Pub Date : 2025-04-23DOI: 10.1186/s13054-025-05399-3
Elena Ribet Buse, Julius J. Grunow, Claudia D. Spies, Björn Weiss, Nicolas Paul
Expanding follow-up services for survivors of critical illness requires short and reliable instrument sets. The WHO Disability Assessment Schedule (WHODAS) 2.0 and the EuroQol 5-Dimensions 5-Level (EQ-5D-5L) are recommended to assess disability and health-related quality of life (HrQoL), respectively. As they may measure partially overlapping constructs, we assessed their relationship. We conducted a secondary analysis of the multicenter cluster-randomized controlled Enhanced Recovery after Intensive Care (ERIC) trial (ClinicalTrials.gov: NCT03671447). At follow-ups scheduled 6 months after ICU discharge, critical illness survivors and caregivers completed the EQ-5D-5L, the patient-reported and the proxy-reported 12-item WHODAS 2.0. We employed local polynomial regressions, correlation coefficients, and linear regressions to analyze the global and domain-specific relationships between the EQ-5D-5L and the WHODAS 2.0. We analyzed 700 patients with a median EQ-5D-5L index value of 0.81 [IQR 0.52 to 0.94], a median patient-reported WHODAS 2.0 sum score of 11 [IQR 3 to 23], and a median proxy-reported WHODAS 2.0 sum score of 16 [IQR 6 to 28]. The EQ-5D-5L index value highly correlated with patient-reported (Spearman: − 0.84 [95% CI − 0.86 to − 0.82]) and proxy-reported (Spearman: − 0.70 [− 0.76 to − 0.64]) WHODAS 2.0 sum scores. Corresponding domains were also highly correlated, with the patient-reported WHODAS 2.0 aligning more closely with the EQ-5D-5L than the proxy-reported WHODAS 2.0. We found ceiling and floor effects for both instruments, indicating limitations for detecting mild disabilities and high HrQoL. In multivariable linear regressions, the patient-reported and proxy-reported WHODAS 2.0 sum scores (both − 0.02 [95% CI − 0.02 to − 0.02], p < 0.01) and WHODAS 2.0 domain scores for mobility, self-care, and life activities were predictors of the EQ-5D-5L index value and respective EQ-5D-5L domain scores. Our results suggest a high correlation between the patient-reported and proxy-reported WHODAS 2.0 and the EQ-5D-5L, particularly in their corresponding domains. To economize post-ICU assessments, there may be no need to use both instruments simultaneously.
{"title":"Health-related quality of life correlates with patient-reported and proxy-reported disability in critical illness survivors: a secondary analysis of the ERIC trial","authors":"Elena Ribet Buse, Julius J. Grunow, Claudia D. Spies, Björn Weiss, Nicolas Paul","doi":"10.1186/s13054-025-05399-3","DOIUrl":"https://doi.org/10.1186/s13054-025-05399-3","url":null,"abstract":"Expanding follow-up services for survivors of critical illness requires short and reliable instrument sets. The WHO Disability Assessment Schedule (WHODAS) 2.0 and the EuroQol 5-Dimensions 5-Level (EQ-5D-5L) are recommended to assess disability and health-related quality of life (HrQoL), respectively. As they may measure partially overlapping constructs, we assessed their relationship. We conducted a secondary analysis of the multicenter cluster-randomized controlled Enhanced Recovery after Intensive Care (ERIC) trial (ClinicalTrials.gov: NCT03671447). At follow-ups scheduled 6 months after ICU discharge, critical illness survivors and caregivers completed the EQ-5D-5L, the patient-reported and the proxy-reported 12-item WHODAS 2.0. We employed local polynomial regressions, correlation coefficients, and linear regressions to analyze the global and domain-specific relationships between the EQ-5D-5L and the WHODAS 2.0. We analyzed 700 patients with a median EQ-5D-5L index value of 0.81 [IQR 0.52 to 0.94], a median patient-reported WHODAS 2.0 sum score of 11 [IQR 3 to 23], and a median proxy-reported WHODAS 2.0 sum score of 16 [IQR 6 to 28]. The EQ-5D-5L index value highly correlated with patient-reported (Spearman: − 0.84 [95% CI − 0.86 to − 0.82]) and proxy-reported (Spearman: − 0.70 [− 0.76 to − 0.64]) WHODAS 2.0 sum scores. Corresponding domains were also highly correlated, with the patient-reported WHODAS 2.0 aligning more closely with the EQ-5D-5L than the proxy-reported WHODAS 2.0. We found ceiling and floor effects for both instruments, indicating limitations for detecting mild disabilities and high HrQoL. In multivariable linear regressions, the patient-reported and proxy-reported WHODAS 2.0 sum scores (both − 0.02 [95% CI − 0.02 to − 0.02], p < 0.01) and WHODAS 2.0 domain scores for mobility, self-care, and life activities were predictors of the EQ-5D-5L index value and respective EQ-5D-5L domain scores. Our results suggest a high correlation between the patient-reported and proxy-reported WHODAS 2.0 and the EQ-5D-5L, particularly in their corresponding domains. To economize post-ICU assessments, there may be no need to use both instruments simultaneously.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"108 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862763","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 : 2025-04-23DOI: 10.1186/s13054-025-05418-3
Wenxiao Zhang
<p>Dear Editor,</p><p>I read with great interest the study by Xie et al. published in Critical Care and carefully reviewed their clinical trial registration details (NCT06524765) [1]. Although this study holds significant clinical value, there are still certain issues that need to be addressed.</p><p>First, it appears that there may be some deviations from the clinical trial protocol provided (NCT06524765). According to the study protocol, the primary outcome was defined as the difference in ARGs abundance; however, this outcome does not seem to have been fully addressed in the study. Additionally, several secondary outcomes were not presented. Specifically, important metrics related to quality-of-life assessments, including the Patient Health Questionnaire (PHQ-9) score, Symptom Checklist 90 (SCL-90) score, Perceived Stress Scale (PSS) score, International Physical Activity Questionnaire (IPAQ) score, and Pittsburgh Sleep Quality Index (PSQI) score, appear to be missing. These omissions raise some questions regarding the completeness of the study’s findings.</p><p>Second, the authors claim that gender is the factor influencing microbiome differences among healthcare workers. Given that the majority of nurses in China are female, the observed differences could potentially be attributed to occupational characteristics rather than solely to gender. It would be helpful if the authors could provide additional details on the occupational categories of male and female healthcare workers to further clarify this issue.</p><p>Finally, the authors did not make any multiple corrections to the <i>P</i>-value in this study. In microbiome research, multiple testing corrections for p-values should be applied to decrease the probability of false positives, making the final conclusions more reliable. Besides, it seems that a sample size calculation based on the primary outcome was not conducted. Considering that a sample size of 40 is relatively small for a microbiome study, this may have an impact on the statistical robustness of the results. For instance, while the authors suggest that there is no statistically significant difference in ARGs between healthcare workers and healthy individuals, this result could potentially be influenced by the sample size, which may not be sufficient to detect such differences.</p><p>I hope the authors can take these issues into careful consideration.</p><p>None</p><ol data-track-component="outbound reference" data-track-context="references section"><li data-counter="1."><p>Xie B, Dong C, Zhao X, et al. Structural and functional alteration of the gut microbiomes in ICU staff: a cross-sectional analysis. Crit Care. 2025;29:141.</p><p>Article PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden="true" focusable="false" height="16" role="img" width="16"><use xlink:href="#icon-eds-i-download-medium" xmlns:xlink="http://www.w3.org/1999/xlink"></use></svg></p><p>None.</p><h3>Authors and Affiliation
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{"title":"Letter to the editor regarding “Structural and functional alteration of the gut microbiomes in ICU staff: a cross-sectional analysis”","authors":"Wenxiao Zhang","doi":"10.1186/s13054-025-05418-3","DOIUrl":"https://doi.org/10.1186/s13054-025-05418-3","url":null,"abstract":"<p>Dear Editor,</p><p>I read with great interest the study by Xie et al. published in Critical Care and carefully reviewed their clinical trial registration details (NCT06524765) [1]. Although this study holds significant clinical value, there are still certain issues that need to be addressed.</p><p>First, it appears that there may be some deviations from the clinical trial protocol provided (NCT06524765). According to the study protocol, the primary outcome was defined as the difference in ARGs abundance; however, this outcome does not seem to have been fully addressed in the study. Additionally, several secondary outcomes were not presented. Specifically, important metrics related to quality-of-life assessments, including the Patient Health Questionnaire (PHQ-9) score, Symptom Checklist 90 (SCL-90) score, Perceived Stress Scale (PSS) score, International Physical Activity Questionnaire (IPAQ) score, and Pittsburgh Sleep Quality Index (PSQI) score, appear to be missing. These omissions raise some questions regarding the completeness of the study’s findings.</p><p>Second, the authors claim that gender is the factor influencing microbiome differences among healthcare workers. Given that the majority of nurses in China are female, the observed differences could potentially be attributed to occupational characteristics rather than solely to gender. It would be helpful if the authors could provide additional details on the occupational categories of male and female healthcare workers to further clarify this issue.</p><p>Finally, the authors did not make any multiple corrections to the <i>P</i>-value in this study. In microbiome research, multiple testing corrections for p-values should be applied to decrease the probability of false positives, making the final conclusions more reliable. Besides, it seems that a sample size calculation based on the primary outcome was not conducted. Considering that a sample size of 40 is relatively small for a microbiome study, this may have an impact on the statistical robustness of the results. For instance, while the authors suggest that there is no statistically significant difference in ARGs between healthcare workers and healthy individuals, this result could potentially be influenced by the sample size, which may not be sufficient to detect such differences.</p><p>I hope the authors can take these issues into careful consideration.</p><p>None</p><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Xie B, Dong C, Zhao X, et al. Structural and functional alteration of the gut microbiomes in ICU staff: a cross-sectional analysis. Crit Care. 2025;29:141.</p><p>Article PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><p>None.</p><h3>Authors and Affiliation","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"32 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862749","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}
Acute hypernatremia is a prevalent electrolyte imbalance in the intensive care unit (ICU), closely associated with the severity of patients’ conditions. This study employs animal experimentation to investigate the effects of varying sodium reduction rates on the central nervous system in acute hypernatremia, aiming to identify the optimal rate of sodium reduction. A stepwise sodium titration approach was used to establish an acute hypernatremia model, targeting a sodium increase of 0.5 mEq/L per hour (target serum sodium: a rise of 15 mEq/L within 48 h from baseline). Subsequently, a stepwise sodium decrement method was applied to reduce sodium levels to baseline. The study included four groups with different target sodium reduction rates: 1 mEq/L/h (Slow group), 2 mEq/L/h (Middle group), 3 mEq/L/h (Fast group), and Sham surgery group. Blood sodium and potassium levels, as well as urine sodium and potassium, were measured at various time points; central venous pressure (CVP) and intracranial pressure (ICP) were monitored; fluid intake and output were recorded to calculate fluid balance. After sodium reduction, brain tissue was extracted for pathological examination. Twenty adult, healthy male rabbits were randomly assigned to four groups (five rabbits per group). Before and after sodium reduction, the ICP significantly increased in the Fast group from 7.00 ± 0.71 to 13.20 ± 2.95 and in the Middle group from 6.80 ± 0.45 to 11.40 ± 0.89 (p = 0.015 and p = 0.000, respectively); the Slow group showed no significant change in ICP. Pathological findings revealed edema and disorganized brain tissue in the cerebral cortex and brainstem in the Fast and Middle groups, with statistically significant differences compared to the sham-operated group in semi-quantitative analysis. For acute hypernatremia that develops within 48 h, sodium reduction rates exceeding 1 mEq/L/h are associated with greater increases in ICP and more severe brain edema. Therefore, for managing acute hypernatremia,our result prompted that sodium reduction rates might not exceed 1 mEq/L/h.
{"title":"The impact of different rates of sodium reduction on the central nervous system in acute hypernatremia in rabbits","authors":"Geng Xue, Hongyu Wu, Ruidong Feng, Ling Ma, Rui Cao, Rongli Yang, Shuo Wu","doi":"10.1186/s13054-025-05377-9","DOIUrl":"https://doi.org/10.1186/s13054-025-05377-9","url":null,"abstract":"Acute hypernatremia is a prevalent electrolyte imbalance in the intensive care unit (ICU), closely associated with the severity of patients’ conditions. This study employs animal experimentation to investigate the effects of varying sodium reduction rates on the central nervous system in acute hypernatremia, aiming to identify the optimal rate of sodium reduction. A stepwise sodium titration approach was used to establish an acute hypernatremia model, targeting a sodium increase of 0.5 mEq/L per hour (target serum sodium: a rise of 15 mEq/L within 48 h from baseline). Subsequently, a stepwise sodium decrement method was applied to reduce sodium levels to baseline. The study included four groups with different target sodium reduction rates: 1 mEq/L/h (Slow group), 2 mEq/L/h (Middle group), 3 mEq/L/h (Fast group), and Sham surgery group. Blood sodium and potassium levels, as well as urine sodium and potassium, were measured at various time points; central venous pressure (CVP) and intracranial pressure (ICP) were monitored; fluid intake and output were recorded to calculate fluid balance. After sodium reduction, brain tissue was extracted for pathological examination. Twenty adult, healthy male rabbits were randomly assigned to four groups (five rabbits per group). Before and after sodium reduction, the ICP significantly increased in the Fast group from 7.00 ± 0.71 to 13.20 ± 2.95 and in the Middle group from 6.80 ± 0.45 to 11.40 ± 0.89 (p = 0.015 and p = 0.000, respectively); the Slow group showed no significant change in ICP. Pathological findings revealed edema and disorganized brain tissue in the cerebral cortex and brainstem in the Fast and Middle groups, with statistically significant differences compared to the sham-operated group in semi-quantitative analysis. For acute hypernatremia that develops within 48 h, sodium reduction rates exceeding 1 mEq/L/h are associated with greater increases in ICP and more severe brain edema. Therefore, for managing acute hypernatremia,our result prompted that sodium reduction rates might not exceed 1 mEq/L/h.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"6 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862745","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 : 2025-04-23DOI: 10.1186/s13054-025-05329-3
Wenyu Wu, Wanning Lan, Xin Jiao, Kai Wang, Yawen Deng, Rui Chen, Ruifeng Zeng, Jun Li
Sepsis-associated acute kidney injury (S-AKI) is a severe complication characterized by high morbidity and mortality, driven by multi-organ dysfunction. Recent evidence suggests that pyroptosis, a form of programmed cell death distinct from apoptosis and necrosis, plays a critical role in the pathophysiology of S-AKI. This review examines the mechanisms of pyroptosis, focusing on inflammasome activation (e.g., NLRP3), caspase-mediated processes, and the role of Gasdermin D in renal tubular damage. We also discuss the contributions of inflammatory mediators, oxidative stress, and potential therapeutic strategies targeting pyroptosis, including inflammasome inhibitors, caspase inhibitors, and anti-inflammatory therapies. Lastly, we highlight the clinical implications and challenges in translating these findings into effective treatments, underscoring the need for personalized medicine approaches in managing S-AKI.
{"title":"Pyroptosis in sepsis-associated acute kidney injury: mechanisms and therapeutic perspectives","authors":"Wenyu Wu, Wanning Lan, Xin Jiao, Kai Wang, Yawen Deng, Rui Chen, Ruifeng Zeng, Jun Li","doi":"10.1186/s13054-025-05329-3","DOIUrl":"https://doi.org/10.1186/s13054-025-05329-3","url":null,"abstract":"Sepsis-associated acute kidney injury (S-AKI) is a severe complication characterized by high morbidity and mortality, driven by multi-organ dysfunction. Recent evidence suggests that pyroptosis, a form of programmed cell death distinct from apoptosis and necrosis, plays a critical role in the pathophysiology of S-AKI. This review examines the mechanisms of pyroptosis, focusing on inflammasome activation (e.g., NLRP3), caspase-mediated processes, and the role of Gasdermin D in renal tubular damage. We also discuss the contributions of inflammatory mediators, oxidative stress, and potential therapeutic strategies targeting pyroptosis, including inflammasome inhibitors, caspase inhibitors, and anti-inflammatory therapies. Lastly, we highlight the clinical implications and challenges in translating these findings into effective treatments, underscoring the need for personalized medicine approaches in managing S-AKI. ","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"7 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866755","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}
<p>To the Editor,</p><p>We thank Drs. Stevic, Argaud, and Cour for their interest in our recent article entitled <i>Cardiovascular Effects of Lactate in Healthy Adults</i> [1]. Indeed, utilizing a racemic hypertonic sodium lactate (HSL) solution, the composition of the enantiomers <span>l</span>- and <span>d</span>-lactate is balanced, and we agree that recognition of chirality is essential to further comprehend our results. However, additional important aspects must be considered to fully explain the potential hemodynamic benefits of HSL treatment.</p><p>The commentary by Stevic et al. [2] raises concerns regarding potential toxicity from <span>d</span>-lactate accumulation, particularly in critically ill patients. While it is true that <span>d</span>-lactate is metabolized less efficiently than <span>l</span>-lactate [3], the clinical relevance of this remains unclear. In healthy individuals, <span>d</span>-lactate is present at negligible concentrations and is readily excreted in the urine [4]. In our study, we only measured circulating <span>l</span>-lactate, and thus, we can only speculate on the levels of <span>d</span>-lactate [1]. Interestingly, a prior study of healthy participants utilizing a similar infusion regimen to ours demonstrated comparable circulating levels of <span>l</span>-lactate (2.8–4.0 mmol/L), with slightly lower levels of <span>d</span>-lactate (1.7–3.0 mmol/L) [4]. This difference was attributed to lower endogenous <span>d</span>-lactate production. Importantly, metabolic clearance of <span>d</span>-lactate appeared to be efficient, despite preferential utilization of <span>l</span>-lactate. While <span>l</span>-lactate is typically converted to pyruvate via <span>l</span>-lactate dehydrogenase (L-LDH), <span>d</span>-lactate may also be converted to pyruvate through D-LDH, an enzyme enriched in the liver and kidneys [5]. These findings suggest that <span>d</span>-lactate, although less abundant in the bloodstream, may still undergo metabolic processes.</p><p>Despite concerns regarding potential <span>d</span>-lactate toxicity, no studies to date have demonstrated clinically relevant adverse effects following exogenous administration in humans at doses comparable to those used in our study. Notably, endogenous accumulation of both <span>l</span>- and <span>d</span>-lactate can contribute to lactic acidosis [6]. While <span>l</span>-lactic acidosis is commonly observed in clinical settings, <span>d</span>-lactic acidosis is rare and often associated with short-bowel syndrome, where excessive <span>d</span>-lactate is produced and absorbed from the gastrointestinal tract [7]. Furthermore, although <span>d</span>-lactate accumulation has been linked to neurological symptoms in patients with mutations affecting D-LDH function, these conditions are often accompanied by the accumulation of multiple organic acids, complicating the interpretation of <span>d</span>-lactate toxicity [8]. Importantly, no side effects resembling
Stevic 等人的评论还提出了一个重要问题,即 HSL 诱导的左心室功能改善是源于对心肌细胞的直接作用还是间接的全身机制。虽然我们的研究不是为了分离这些效应,但最近的动物研究提供了有价值的见解。大剂量外消旋 HSL 给药已被证明可增加健康猪的心输出量并降低全身血管阻力 [9]。然而,左心室收缩力并未受到明显影响。在心源性休克模型中,低剂量输注相同的 HSL 溶液同样能降低全身血管阻力,同时还能改善心脏收缩力,这表明 HSL 有直接的肌力作用 [10]。事实上,随着心肌线粒体功能的改善,直接的新陈代谢效应也被注意到。因此,乳酸盐治疗对心血管的影响可能与剂量和病理生理学有关。虽然之前的一项研究没有观察到乳酸盐对离体心脏的直接影响,但这可能是受到此类实验装置固有的突然缓冲转移的影响[13]。值得注意的是,最近的研究结果表明,乳酸盐处理可提高离体心脏的左心室显像压,并以剂量依赖的方式诱导离体动脉的血管舒张[15],这证实了大型动物研究和我们人类队列的观察结果。总之,虽然目前的证据并不支持外消旋 HSL 对人体造成危害,但我们同意 Stevic 等人的观点,即在考虑使用外消旋 HSL 之前,有必要进行进一步的研究。Berg-Hansen K、Gopalasingam N、Pedersen MGB、Nyvad JT、Rittig N、Søndergaard E、Wiggers H、Møller N、Nielsen R. 健康成人乳酸对心血管的影响。Crit Care.2025; 29:30.Article PubMed PubMed Central Google Scholar Stevic N, Argaud L, Cour M. 健康成人乳酸对心血管的影响:d-乳酸,被遗忘的对映体。Crit Care.2025; 29:122.Article PubMed PubMed Central Google Scholar Connor H, Woods HF, Ledingham JG.正常人体内 d(-)- 和 l(+)- 乳酸钠的动力学和利用率比较。Ann Nutr Metab.1983;27:481-7.Article CAS PubMed Google Scholar Oh MS, Uribarri J, Alveranga D, Lazar I, Bazilinski N, Carroll HJ.男性对 d-乳酸的代谢利用和肾脏处理。代谢。1985; 34:621-5.Article CAS PubMed Google Scholar Jin S, Chen X, Yang J, Ding J. Lactate dehydrogenase d is a general dehydrogenase for d-2-hydroxyacids and is associated with d-lactic acidosis.Nat Commun.2023;14:1-13.Article PubMed PubMed Central Google Scholar Kraut JA, Madias NE.乳酸酸中毒。N Engl J Med.2014;371:2309-19.Article PubMed Google Scholar Uribarri J, Oh MS, Carroll HJ. 乳酸酸中毒:临床表现、生化特征和病理生理机制综述。医学(巴尔的摩)。1998;77:73-82.Article CAS PubMed Google Scholar Monroe GR, van Eerde AM, Tessadori F, Duran KJ, Savelberg SMC, van Alfen JC, Terhal PA, van der Crabben SN, Lichtenbelt KD, Fuchs SA, et al. Identification of human d lactate dehydrogenase deficiency.Nat Commun.https://doi.org/10.1038/s41467-019-09458-6.Article CAS PubMed PubMed Central Google Scholar Hørsdal OK, Moeslund N, Berg-Hansen K, Nielsen R, Møller N, Eiskjær H, Wiggers H, Gopalasingam N. Lactate infusion elevates cardiac output through increased heart rate and decreased vascular resistance: a randomised, blinded, crosssover trial in a healthy porcine model.J Transl Med.2024; 22:1-14.Article Google Scholar Hørsdal OK, Ellegaard MS, Larsen AM, Guldbrandsen H, Moeslund N, Møller JE, Kristian O, Helgestad L, Ravn HB, Wiggers H, et al. Lactate infusion improves cardiac function in a porcine model of ischemic cardiogenic shock.Crit Care.2025. https://doi.org/10.1186/s13054-025-05346-2.Article PubMed PubMed Central Google Scholar Annoni F、Su F、Peluso L、Lisi I、Caruso E、Pischiutta F、Gouvea Bogossian E、Garcia B、Njimi H、Vincent JL 等:输注 DL-3-ß-hydroxybutyrate 钠可减少实验性心脏骤停患者复苏后的脑损伤生物标志物。Crit Care.https://doi.org/10.1186/s13054-024-05106-8.Article PubMed PubMed Central Google Scholar Nalos M, Leverve XM, Huang SJ, Weisbrodt L, Parkin R, Seppelt IM, Ting I, Mclean AS.输注半摩尔乳酸钠可改善急性心衰患者的心脏功能:随机对照临床试验。Crit Care.2014;18:1-9.
{"title":"Cardiovascular effects of lactate in healthy adults: d-lactate, the forgotten enantiomer—authors' reply","authors":"Kristoffer Berg-Hansen, Mette Glavind Bülow Pedersen, Nigopan Gopalasingam, Nikolaj Rittig, Esben Søndergaard, Niels Møller, Roni Nielsen","doi":"10.1186/s13054-025-05407-6","DOIUrl":"https://doi.org/10.1186/s13054-025-05407-6","url":null,"abstract":"<p>To the Editor,</p><p>We thank Drs. Stevic, Argaud, and Cour for their interest in our recent article entitled <i>Cardiovascular Effects of Lactate in Healthy Adults</i> [1]. Indeed, utilizing a racemic hypertonic sodium lactate (HSL) solution, the composition of the enantiomers <span>l</span>- and <span>d</span>-lactate is balanced, and we agree that recognition of chirality is essential to further comprehend our results. However, additional important aspects must be considered to fully explain the potential hemodynamic benefits of HSL treatment.</p><p>The commentary by Stevic et al. [2] raises concerns regarding potential toxicity from <span>d</span>-lactate accumulation, particularly in critically ill patients. While it is true that <span>d</span>-lactate is metabolized less efficiently than <span>l</span>-lactate [3], the clinical relevance of this remains unclear. In healthy individuals, <span>d</span>-lactate is present at negligible concentrations and is readily excreted in the urine [4]. In our study, we only measured circulating <span>l</span>-lactate, and thus, we can only speculate on the levels of <span>d</span>-lactate [1]. Interestingly, a prior study of healthy participants utilizing a similar infusion regimen to ours demonstrated comparable circulating levels of <span>l</span>-lactate (2.8–4.0 mmol/L), with slightly lower levels of <span>d</span>-lactate (1.7–3.0 mmol/L) [4]. This difference was attributed to lower endogenous <span>d</span>-lactate production. Importantly, metabolic clearance of <span>d</span>-lactate appeared to be efficient, despite preferential utilization of <span>l</span>-lactate. While <span>l</span>-lactate is typically converted to pyruvate via <span>l</span>-lactate dehydrogenase (L-LDH), <span>d</span>-lactate may also be converted to pyruvate through D-LDH, an enzyme enriched in the liver and kidneys [5]. These findings suggest that <span>d</span>-lactate, although less abundant in the bloodstream, may still undergo metabolic processes.</p><p>Despite concerns regarding potential <span>d</span>-lactate toxicity, no studies to date have demonstrated clinically relevant adverse effects following exogenous administration in humans at doses comparable to those used in our study. Notably, endogenous accumulation of both <span>l</span>- and <span>d</span>-lactate can contribute to lactic acidosis [6]. While <span>l</span>-lactic acidosis is commonly observed in clinical settings, <span>d</span>-lactic acidosis is rare and often associated with short-bowel syndrome, where excessive <span>d</span>-lactate is produced and absorbed from the gastrointestinal tract [7]. Furthermore, although <span>d</span>-lactate accumulation has been linked to neurological symptoms in patients with mutations affecting D-LDH function, these conditions are often accompanied by the accumulation of multiple organic acids, complicating the interpretation of <span>d</span>-lactate toxicity [8]. Importantly, no side effects resembling ","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"1 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862744","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 : 2025-04-23DOI: 10.1186/s13054-025-05405-8
Ricardo Miguel Rodrigues-Gomes, Ángela Prieto Campo, Rosa Martinez Rolán, Miguel Gelabert-González
Some studies refer to the increase in intracranial pressure (ICP) with chest physiotherapy techniques but without any randomized controlled trials that evaluate the safety of the manual rapid chest compression technique in patients with severe acute brain injuries on invasive mechanical ventilation. Our research question examines whether intracranial and cerebral perfusion pressures significantly change during rapid chest compression technique. A prospective, randomized, single-blinded controlled trial of acute neurocritical patients under mechanical ventilation was performed. The intervention group was subjected to rapid chest compression, and the control group received mechanical passive inferior limbs mobilization. The outcomes were intracranial pressure, cerebral perfusion pressure, blood partial pressure of oxygen and carbon dioxide, and inspiratory and expiratory peak flows. Between May 2021 and December 2023, 50 patients (aged 56.3 years), 66% females, were randomized into two groups (25 controls and 25 interventions). The ICP and cerebral perfusion pressure (CPP) did not significantly differ between the groups at any of the studied times. Intragroup analysis revealed significant decreases in the ICP and CPP in the intervention group, with posterior recovery in both groups. The CPP significantly decreased in the control group but did not reach the preintervention values at the last measurement time. PaCO2 was significantly lower in the intervention group than in the control group at the end of the study. The rapid chest compression technique did not increase the ICP during its application or even 30 min after it. The ICP showed a slight significant decrease during the application of the rapid chest compression technique but reached the previous values in the posterior 30 min. CPP had a similar behavior but did not completely recover in both groups. Trial registration: NCT03609866. Registered on 08/01/2018.
{"title":"Effects of rapid chest compression technique on intracranial and cerebral perfusion pressures in acute neurocritical patients: a randomized controlled trial","authors":"Ricardo Miguel Rodrigues-Gomes, Ángela Prieto Campo, Rosa Martinez Rolán, Miguel Gelabert-González","doi":"10.1186/s13054-025-05405-8","DOIUrl":"https://doi.org/10.1186/s13054-025-05405-8","url":null,"abstract":"Some studies refer to the increase in intracranial pressure (ICP) with chest physiotherapy techniques but without any randomized controlled trials that evaluate the safety of the manual rapid chest compression technique in patients with severe acute brain injuries on invasive mechanical ventilation. Our research question examines whether intracranial and cerebral perfusion pressures significantly change during rapid chest compression technique. A prospective, randomized, single-blinded controlled trial of acute neurocritical patients under mechanical ventilation was performed. The intervention group was subjected to rapid chest compression, and the control group received mechanical passive inferior limbs mobilization. The outcomes were intracranial pressure, cerebral perfusion pressure, blood partial pressure of oxygen and carbon dioxide, and inspiratory and expiratory peak flows. Between May 2021 and December 2023, 50 patients (aged 56.3 years), 66% females, were randomized into two groups (25 controls and 25 interventions). The ICP and cerebral perfusion pressure (CPP) did not significantly differ between the groups at any of the studied times. Intragroup analysis revealed significant decreases in the ICP and CPP in the intervention group, with posterior recovery in both groups. The CPP significantly decreased in the control group but did not reach the preintervention values at the last measurement time. PaCO2 was significantly lower in the intervention group than in the control group at the end of the study. The rapid chest compression technique did not increase the ICP during its application or even 30 min after it. The ICP showed a slight significant decrease during the application of the rapid chest compression technique but reached the previous values in the posterior 30 min. CPP had a similar behavior but did not completely recover in both groups. Trial registration: NCT03609866. Registered on 08/01/2018.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"1 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862762","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 : 2025-04-23DOI: 10.1186/s13054-025-05413-8
Johannes Ehler, Axel Petzold
<p>Dear Editor,</p><p>We read with great interest the recent publication by Cheng et al., investigating the role of haloperidol in delirium [1]. We acknowledge the authors’ diligent selection of studies for comparison, but wonder that landmark studies came to a diametrically opposed conclusion [2, 3]. There is need for a balanced interpretation of the presumed meta-analytical benefits of haloperidol regarding survival and delirium duration, with the interpretation of presumably fewer serious adverse events (SAEs) [1,2,3]. There are three key questions on which we would like to learn the authors’ opinion.</p><p>Firstly, the consistent comparison of haloperidol against placebo, while providing a baseline, overlooks the significant evolution towards a multimodal approach in delirium therapy. Current best practices emphasize a holistic strategy integrating non-pharmacological interventions for both prevention and treatment, with pharmacological agents reserved for specific indications [4]. The study does not address the contemporary core delirium care, particularly the extent to which non-pharmacological strategies were implemented. This omission is critical, given the increasing emphasis on non-pharmacological recommendations by leading societies such as the European Society of Anaesthesiology and Intensive Care (ESAIC) [4]. Does focusing solely on pharmacological intervention risks not present an incomplete and potentially biased perspective on delirium management?</p><p>Secondly, the observation of a reduced number of rescue benzodiazepine treatments through application of haloperidol warrants further scrutiny. Do benzodiazepines itself not have a pro-delirogenic potential and are therefore discouraged for treatment of delirium [4]?</p><p>Thirdly, the lack of a significant effect on duration of ventilation raises important questions, particularly concerning the broader context of ICU management. Prolonged ventilation is a multifactorial issue. Does attributing it solely to delirium not overlook the potential influence of sedative medication dosages, paradoxically including haloperidol itself?</p><p>Furthermore, we have concerns regarding the presentation of data in Table 2 on prevention of delirium [1]. The presentation of "benefits (%)" might be misleading when the Risk Ratio lacks significance. Similarly, the "any benefit" descriptor in Table 1 [1], while highlighting potential advantages, could be misinterpreted as a definitive recommendation for universal haloperidol use. In clinical practice there will be no “one drug fits all solution”.</p><p>In conclusion, we believe that while the study provides valuable data on the efficacy of haloperidol compared to placebo [1], a balanced interpretation should also include:</p><ul><li><p>Current guidelines increasingly support non-pharmacological strategies as the cornerstone of delirium management [4], moving away from a "one drug fits all" approach.</p></li><li><p>Haloperidol carries a risk of QT
亲爱的编辑,我们怀着极大的兴趣阅读了 Cheng 等人最近发表的关于氟哌啶醇在谵妄中作用的研究[1]。我们对作者精心挑选的对比研究表示认可,但对具有里程碑意义的研究得出截然相反的结论感到惊奇[2, 3]。对于氟哌啶醇在存活率和谵妄持续时间方面的荟萃分析假定益处,以及严重不良事件(SAEs)的假定较少,需要有一个平衡的解释[1,2,3]。首先,氟哌啶醇与安慰剂的一致性比较虽然提供了一个基线,但忽略了谵妄治疗向多模式方法的重大演变。目前的最佳实践强调综合策略,将非药物干预措施用于预防和治疗,而药物则用于特定的适应症[4]。该研究并未涉及当代核心谵妄护理,尤其是非药物治疗策略的实施程度。鉴于欧洲麻醉学和重症监护学会(ESAIC)等主要学会越来越重视非药物治疗建议,这一疏忽至关重要[4]。仅关注药物干预的风险是否会对谵妄管理提出不全面且可能存在偏见的观点?其次,通过应用氟哌啶醇而减少苯二氮卓类药物抢救治疗次数的观察结果值得进一步研究。苯二氮卓类药物本身是否具有促脱氢潜力,因此不鼓励用于治疗谵妄[4]?延长通气时间是一个多因素问题。将其完全归咎于谵妄是否忽视了镇静药物剂量的潜在影响,包括氟哌啶醇本身?当风险比不显著时,"获益(%)"的表述可能会产生误导。同样,表 1 [1]中的 "任何获益 "描述在强调潜在优势的同时,也可能被误解为普遍使用氟哌啶醇的明确建议。总之,我们认为虽然该研究提供了氟哌啶醇与安慰剂相比疗效的宝贵数据[1],但平衡的解释还应包括:当前的指南越来越支持将非药物策略作为谵妄治疗的基石[4],摒弃了 "一药灵 "的方法。氟哌啶醇有导致 QTc 延长的风险,因此在高危人群(如谵妄发生率较高的心脏手术患者)中必须慎重考虑。氟哌啶醇应被视为多模式谵妄管理策略的一个潜在组成部分,而不应被视为一种单一的治疗方案。未来的研究应优先比较有无添加氟哌啶醇等特定药物的多模式谵妄护理,以更好地确定其在综合治疗框架中的作用。我们期待阅读作者对这些观点的看法,以便更平衡地理解氟哌啶醇在当代谵妄治疗中的作用,并指导这一关键领域未来的研究工作。ESAIC:欧洲麻醉学和重症监护学会NMS:神经性恶性综合征SAE:严重不良事件Cheng SL, Hsu TW, Kao YC, Yu CL, Thompson T, Carvalho AF, et al:贝叶斯和频数荟萃分析。Crit Care.2025; 29:126.Article PubMed PubMed Central Google Scholar Andersen-Ranberg NC, Poulsen LM, Perner A, Wetterslev J, Estrup S, Hästbacka J, et al. Haloperidol for the treatment of delirium in ICU patients.N Engl J Med.2022;387:2425-35.Article CAS PubMed Google Scholar Girard TD, Ely EW, Investigators MIND-USA.氟哌啶醇和齐拉西酮治疗重症谵妄。N Engl J Med.2018;379:2506-16.Article CAS PubMed PubMed Central Google Scholar Aldecoa C, Bettelli G, Bilotta F, Sanders RD, Aceto P, Audisio R, et al. Update of the European Society of Anaesthesiology and intensive care medicine evidence-based and consensus-based guideline on postoperative delirium in adult patients.Eur J Anaesthesiol. 作者和工作单位德国耶拿,耶拿大学医院麻醉学和重症监护医学系Johannes Ehler英国国立神经学和神经外科医院分子神经科学系,皇后广场神经学研究所、Moorfields Eye Hospital, UCL, London, UKAxel Petzold作者Johannes Ehler查看作者发表的论文您也可以在PubMed Google ScholarAxel Petzold查看作者发表的论文您也可以在PubMed Google ScholarContributionsA.作者信息JE作为德国麻醉学和重症监护医学学会神经麻醉科学工作组的第二发言人担任领导职务。通讯作者Johannes Ehler。伦理批准和参与同意不适用。同意发表不适用。利益冲突JE & AP声明有利益冲突。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,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,并说明是否进行了更改。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,则您需要直接从版权所有者处获得许可。如需查看该许可的副本,请访问 http://creativecommons.org/licenses/by/4.0/.Reprints and permissionsCite this articleEhler, J., Petzold, A. Haloperidol is not the "one drug fits all" solution in the treatment of delirium.https://doi.org/10.1186/s13054-025-05413-8Download citationReceived:06 April 2025Accepted:09 April 2025Published: 23 April 2025DOI: https://doi.org/10.1186/s13054-025-05413-8Share 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":"Haloperidol is not the “one drug fits all” solution in the treatment of delirium","authors":"Johannes Ehler, Axel Petzold","doi":"10.1186/s13054-025-05413-8","DOIUrl":"https://doi.org/10.1186/s13054-025-05413-8","url":null,"abstract":"<p>Dear Editor,</p><p>We read with great interest the recent publication by Cheng et al., investigating the role of haloperidol in delirium [1]. We acknowledge the authors’ diligent selection of studies for comparison, but wonder that landmark studies came to a diametrically opposed conclusion [2, 3]. There is need for a balanced interpretation of the presumed meta-analytical benefits of haloperidol regarding survival and delirium duration, with the interpretation of presumably fewer serious adverse events (SAEs) [1,2,3]. There are three key questions on which we would like to learn the authors’ opinion.</p><p>Firstly, the consistent comparison of haloperidol against placebo, while providing a baseline, overlooks the significant evolution towards a multimodal approach in delirium therapy. Current best practices emphasize a holistic strategy integrating non-pharmacological interventions for both prevention and treatment, with pharmacological agents reserved for specific indications [4]. The study does not address the contemporary core delirium care, particularly the extent to which non-pharmacological strategies were implemented. This omission is critical, given the increasing emphasis on non-pharmacological recommendations by leading societies such as the European Society of Anaesthesiology and Intensive Care (ESAIC) [4]. Does focusing solely on pharmacological intervention risks not present an incomplete and potentially biased perspective on delirium management?</p><p>Secondly, the observation of a reduced number of rescue benzodiazepine treatments through application of haloperidol warrants further scrutiny. Do benzodiazepines itself not have a pro-delirogenic potential and are therefore discouraged for treatment of delirium [4]?</p><p>Thirdly, the lack of a significant effect on duration of ventilation raises important questions, particularly concerning the broader context of ICU management. Prolonged ventilation is a multifactorial issue. Does attributing it solely to delirium not overlook the potential influence of sedative medication dosages, paradoxically including haloperidol itself?</p><p>Furthermore, we have concerns regarding the presentation of data in Table 2 on prevention of delirium [1]. The presentation of \"benefits (%)\" might be misleading when the Risk Ratio lacks significance. Similarly, the \"any benefit\" descriptor in Table 1 [1], while highlighting potential advantages, could be misinterpreted as a definitive recommendation for universal haloperidol use. In clinical practice there will be no “one drug fits all solution”.</p><p>In conclusion, we believe that while the study provides valuable data on the efficacy of haloperidol compared to placebo [1], a balanced interpretation should also include:</p><ul>\u0000<li>\u0000<p>Current guidelines increasingly support non-pharmacological strategies as the cornerstone of delirium management [4], moving away from a \"one drug fits all\" approach.</p>\u0000</li>\u0000<li>\u0000<p>Haloperidol carries a risk of QT","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"17 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862747","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 : 2025-04-23DOI: 10.1186/s13054-025-05383-x
Stefanie Vandervelden, Bente Cortens, Steffen Fieuws, Wilma Eegdeman, Stefano Malinverni, Philippe Vanhove, Koen Monsieurs, Jan Breuls, Ives Hubloue, François Stifkens, Jacques Creteur, Lina Wauters, Didier Desruelles
Sepsis and septic shock are associated with high mortality and morbidity despite adequate standard care. Vitamin C deficiency is a common, potentially reversible, contributor to morbidity and mortality in sepsis. Previous studies have shown mixed and conflicting results. Our study aimed to determine the potential benefit of early administration (within 6 h after admission) of vitamin C in patients with sepsis or septic shock. This was a phase 3b prospective, multicenter, double-blinded, randomized placebo-controlled trial. Participants were enrolled in the Emergency Departments of 8 hospitals throughout Belgium. Patients were randomized to receive 1.5 g of vitamin C, or matching placebo, every 6 h for 4 days. The primary outcome was the average post-baseline patient Sequential Organ Failure Assessment (SOFA) score on day 2 to 5. Key secondary outcomes were the maximum SOFA score, 28-day mortality and length of ICU and hospital stay. A total of 300 patients were recruited between June 4th, 2021, and August 19th, 2023. 292 patients, of which 147 were assigned to the vitamin C and 145 to the placebo group, completed the trial and were included in the analysis. The primary outcome (vitamin C, 1.98; placebo, 2.19) was 8.7% lower in the vitamin C group, but not significantly (ratio 0.91, 95% CI 0.77 to 1.08, P = 0.30). In a planned subgroup analysis, patients with a baseline SOFA score of 6 or above had a significant lower average post-baseline SOFA score in the vitamin C group (ratio 0.76, 95% CI 0.86 to 0.99, P = 0.042). Findings were similar in the two groups regarding secondary outcomes and adverse events, except for a lower probability of being on renal replacement therapy in the vitamin C group of the per protocol analysis (ratio 0.28, 95% CI 0.078 to 1.0, P = 0.05). Early treatment with vitamin C did not result in a statistically significant reduction in organ dysfunction. Therefore, this study does not support the use of vitamin C in sepsis patients. Trial registration: ClinicalTrials.gov Identifier: NCT04747795 . Registered 4 February 2021. Question Does early treatment with vitamin C lead to a less severe disease course in patients with sepsis or septic shock? Findings In this randomized clinical trial that included 292 patients, treatment with intravenous vitamin C compared to placebo did not result in a lower average post-baseline patient Sequential Organ Failure Assessment (SOFA) score on day 2 to 5 (1.98 vs 2.19), except for a subgroup of patients with a baseline SOFA score of 6 or above. Meaning Early treatment with vitamin C did not result in a significant improvement of the disease course.
{"title":"Early administration of vitamin C in patients with sepsis or septic shock in emergency departments: a multicenter, double-blind, randomized controlled trial: the C-EASIE trial","authors":"Stefanie Vandervelden, Bente Cortens, Steffen Fieuws, Wilma Eegdeman, Stefano Malinverni, Philippe Vanhove, Koen Monsieurs, Jan Breuls, Ives Hubloue, François Stifkens, Jacques Creteur, Lina Wauters, Didier Desruelles","doi":"10.1186/s13054-025-05383-x","DOIUrl":"https://doi.org/10.1186/s13054-025-05383-x","url":null,"abstract":"Sepsis and septic shock are associated with high mortality and morbidity despite adequate standard care. Vitamin C deficiency is a common, potentially reversible, contributor to morbidity and mortality in sepsis. Previous studies have shown mixed and conflicting results. Our study aimed to determine the potential benefit of early administration (within 6 h after admission) of vitamin C in patients with sepsis or septic shock. This was a phase 3b prospective, multicenter, double-blinded, randomized placebo-controlled trial. Participants were enrolled in the Emergency Departments of 8 hospitals throughout Belgium. Patients were randomized to receive 1.5 g of vitamin C, or matching placebo, every 6 h for 4 days. The primary outcome was the average post-baseline patient Sequential Organ Failure Assessment (SOFA) score on day 2 to 5. Key secondary outcomes were the maximum SOFA score, 28-day mortality and length of ICU and hospital stay. A total of 300 patients were recruited between June 4th, 2021, and August 19th, 2023. 292 patients, of which 147 were assigned to the vitamin C and 145 to the placebo group, completed the trial and were included in the analysis. The primary outcome (vitamin C, 1.98; placebo, 2.19) was 8.7% lower in the vitamin C group, but not significantly (ratio 0.91, 95% CI 0.77 to 1.08, P = 0.30). In a planned subgroup analysis, patients with a baseline SOFA score of 6 or above had a significant lower average post-baseline SOFA score in the vitamin C group (ratio 0.76, 95% CI 0.86 to 0.99, P = 0.042). Findings were similar in the two groups regarding secondary outcomes and adverse events, except for a lower probability of being on renal replacement therapy in the vitamin C group of the per protocol analysis (ratio 0.28, 95% CI 0.078 to 1.0, P = 0.05). Early treatment with vitamin C did not result in a statistically significant reduction in organ dysfunction. Therefore, this study does not support the use of vitamin C in sepsis patients. Trial registration: ClinicalTrials.gov Identifier: NCT04747795 . Registered 4 February 2021. Question Does early treatment with vitamin C lead to a less severe disease course in patients with sepsis or septic shock? Findings In this randomized clinical trial that included 292 patients, treatment with intravenous vitamin C compared to placebo did not result in a lower average post-baseline patient Sequential Organ Failure Assessment (SOFA) score on day 2 to 5 (1.98 vs 2.19), except for a subgroup of patients with a baseline SOFA score of 6 or above. Meaning Early treatment with vitamin C did not result in a significant improvement of the disease course.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"3 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862750","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 : 2025-04-23DOI: 10.1186/s13054-025-05359-x
Rafael Hortêncio Melo, Luciana Gioli-Pereira, Igor Dovorake Lourenço, Rogério Da Hora Passos, Adriana Tumba Bernardo, Giovanni Volpicelli
The clinical presentation of acute pulmonary embolism (PE) can range from mild symptoms to severe shock, circulatory arrest and even death, thereby presenting with a significant high mortality when undiagnosed. Computed tomography pulmonary angiography (CTPA) is the gold-standard imaging modality for diagnosing PE, however, it has several practical limitations and is not widely available in low-income country settings. In this context, point-of-care ultrasound (POCUS) has emerged as a valuable bedside, non-invasive diagnostic tool. This meta-analysis assesses the accuracy of multi-organ POCUS for diagnosing PE in critical care settings. We conducted a systematic search of Pubmed, Embase, Scopus and the Cochrane Library databases for studies comparing multi-organ POCUS with CTPA or ventilation-perfusion scans for PE diagnosis in critical care departments. Two reviewers independently completed search, data abstraction and conducted quality assessment with QUADAS-2 tool. Heterogeneity was examined with I2 statistics. We used a bivariate model of random effects to summarize pooled diagnostic odds ratio (DOR), sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and summary receiver operating characteristic (SROC). Four studies met the inclusion criteria, comprising 594 patients. The mean age of participants ranged from 55.2 to 71 years. Prevalence of PE ranged from 28 to 66.2%. CTPA was the primary reference standard used in most studies. Multi-organ POCUS for PE diagnosis demonstrated a pooled DOR of 25.3 (95% CI 4.43–82.9) with a pooled sensitivity of 0.90 (95% CI 0.85–0.94; I2 = 0%) and specificity of 0.69 (95% CI 0.42–0.87; I2 = 95%). The PLR was 3.35 (95% CI 1.43–8.02) and the NLR was 0.16 (95% CI 0.08–0.32). The SROC curve showed an AUC of 0.89 (95% CI 0.81–0.94). Multi-organ POCUS has high diagnostic accuracy for PE diagnosis in critically ill patients. Further research is needed to validated these findings across different patient populations. CRD42024614328.
{"title":"Diagnostic accuracy of multi-organ point-of-care ultrasound for pulmonary embolism in critically ill patients: a systematic review and meta-analysis","authors":"Rafael Hortêncio Melo, Luciana Gioli-Pereira, Igor Dovorake Lourenço, Rogério Da Hora Passos, Adriana Tumba Bernardo, Giovanni Volpicelli","doi":"10.1186/s13054-025-05359-x","DOIUrl":"https://doi.org/10.1186/s13054-025-05359-x","url":null,"abstract":"The clinical presentation of acute pulmonary embolism (PE) can range from mild symptoms to severe shock, circulatory arrest and even death, thereby presenting with a significant high mortality when undiagnosed. Computed tomography pulmonary angiography (CTPA) is the gold-standard imaging modality for diagnosing PE, however, it has several practical limitations and is not widely available in low-income country settings. In this context, point-of-care ultrasound (POCUS) has emerged as a valuable bedside, non-invasive diagnostic tool. This meta-analysis assesses the accuracy of multi-organ POCUS for diagnosing PE in critical care settings. We conducted a systematic search of Pubmed, Embase, Scopus and the Cochrane Library databases for studies comparing multi-organ POCUS with CTPA or ventilation-perfusion scans for PE diagnosis in critical care departments. Two reviewers independently completed search, data abstraction and conducted quality assessment with QUADAS-2 tool. Heterogeneity was examined with I2 statistics. We used a bivariate model of random effects to summarize pooled diagnostic odds ratio (DOR), sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and summary receiver operating characteristic (SROC). Four studies met the inclusion criteria, comprising 594 patients. The mean age of participants ranged from 55.2 to 71 years. Prevalence of PE ranged from 28 to 66.2%. CTPA was the primary reference standard used in most studies. Multi-organ POCUS for PE diagnosis demonstrated a pooled DOR of 25.3 (95% CI 4.43–82.9) with a pooled sensitivity of 0.90 (95% CI 0.85–0.94; I2 = 0%) and specificity of 0.69 (95% CI 0.42–0.87; I2 = 95%). The PLR was 3.35 (95% CI 1.43–8.02) and the NLR was 0.16 (95% CI 0.08–0.32). The SROC curve showed an AUC of 0.89 (95% CI 0.81–0.94). Multi-organ POCUS has high diagnostic accuracy for PE diagnosis in critically ill patients. Further research is needed to validated these findings across different patient populations. CRD42024614328. ","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"71 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862748","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 : 2025-04-23DOI: 10.1186/s13054-025-05387-7
Nekane Romero-Garcia, Chiara Robba, Berta Monleón, Ana Ruiz-Zarco, Maria Pascual-González, Alberto Ruiz-Pacheco, Felipe Perdomo, Maria Luisa García-Pérez, Ana Mugarra, Laura García, Jose Carbonell, Lavienraj Premraj, Fabio Silvio Taccone, Rafael Badenes
The aim of this study was to evaluate the association of arterial hyperoxemia with neurological outcomes and mortality in adults with acute brain injury (ABI). Six electronic databases, including MEDLINE, Embase and online registers of clinical trials, were systematically searched from inception to June 1 st, 2024. Studies comparing the effects of hyperoxemia versus no hyperoxemia on outcomes of hospitalized adult patients with ABI-related conditions (e.g. traumatic brain injury, post-cardiac arrest, subarachnoid hemorrhage, intracerebral hemorrhage, and ischemic stroke) were included according to PRISMA guidelines. Data were pooled using a random-effects model for unadjusted and covariate-adjusted odds ratios. The primary outcome was poor neurological outcome as defined by each individual study, and the secondary outcome was all-cause mortality. Subgroup analyses were conducted based on principal diagnosis, timing of outcome measures, oxygenation thresholds, among other factors. Meta-regression was applied to identify sources of heterogeneity. After 7,849 nonduplicated records were screened, 66 studies fulfilled eligibility criteria for systematic review. The meta-analysis including 24 studies (16,635 patients) revealed that patients with hyperoxemia are 1.29 times more likely to develop poor neurological outcomes (unadjusted OR, 1.295; 95% Confidence Interval, CI 1.040–1.616) compared with those with no hyperoxemia, particularly in subarachnoid hemorrhage and ischemic stroke subgroups. The meta-analysis including 35 studies (98,207 patients) revealed that all-cause mortality is 1.13 times more likely (OR 1.13; 95% CI 1.002–1.282) in patients with hyperoxemia compared with no hyperoxemia. In our study we found that hyperoxemia is significantly associated with an increased risk of poor neurological outcomes and mortality in patients with acute brain injury compared to those with no hyperoxemia. Our results suggest the importance of carefully adjusting oxygenation strategies in neurocritical ICUs.
{"title":"Neurological outcomes and mortality following hyperoxemia in adult patients with acute brain injury: an updated meta-analysis and meta-regression","authors":"Nekane Romero-Garcia, Chiara Robba, Berta Monleón, Ana Ruiz-Zarco, Maria Pascual-González, Alberto Ruiz-Pacheco, Felipe Perdomo, Maria Luisa García-Pérez, Ana Mugarra, Laura García, Jose Carbonell, Lavienraj Premraj, Fabio Silvio Taccone, Rafael Badenes","doi":"10.1186/s13054-025-05387-7","DOIUrl":"https://doi.org/10.1186/s13054-025-05387-7","url":null,"abstract":"The aim of this study was to evaluate the association of arterial hyperoxemia with neurological outcomes and mortality in adults with acute brain injury (ABI). Six electronic databases, including MEDLINE, Embase and online registers of clinical trials, were systematically searched from inception to June 1 st, 2024. Studies comparing the effects of hyperoxemia versus no hyperoxemia on outcomes of hospitalized adult patients with ABI-related conditions (e.g. traumatic brain injury, post-cardiac arrest, subarachnoid hemorrhage, intracerebral hemorrhage, and ischemic stroke) were included according to PRISMA guidelines. Data were pooled using a random-effects model for unadjusted and covariate-adjusted odds ratios. The primary outcome was poor neurological outcome as defined by each individual study, and the secondary outcome was all-cause mortality. Subgroup analyses were conducted based on principal diagnosis, timing of outcome measures, oxygenation thresholds, among other factors. Meta-regression was applied to identify sources of heterogeneity. After 7,849 nonduplicated records were screened, 66 studies fulfilled eligibility criteria for systematic review. The meta-analysis including 24 studies (16,635 patients) revealed that patients with hyperoxemia are 1.29 times more likely to develop poor neurological outcomes (unadjusted OR, 1.295; 95% Confidence Interval, CI 1.040–1.616) compared with those with no hyperoxemia, particularly in subarachnoid hemorrhage and ischemic stroke subgroups. The meta-analysis including 35 studies (98,207 patients) revealed that all-cause mortality is 1.13 times more likely (OR 1.13; 95% CI 1.002–1.282) in patients with hyperoxemia compared with no hyperoxemia. In our study we found that hyperoxemia is significantly associated with an increased risk of poor neurological outcomes and mortality in patients with acute brain injury compared to those with no hyperoxemia. Our results suggest the importance of carefully adjusting oxygenation strategies in neurocritical ICUs. ","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"6 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862743","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}