regional dynamic ventilation between four-dimensional computed tomography and electrical impedance tomography in each region were 0.963, 0.963, 0.835 (ventral, central, and dorsal, respectively) in the right lung and 0.947, 0.927, 0.823 (ventral, central, and dorsal, respectively) in the left lung. The correlation coefficient was low when the regional ventilation distribution detected by the electrical impedance tomography was < 2%. After excluding nine patients with a regional ventilation distribution of < 2%, the ventral, central, and dorsal correlation coefficients were 0.963, 0.963, and 0.946 in the right lung and 0.942, 0.924, and 0.951, respectively, in the left lung. Regional ventilation using electrical impedance tomography during dynamic ventilation was highly accurate and consistent with the time phase compared to four-dimensional computed tomography. Given the high correlation between these modalities, they can contribute significantly to further studies on regional ventilation dynamics. Trial registration number ClinicalTrials.gov (No. UMIN00044386).
{"title":"Regional ventilation dynamics of electrical impedance tomography validated with four-dimensional computed tomography: single-center, prospective, observational study","authors":"Shinshu Katayama, Ken Tonai, Kie Nakamura, Misuzu Tsuji, Shinichiro Uchimasu, Atsuko Shono, Masamitsu Sanui","doi":"10.1186/s13054-024-05130-8","DOIUrl":"https://doi.org/10.1186/s13054-024-05130-8","url":null,"abstract":"The dynamic regional accuracy of electrical impedance tomography has not yet been validated. We aimed to compare the regional accuracy of electrical impedance tomography with that of four-dimensional computed tomography during dynamic ventilation. This single-center, prospective, observational study conducted in a general intensive care unit included adult patients receiving mechanical ventilation from July 2021 to February 2024. The patients were mechanically ventilated passively and underwent electrical impedance tomography and four-dimensional computed tomography on the same day. Overall, 45 patients were analyzed. The correlation coefficients in regional dynamic ventilation between four-dimensional computed tomography and electrical impedance tomography in each region were 0.963, 0.963, 0.835 (ventral, central, and dorsal, respectively) in the right lung and 0.947, 0.927, 0.823 (ventral, central, and dorsal, respectively) in the left lung. The correlation coefficient was low when the regional ventilation distribution detected by the electrical impedance tomography was < 2%. After excluding nine patients with a regional ventilation distribution of < 2%, the ventral, central, and dorsal correlation coefficients were 0.963, 0.963, and 0.946 in the right lung and 0.942, 0.924, and 0.951, respectively, in the left lung. Regional ventilation using electrical impedance tomography during dynamic ventilation was highly accurate and consistent with the time phase compared to four-dimensional computed tomography. Given the high correlation between these modalities, they can contribute significantly to further studies on regional ventilation dynamics. Trial registration number ClinicalTrials.gov (No. UMIN00044386).","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"68 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-15DOI: 10.1186/s13054-024-05119-3
Fabio Silvio Taccone, Alain Cariou, Stefano Zorzi, Hans Friberg, Janus C. Jakobsen, Per Nordberg, Chiara Robba, Jan Belohlavek, Jan Hovdenes, Matthias Haenggi, Anders Åneman, Anders Grejs, Thomas R. Keeble, Filippo Annoni, Paul J. Young, Matt P. Wise, Tobias Cronberg, Gisela Lilja, Niklas Nielsen, Josef Dankiewicz
The aim of this study was to assess whether hypothermia increased survival and improved functional outcome when compared with normothermia in out-of-hospital cardiac arrest (OHCA) patients with similar characteristics than in previous randomized studies showing benefits for hypothermia. Post hoc analysis of a pragmatic, multicenter, randomized clinical trial (TTM-2, NCT02908308). In this analysis, the subset of patients included in the trial who had similar characteristics to patients included in one previous randomized trial and randomized to hypothermia at 33 °C or normothermia (i.e. target < 37.8 °C) were considered. The primary outcome was survival at 6 months; secondary outcomes included favorable functional outcome at 6 months, defined as a modified Rankin scale of 0–3. Time-to-death and the occurrence of adverse events were also reported. From a total of 1891 included in the TTM-2 study, 600 (31.7%) were included in the analysis, 294 in the hypothermia and 306 in the normothermia group. At 6 months, 207 of the 294 patients (70.4%) in the hypothermia group and 220 of the 306 patients (71.8%) in the normothermia group had survived (relative risk with hypothermia, 0.96; 95% confidence interval [CI], 0.81 to 1.15; P = 0.71). Also, 198 of the 294 (67.3%) in the hypothermia group and 202 of the 306 (66.0%) in the normothermia group had a favorable functional outcome (relative risk with hypothermia, 1.03; 95% CI, 0.87 to 1.23; P = 0.79). There was a significant increase in the occurrence of arrythmias in the hypothermia group (62/294, 21.2%) when compared to the normothermia group (43/306, 14.1%—OR 1.49, 95% CI 1.05–2.14; p = 0.026). In this study, hypothermia at 33˚C did not improve survival or functional outcome in a subset of patients with similar cardiac arrest characteristics to patients in whom benefit from hypothermia was shown in prior studies.
{"title":"Hypothermia versus normothermia in patients with cardiac arrest and shockable rhythm: a secondary analysis of the TTM-2 study","authors":"Fabio Silvio Taccone, Alain Cariou, Stefano Zorzi, Hans Friberg, Janus C. Jakobsen, Per Nordberg, Chiara Robba, Jan Belohlavek, Jan Hovdenes, Matthias Haenggi, Anders Åneman, Anders Grejs, Thomas R. Keeble, Filippo Annoni, Paul J. Young, Matt P. Wise, Tobias Cronberg, Gisela Lilja, Niklas Nielsen, Josef Dankiewicz","doi":"10.1186/s13054-024-05119-3","DOIUrl":"https://doi.org/10.1186/s13054-024-05119-3","url":null,"abstract":"The aim of this study was to assess whether hypothermia increased survival and improved functional outcome when compared with normothermia in out-of-hospital cardiac arrest (OHCA) patients with similar characteristics than in previous randomized studies showing benefits for hypothermia. Post hoc analysis of a pragmatic, multicenter, randomized clinical trial (TTM-2, NCT02908308). In this analysis, the subset of patients included in the trial who had similar characteristics to patients included in one previous randomized trial and randomized to hypothermia at 33 °C or normothermia (i.e. target < 37.8 °C) were considered. The primary outcome was survival at 6 months; secondary outcomes included favorable functional outcome at 6 months, defined as a modified Rankin scale of 0–3. Time-to-death and the occurrence of adverse events were also reported. From a total of 1891 included in the TTM-2 study, 600 (31.7%) were included in the analysis, 294 in the hypothermia and 306 in the normothermia group. At 6 months, 207 of the 294 patients (70.4%) in the hypothermia group and 220 of the 306 patients (71.8%) in the normothermia group had survived (relative risk with hypothermia, 0.96; 95% confidence interval [CI], 0.81 to 1.15; P = 0.71). Also, 198 of the 294 (67.3%) in the hypothermia group and 202 of the 306 (66.0%) in the normothermia group had a favorable functional outcome (relative risk with hypothermia, 1.03; 95% CI, 0.87 to 1.23; P = 0.79). There was a significant increase in the occurrence of arrythmias in the hypothermia group (62/294, 21.2%) when compared to the normothermia group (43/306, 14.1%—OR 1.49, 95% CI 1.05–2.14; p = 0.026). In this study, hypothermia at 33˚C did not improve survival or functional outcome in a subset of patients with similar cardiac arrest characteristics to patients in whom benefit from hypothermia was shown in prior studies.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"40 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1186/s13054-024-05120-w
Mark C. Chappell, Christopher L. Schaich, Laurence W. Busse, Greg S. Martin, Jonathan E. Sevransky, Jeremiah K. Hinson, Ashish K. Khanna
Sepsis and septic shock remain global healthcare problems associated with high mortality rates despite best therapy efforts. Circulating biomarkers may identify those patients at risk for poor outcomes, however, current biomarkers, most prominently lactate, are non-specific and have an inconsistent impact on prognosis and/or disease management. Activation of the renin-angiotensin- system (RAS) is an early event in sepsis patients and elevated levels of circulating renin are more predictive of worse outcomes than lactate. The precursor protein Angiotensinogen is another key component of the circulating RAS; it is the only known substrate for renin and the ultimate source of the vasopressor Angiotensin II (Ang II). We postulate that lower Angiotensinogen concentrations may reflect a dysfunctional RAS characterized by high renin concentrations but attenuated Ang II generation, which is disproportionate to the high renin response and may compromise adequate support of blood pressure and tissue perfusion in septic patients. The current study compared the association between serum Angiotensinogen with mortality to that of lactate and renin in the VICTAS cohort of sepsis patients at baseline (day 0) by receiver operating characteristic (ROC) and Kaplan–Meier curve analyses. Serum concentration of Angiotensinogen was more strongly associated with 30-day mortality than either the serum concentrations of renin or lactate in sepsis patients. Moreover, the clinical assessment of Angiotensinogen may have distinct advantages over the typical measures of renin. The assessment of intact Angiotensinogen may potentially facilitate more precise therapeutic approaches (including exogenous angiotensin II) to restore a dysfunctional RAS and improve patient outcomes. Additional prospective validation studies are clearly required for this biomarker in the future.
{"title":"Stronger association of intact angiotensinogen with mortality than lactate or renin in critical illness: post-hoc analysis from the VICTAS trial","authors":"Mark C. Chappell, Christopher L. Schaich, Laurence W. Busse, Greg S. Martin, Jonathan E. Sevransky, Jeremiah K. Hinson, Ashish K. Khanna","doi":"10.1186/s13054-024-05120-w","DOIUrl":"https://doi.org/10.1186/s13054-024-05120-w","url":null,"abstract":"Sepsis and septic shock remain global healthcare problems associated with high mortality rates despite best therapy efforts. Circulating biomarkers may identify those patients at risk for poor outcomes, however, current biomarkers, most prominently lactate, are non-specific and have an inconsistent impact on prognosis and/or disease management. Activation of the renin-angiotensin- system (RAS) is an early event in sepsis patients and elevated levels of circulating renin are more predictive of worse outcomes than lactate. The precursor protein Angiotensinogen is another key component of the circulating RAS; it is the only known substrate for renin and the ultimate source of the vasopressor Angiotensin II (Ang II). We postulate that lower Angiotensinogen concentrations may reflect a dysfunctional RAS characterized by high renin concentrations but attenuated Ang II generation, which is disproportionate to the high renin response and may compromise adequate support of blood pressure and tissue perfusion in septic patients. The current study compared the association between serum Angiotensinogen with mortality to that of lactate and renin in the VICTAS cohort of sepsis patients at baseline (day 0) by receiver operating characteristic (ROC) and Kaplan–Meier curve analyses. Serum concentration of Angiotensinogen was more strongly associated with 30-day mortality than either the serum concentrations of renin or lactate in sepsis patients. Moreover, the clinical assessment of Angiotensinogen may have distinct advantages over the typical measures of renin. The assessment of intact Angiotensinogen may potentially facilitate more precise therapeutic approaches (including exogenous angiotensin II) to restore a dysfunctional RAS and improve patient outcomes. Additional prospective validation studies are clearly required for this biomarker in the future.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"17 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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