Pub Date : 2025-01-01DOI: 10.1016/j.jointm.2024.07.006
Jean-Jacques Rouby , Jing Xia , Jayesh Dhanani , Gianluigi Li Bassi , Antoine Monsel , Antoni Torres
Aminoglycosides are concentration-dependent antibiotics exerting a bactericidal effect when concentrations at the site of infection are equal to or greater than 5 times the minimum inhibitory concentrations (MIC). When administered intravenously, they exhibit poor lung penetration and high systemic renal and ototoxicity, imposing to restrict their administration to 5 days. Experimental studies conducted in anesthetized and mechanically ventilated sheep and pigs provide evidence that high doses of nebulized aminoglycosides induce a rapid and potent bacterial killing in the infected lung parenchyma. They also confirm that the alveolar-capillary membrane, either normal or injured by the infectious process, restricts the penetration of intravenous aminoglycosides in the infected lung parenchyma, precluding a bactericidal effect at the site of infection. However, injury of the alveolar-capillary membrane promotes the systemic diffusion of nebulized aminoglycosides. Based on experimental data obtained in animals with inoculation pneumonia, it challenges the classical belief that nebulization protects against systemic toxicity. Loss of lung aeration decreases the lung penetration of nebulized aminoglycosides. Nevertheless, lung tissue concentrations measured in non-aerated lung regions with severe and extended pneumonia are most often greater than 5 times the MICs, resulting in a bactericidal effect followed by a progressive pulmonary reaeration. It is likely that the penetration into the consolidated lung, results from the bronchial diffusion of nebulized aminoglycosides toward adjacent non-aerated infected alveolar spaces and their penetration into mechanical ventilation-induced intraparenchymal pseudocysts and distended bronchioles. In animals receiving nebulized aminoglycosides, epithelial lining fluid concentrations grossly overestimate lung interstitial fluid concentrations because of the bronchial contamination of the distal tip of the bronchoscope during the bronchoalveolar procedures. Lung microdialysis is the only technique able to accurately assess lung pharmacokinetics in animals with inoculation pneumonia treated by nebulized aminoglycosides. In 2024, the European Investigators Network for Nebulized Antibiotics in Ventilator-associated Pneumonia (ENAVAP) called for the creation of an international research network for Lung Microdialysis applied to Nebulized Antibiotics (LUMINA) to promote multicentered, experimental, randomized, and controlled studies addressing lung pharmacokinetics of intravenous vs. nebulized antibiotics, using different dosing and ventilator settings.
{"title":"Nebulized aminoglycosides for ventilator-associated pneumonia: Methodological considerations and lessons from experimental studies","authors":"Jean-Jacques Rouby , Jing Xia , Jayesh Dhanani , Gianluigi Li Bassi , Antoine Monsel , Antoni Torres","doi":"10.1016/j.jointm.2024.07.006","DOIUrl":"10.1016/j.jointm.2024.07.006","url":null,"abstract":"<div><div>Aminoglycosides are concentration-dependent antibiotics exerting a bactericidal effect when concentrations at the site of infection are equal to or greater than 5 times the minimum inhibitory concentrations (MIC). When administered intravenously, they exhibit poor lung penetration and high systemic renal and ototoxicity, imposing to restrict their administration to 5 days. Experimental studies conducted in anesthetized and mechanically ventilated sheep and pigs provide evidence that high doses of nebulized aminoglycosides induce a rapid and potent bacterial killing in the infected lung parenchyma. They also confirm that the alveolar-capillary membrane, either normal or injured by the infectious process, restricts the penetration of intravenous aminoglycosides in the infected lung parenchyma, precluding a bactericidal effect at the site of infection. However, injury of the alveolar-capillary membrane promotes the systemic diffusion of nebulized aminoglycosides. Based on experimental data obtained in animals with inoculation pneumonia, it challenges the classical belief that nebulization protects against systemic toxicity. Loss of lung aeration decreases the lung penetration of nebulized aminoglycosides. Nevertheless, lung tissue concentrations measured in non-aerated lung regions with severe and extended pneumonia are most often greater than 5 times the MICs, resulting in a bactericidal effect followed by a progressive pulmonary reaeration. It is likely that the penetration into the consolidated lung, results from the bronchial diffusion of nebulized aminoglycosides toward adjacent non-aerated infected alveolar spaces and their penetration into mechanical ventilation-induced intraparenchymal pseudocysts and distended bronchioles. In animals receiving nebulized aminoglycosides, epithelial lining fluid concentrations grossly overestimate lung interstitial fluid concentrations because of the bronchial contamination of the distal tip of the bronchoscope during the bronchoalveolar procedures. Lung microdialysis is the only technique able to accurately assess lung pharmacokinetics in animals with inoculation pneumonia treated by nebulized aminoglycosides. In 2024, the European Investigators Network for Nebulized Antibiotics in Ventilator-associated Pneumonia (ENAVAP) called for the creation of an international research network for Lung Microdialysis applied to Nebulized Antibiotics (LUMINA) to promote multicentered, experimental, randomized, and controlled studies addressing lung pharmacokinetics of intravenous vs. nebulized antibiotics, using different dosing and ventilator settings.</div></div>","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 1","pages":"Pages 12-22"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.jointm.2024.06.003
Xiaomeng Tang , Jingjing Ning , Yilin Zhao , Shuyun Feng , Lujing Shao , Tiantian Liu , Huijie Miao , Yucai Zhang , Chunxia Wang
Background
Cholestasis plays a critical role in sepsis-associated liver injury (SALI). Intestine-derived fibroblast growth factor 19 (FGF19) is a key regulator for bile acid homeostasis. However, the roles and underlying mechanisms of FGF19 in SALI are still unclear.
Methods
We conducted a case–control study that included 58 pediatric patients aged from 1 month to 14-years-old diagnosed with sepsis at Shanghai Children's Hospital from January to December 2018 and 30 healthy individuals. The serum FGF19 levels of these patients with sepsis were analyzed and compared with those of healthy controls. Recombinant human FGF19 was intravenously injected in mice once a day for 7 days at a dose of 0.1 mg/kg body weight before lipopolysaccharide (LPS) treatment. Liver bile acid profiles and the gene expression involved in bile acid homeostasis were investigated in the mice groups. Metabolomic data were further integrated and analyzed using Ingenuity Pathways Analysis (IPA) software. In the in vitro analysis using HepG2 cells, the influence of FGF19 pretreatment on reactive oxygen species (ROS) production and mitochondrial dysfunction was analyzed. Compound C (CC), an inhibitor of AMP-activated protein kinase (AMPK) activation, was used to confirm the roles of AMPK activation in FGF19-mediated hepatoprotective effects.
Results
Serum FGF19 levels were significantly lower in children with sepsis than in healthy controls (115 pg/mL vs. 79 pg/mL, P=0.03). Pre-administration of recombinant human FGF19 alleviated LPS-induced acute liver injury (ALI) and improved LPS-induced cholestasis in mice. Moreover, FGF19 directly reversed LPS-induced intracellular ROS generation and LPS-decreased mitochondrial membrane potential in vitro and in vivo, resulting in hepatoprotection against LPS-induced apoptosis. More importantly, the inhibition of AMPK activity partially blocked the protective effects of FGF19 against LPS-induced oxidative stress and mitochondrial dysfunction.
Conclusions
Intestine-derived FGF19 alleviates LPS-induced ALI via improving bile acid homeostasis and directly suppressing ROS production via activating the AMPK signaling pathway.
{"title":"Intestine-derived fibroblast growth factor 19 alleviates lipopolysaccharide-induced liver injury by regulating bile acid homeostasis and directly improving oxidative stress","authors":"Xiaomeng Tang , Jingjing Ning , Yilin Zhao , Shuyun Feng , Lujing Shao , Tiantian Liu , Huijie Miao , Yucai Zhang , Chunxia Wang","doi":"10.1016/j.jointm.2024.06.003","DOIUrl":"10.1016/j.jointm.2024.06.003","url":null,"abstract":"<div><h3>Background</h3><div>Cholestasis plays a critical role in sepsis-associated liver injury (SALI). Intestine-derived fibroblast growth factor 19 (FGF19) is a key regulator for bile acid homeostasis. However, the roles and underlying mechanisms of FGF19 in SALI are still unclear.</div></div><div><h3>Methods</h3><div>We conducted a case–control study that included 58 pediatric patients aged from 1 month to 14-years-old diagnosed with sepsis at Shanghai Children's Hospital from January to December 2018 and 30 healthy individuals. The serum FGF19 levels of these patients with sepsis were analyzed and compared with those of healthy controls. Recombinant human FGF19 was intravenously injected in mice once a day for 7 days at a dose of 0.1 mg/kg body weight before lipopolysaccharide (LPS) treatment. Liver bile acid profiles and the gene expression involved in bile acid homeostasis were investigated in the mice groups. Metabolomic data were further integrated and analyzed using Ingenuity Pathways Analysis (IPA) software. In the <em>in vitro</em> analysis using HepG2 cells, the influence of FGF19 pretreatment on reactive oxygen species (ROS) production and mitochondrial dysfunction was analyzed. Compound C (CC), an inhibitor of AMP-activated protein kinase (AMPK) activation, was used to confirm the roles of AMPK activation in FGF19-mediated hepatoprotective effects.</div></div><div><h3>Results</h3><div>Serum FGF19 levels were significantly lower in children with sepsis than in healthy controls (115 pg/mL <em>vs</em>. 79 pg/mL, <em>P</em>=0.03). Pre-administration of recombinant human FGF19 alleviated LPS-induced acute liver injury (ALI) and improved LPS-induced cholestasis in mice. Moreover, FGF19 directly reversed LPS-induced intracellular ROS generation and LPS-decreased mitochondrial membrane potential <em>in vitro</em> and <em>in vivo</em>, resulting in hepatoprotection against LPS-induced apoptosis. More importantly, the inhibition of AMPK activity partially blocked the protective effects of FGF19 against LPS-induced oxidative stress and mitochondrial dysfunction.</div></div><div><h3>Conclusions</h3><div>Intestine-derived FGF19 alleviates LPS-induced ALI via improving bile acid homeostasis and directly suppressing ROS production via activating the AMPK signaling pathway.</div></div>","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 1","pages":"Pages 79-88"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-24DOI: 10.1016/j.jointm.2024.12.001
Laurens A. Biesheuvel , Jessica D. Workum , Merijn Reuland , Michel E. van Genderen , Patrick Thoral , Dave Dongelmans , Paul Elbers
The advent of chat generative pre-trained transformer (ChatGPT) and large language models (LLMs) has revolutionized natural language processing (NLP). These models possess unprecedented capabilities in understanding and generating human-like language. This breakthrough holds significant promise for critical care medicine, where unstructured data and complex clinical information are abundant. Key applications of LLMs in this field include administrative support through automated documentation and patient chart summarization; clinical decision support by assisting in diagnostics and treatment planning; personalized communication to enhance patient and family understanding; and improving data quality by extracting insights from unstructured clinical notes. Despite these opportunities, challenges such as the risk of generating inaccurate or biased information “hallucinations”, ethical considerations, and the need for clinician artificial intelligence (AI) literacy must be addressed. Integrating LLMs with traditional machine learning models – an approach known as Hybrid AI – combines the strengths of both technologies while mitigating their limitations. Careful implementation, regulatory compliance, and ongoing validation are essential to ensure that LLMs enhance patient care rather than hinder it. LLMs have the potential to transform critical care practices, but integrating them requires caution. Responsible use and thorough clinician training are crucial to fully realize their benefits.
{"title":"Large language models in critical care","authors":"Laurens A. Biesheuvel , Jessica D. Workum , Merijn Reuland , Michel E. van Genderen , Patrick Thoral , Dave Dongelmans , Paul Elbers","doi":"10.1016/j.jointm.2024.12.001","DOIUrl":"10.1016/j.jointm.2024.12.001","url":null,"abstract":"<div><div>The advent of chat generative pre-trained transformer (ChatGPT) and large language models (LLMs) has revolutionized natural language processing (NLP). These models possess unprecedented capabilities in understanding and generating human-like language. This breakthrough holds significant promise for critical care medicine, where unstructured data and complex clinical information are abundant. Key applications of LLMs in this field include administrative support through automated documentation and patient chart summarization; clinical decision support by assisting in diagnostics and treatment planning; personalized communication to enhance patient and family understanding; and improving data quality by extracting insights from unstructured clinical notes. Despite these opportunities, challenges such as the risk of generating inaccurate or biased information “hallucinations”, ethical considerations, and the need for clinician artificial intelligence (AI) literacy must be addressed. Integrating LLMs with traditional machine learning models – an approach known as Hybrid AI – combines the strengths of both technologies while mitigating their limitations. Careful implementation, regulatory compliance, and ongoing validation are essential to ensure that LLMs enhance patient care rather than hinder it. LLMs have the potential to transform critical care practices, but integrating them requires caution. Responsible use and thorough clinician training are crucial to fully realize their benefits.</div></div>","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 2","pages":"Pages 113-118"},"PeriodicalIF":0.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-19DOI: 10.1016/j.jointm.2024.10.005
Nicolás Colaianni-Alfonso , Federico Herrera , Diego Flores , Cristian Deana , Mina Vapireva , Daniele Guerino Biasucci , Salvatore Maurizio Maggiore , Luigi Vetrugno
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. During severe exacerbations, COPD patients may develop acute respiratory failure (ARF), often necessitating hospital admission due to impaired gas exchange. In COPD patients, the diaphragm is subjected to an increased workload resulting from airflow limitations and geometric changes in the thorax due to pulmonary hyperinflation. Noninvasive ventilation (NIV) plays a crucial role in managing type II ARF by improving alveolar ventilation, reducing the work of breathing, minimizing the need for endotracheal intubation (ETI), and decreasing both hospital stays and mortality rates. Studies have shown that approximately 64% of patients with acute exacerbation of COPD (AECOPD) may fail NIV, primarily due to worsening respiratory function, interface intolerance, cardiovascular instability, or neurological deterioration. For patients intolerant to NIV, a trial with a high-flow nasal cannula (HFNC) is recommended. Recently, HFNC has gained popularity as a novel respiratory support system and is increasingly used in routine clinical practice for AECOPD patients. It delivers warmed, humidified, and oxygen-enriched air through a nasal cannula at flow rates of up to 60 L/min. This narrative review aims to describe the physiological effects of HFNC in the COPD population and provide an updated overview of HFNC's role in AECOPD patients requiring hospitalization.
{"title":"Physiological effects and clinical evidence of high-flow nasal cannula during acute exacerbation in COPD patients: A narrative review","authors":"Nicolás Colaianni-Alfonso , Federico Herrera , Diego Flores , Cristian Deana , Mina Vapireva , Daniele Guerino Biasucci , Salvatore Maurizio Maggiore , Luigi Vetrugno","doi":"10.1016/j.jointm.2024.10.005","DOIUrl":"10.1016/j.jointm.2024.10.005","url":null,"abstract":"<div><div>Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. During severe exacerbations, COPD patients may develop acute respiratory failure (ARF), often necessitating hospital admission due to impaired gas exchange. In COPD patients, the diaphragm is subjected to an increased workload resulting from airflow limitations and geometric changes in the thorax due to pulmonary hyperinflation. Noninvasive ventilation (NIV) plays a crucial role in managing type II ARF by improving alveolar ventilation, reducing the work of breathing, minimizing the need for endotracheal intubation (ETI), and decreasing both hospital stays and mortality rates. Studies have shown that approximately 64% of patients with acute exacerbation of COPD (AECOPD) may fail NIV, primarily due to worsening respiratory function, interface intolerance, cardiovascular instability, or neurological deterioration. For patients intolerant to NIV, a trial with a high-flow nasal cannula (HFNC) is recommended. Recently, HFNC has gained popularity as a novel respiratory support system and is increasingly used in routine clinical practice for AECOPD patients. It delivers warmed, humidified, and oxygen-enriched air through a nasal cannula at flow rates of up to 60 L/min. This narrative review aims to describe the physiological effects of HFNC in the COPD population and provide an updated overview of HFNC's role in AECOPD patients requiring hospitalization.</div></div>","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 2","pages":"Pages 127-133"},"PeriodicalIF":0.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-18DOI: 10.1016/j.jointm.2024.11.002
Hasan Abualruz , Mohammad A. Abu Sabra , Elham H. Othman , Malakeh Z. Malak , Saleh Al Omar , Reema R. Safadi , Salah M. AbuRuz , Khaled Suleiman
Background
Family presence during resuscitation (FPDR) is a controversial issue that remains unresolved in contemporary practice. Although there are many research studies on FPDR and several published statements and guidelines supporting FPDR by international organizations, no conclusive position guides clinicians in making a decision. A scoping review was conducted to discuss the different healthcare professionals (HCPs) and cultural perspectives toward family presence during CPR is conducted.
Methods
Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines, we screened 797 studies published between 2000 and 2022 from the databases including Springer Link, MEDLINE, Pro-Quest Central, CINAHL Plus, and Google Scholar. All articles were filtered using inclusion criteria to eliminate redundant, irrelevant, and unnecessary content.
Results
A total of 34 studies that fulfill the eligibility criteria reported that there are multiple perspectives from HCPs and families about FPDR. HCPs felt that their performance had improved during resuscitation and received family support in breaking the bad news of death. Family relatives who attended cardiopulmonary resuscitation (CPR) had less stress, less anxiety, more positive grieving behavior, and enhanced family members’ decision-making. Contrastingly, some HCPs were against FPDR because they were concerned about the family's misinterpretation of resuscitation activities, psychological trauma to the family members, increased stress levels among staff, and worry about an unexpected response from the distressed family.
Conclusions
It is important to consider the culture and awareness of families when deciding on FPDR. It is the responsibility of HCPs to assess family members’ willingness and the benefits they attain from attending CPR. The decision should be based on the given situation, cultural context and beliefs, and current policy to guide practice.
{"title":"Is it beneficial to allow the patient's family to attend cardiac resuscitation: Different cultural perspectives? A scoping review","authors":"Hasan Abualruz , Mohammad A. Abu Sabra , Elham H. Othman , Malakeh Z. Malak , Saleh Al Omar , Reema R. Safadi , Salah M. AbuRuz , Khaled Suleiman","doi":"10.1016/j.jointm.2024.11.002","DOIUrl":"10.1016/j.jointm.2024.11.002","url":null,"abstract":"<div><h3>Background</h3><div>Family presence during resuscitation (FPDR) is a controversial issue that remains unresolved in contemporary practice. Although there are many research studies on FPDR and several published statements and guidelines supporting FPDR by international organizations, no conclusive position guides clinicians in making a decision. A scoping review was conducted to discuss the different healthcare professionals (HCPs) and cultural perspectives toward family presence during CPR is conducted.</div></div><div><h3>Methods</h3><div>Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines, we screened 797 studies published between 2000 and 2022 from the databases including Springer Link, MEDLINE, Pro-Quest Central, CINAHL Plus, and Google Scholar. All articles were filtered using inclusion criteria to eliminate redundant, irrelevant, and unnecessary content.</div></div><div><h3>Results</h3><div>A total of 34 studies that fulfill the eligibility criteria reported that there are multiple perspectives from HCPs and families about FPDR. HCPs felt that their performance had improved during resuscitation and received family support in breaking the bad news of death. Family relatives who attended cardiopulmonary resuscitation (CPR) had less stress, less anxiety, more positive grieving behavior, and enhanced family members’ decision-making. Contrastingly, some HCPs were against FPDR because they were concerned about the family's misinterpretation of resuscitation activities, psychological trauma to the family members, increased stress levels among staff, and worry about an unexpected response from the distressed family.</div></div><div><h3>Conclusions</h3><div>It is important to consider the culture and awareness of families when deciding on FPDR. It is the responsibility of HCPs to assess family members’ willingness and the benefits they attain from attending CPR. The decision should be based on the given situation, cultural context and beliefs, and current policy to guide practice.</div></div>","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 2","pages":"Pages 202-210"},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-10DOI: 10.1016/j.jointm.2024.10.004
Xiaofeng Wang , Yiwen Qiu , Ying Di , Hou Shaohua , Wei Wu , Weiyi Wang , Huan Liu , Pu Li
Background
Acute pancreatitis (AP) ranks among the most frequently encountered gastrointestinal diseases in the emergency department. Recent studies have increasingly emphasized the substantial connection among gut microbiota, inflammatory cytokines, and AP.
Methods
A two-sample Mendelian randomization (MR) study was conducted using summary statistics of gut microbiota (GM) from the largest available meta-analysis of genome-wide association studies conducted by the MiBioGen consortium (n=18,340). For cytokines, the data were obtained from a study that investigated genome variant associations with 41 inflammatory cytokines and growth factors (n=8293). The summary statistics of AP were obtained from the FinnGen consortium version R5 data (3022 cases and 195,144 controls). The inverse variance weighted (IVW) method was used as the main analysis, with MR–Egger and weighted median as complementary analytical methods. Sensitivity analyses were performed using Cochran's Q-test, MR–Egger intercept test, leave-one-out analyses, and MR–PRESSO. In addition, we employed the reverse MR analysis and MR Steiger method to estimate the orientations of exposure and outcome.
Result
Among the 211 examined GM taxa, the IVW method revealed that Bacteroidales (odds ratio [OR]=1.412, 95% confidence interval [CI]:1.057 to 1.885, P=0.019), Eubacterium fissicatena group (OR=1.240, 95% CI:1.045 to 1.470, P=0.014), and Coprococcus3 (OR=1.481, 95 % CI:1.049 to 2.090, P=0.026) exhibited a positive association with AP. Conversely, Prevotella9 (OR=0.821, 95% CI:0.680 to 0.990, P=0.038), RuminococcaceaeUCG004 (OR=0.757, 95% CI:0.577 to 0.994, P=0.045), and Ruminiclostridium6 (OR=0.696, 95% CI:0.548 to 0.884, P=0.003) displayed a negative correlation with AP. Among the 41 inflammatory cytokines, only macrophage colony-stimulating factor (M_CSF, OR=0.894, 95% CI:0.847 to 0.943, P=0.037) exhibited a negative association with AP. Sensitivity analyses revealed no evidence of pleiotropy or heterogeneity. Nevertheless, the mediation analysis showed that M_CSF did not act as a mediating factor.
Conclusion
This two-sample MR study revealed causal associations between specific GM and inflammatory cytokines with AP, respectively. However, inflammatory cytokines did not appear to act as mediating factors in the pathway from GM to AP.
{"title":"Potential causal association between gut microbiota, inflammatory cytokines, and acute pancreatitis: A Mendelian randomization study","authors":"Xiaofeng Wang , Yiwen Qiu , Ying Di , Hou Shaohua , Wei Wu , Weiyi Wang , Huan Liu , Pu Li","doi":"10.1016/j.jointm.2024.10.004","DOIUrl":"10.1016/j.jointm.2024.10.004","url":null,"abstract":"<div><h3>Background</h3><div>Acute pancreatitis (AP) ranks among the most frequently encountered gastrointestinal diseases in the emergency department. Recent studies have increasingly emphasized the substantial connection among gut microbiota, inflammatory cytokines, and AP.</div></div><div><h3>Methods</h3><div>A two-sample Mendelian randomization (MR) study was conducted using summary statistics of gut microbiota (GM) from the largest available meta-analysis of genome-wide association studies conducted by the MiBioGen consortium (<em>n</em>=18,340). For cytokines, the data were obtained from a study that investigated genome variant associations with 41 inflammatory cytokines and growth factors (<em>n</em>=8293). The summary statistics of AP were obtained from the FinnGen consortium version R5 data (3022 cases and 195,144 controls). The inverse variance weighted (IVW) method was used as the main analysis, with MR–Egger and weighted median as complementary analytical methods. Sensitivity analyses were performed using Cochran's <em>Q</em>-test, MR–Egger intercept test, leave-one-out analyses, and MR–PRESSO. In addition, we employed the reverse MR analysis and MR Steiger method to estimate the orientations of exposure and outcome.</div></div><div><h3>Result</h3><div>Among the 211 examined GM taxa, the IVW method revealed that Bacteroidales (odds ratio [OR]=1.412, 95% confidence interval [CI]:1.057 to 1.885, <em>P</em>=0.019), <em>Eubacterium fissicatena</em> group (OR=1.240, 95% CI:1.045 to 1.470, <em>P</em>=0.014), and Coprococcus3 (OR=1.481, 95 % CI:1.049 to 2.090, <em>P</em>=0.026) exhibited a positive association with AP. Conversely, Prevotella9 (OR=0.821, 95% CI:0.680 to 0.990, <em>P</em>=0.038), RuminococcaceaeUCG004 (OR=0.757, 95% CI:0.577 to 0.994, <em>P</em>=0.045), and Ruminiclostridium6 (OR=0.696, 95% CI:0.548 to 0.884, <em>P</em>=0.003) displayed a negative correlation with AP. Among the 41 inflammatory cytokines, only macrophage colony-stimulating factor (M_CSF, OR=0.894, 95% CI:0.847 to 0.943, <em>P</em>=0.037) exhibited a negative association with AP. Sensitivity analyses revealed no evidence of pleiotropy or heterogeneity. Nevertheless, the mediation analysis showed that M_CSF did not act as a mediating factor.</div></div><div><h3>Conclusion</h3><div>This two-sample MR study revealed causal associations between specific GM and inflammatory cytokines with AP, respectively. However, inflammatory cytokines did not appear to act as mediating factors in the pathway from GM to AP.</div></div>","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 2","pages":"Pages 185-192"},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-30DOI: 10.1016/j.jointm.2024.10.003
Lada Lijović , Harm Jan de Grooth , Patrick Thoral , Lieuwe Bos , Zheng Feng , Tomislav Radočaj , Paul Elbers
Background
Manual data abstraction from electronic health records (EHRs) for research on intensive care patients is time-intensive and challenging, especially during high-pressure periods such as pandemics. Automated data extraction is a potential alternative but may raise quality concerns. This study assessed the feasibility and credibility of automated data extraction during the coronavirus disease 2019 (COVID-19) pandemic.
Methods
We retrieved routinely collected data from the COVID-Predict Dutch Data Warehouse, a multicenter database containing the following data on intensive care patients with COVID-19: demographic, medication, laboratory results, and data from monitoring and life support devices. These data were sourced from EHRs using automated data extraction. We used these data to determine indices of wasted ventilation and their prognostic value and compared our findings to a previously published original study that relied on manual data abstraction largely from the same hospitals.
Results
Using automatically extracted data, we replicated the original study. Among 1515 patients intubated for over 2 days, Harris–Benedict (HB) estimates of dead space fraction increased over time and were higher in non-survivors at each time point: at the start of ventilation (0.70±0.13 vs. 0.67±0.15, P <0.001), day 1 (0.74±0.10 vs. 0.71±0.11, P<0.001), day 2 (0.77±0.09 vs. 0.73±0.11, P<0.001), and day 3 (0.78±0.09 vs. 0.74±0.10, P<0.001). Patients with HB dead space fraction above the median had an increased mortality rate of 13.5%, compared to 10.1% in those with values below the median (P<0.005). Ventilatory ratio showed similar trends, with mortality increasing from 10.8% to 12.9% (P=0.040). Conversely, the end-tidal-to-arterial partial pressure of carbon dioxide (PaCO₂) ratio was inversely related to mortality, with a lower 28-day mortality in the higher than median group (8.5% vs. 15.1%, P<0.001). After adjusting for base risk, impaired ventilation markers showed no significant association with 28-day mortality.
Conclusion
Manual data abstraction from EHRs may be unnecessary for reliable research on intensive care patients, highlighting the feasibility and credibility of automated data extraction as a trustworthy and scalable solution to accelerate clinical insights, especially during future pandemics.
{"title":"Preparing for future pandemics: Automated intensive care electronic health record data extraction to accelerate clinical insights","authors":"Lada Lijović , Harm Jan de Grooth , Patrick Thoral , Lieuwe Bos , Zheng Feng , Tomislav Radočaj , Paul Elbers","doi":"10.1016/j.jointm.2024.10.003","DOIUrl":"10.1016/j.jointm.2024.10.003","url":null,"abstract":"<div><h3>Background</h3><div>Manual data abstraction from electronic health records (EHRs) for research on intensive care patients is time-intensive and challenging, especially during high-pressure periods such as pandemics. Automated data extraction is a potential alternative but may raise quality concerns. This study assessed the feasibility and credibility of automated data extraction during the coronavirus disease 2019 (COVID-19) pandemic.</div></div><div><h3>Methods</h3><div>We retrieved routinely collected data from the COVID-Predict Dutch Data Warehouse, a multicenter database containing the following data on intensive care patients with COVID-19: demographic, medication, laboratory results, and data from monitoring and life support devices. These data were sourced from EHRs using automated data extraction. We used these data to determine indices of wasted ventilation and their prognostic value and compared our findings to a previously published original study that relied on manual data abstraction largely from the same hospitals.</div></div><div><h3>Results</h3><div>Using automatically extracted data, we replicated the original study. Among 1515 patients intubated for over 2 days, Harris–Benedict (HB) estimates of dead space fraction increased over time and were higher in non-survivors at each time point: at the start of ventilation (0.70±0.13 <em>vs</em>. 0.67±0.15, <em>P</em> <0.001), day 1 (0.74±0.10 <em>vs</em>. 0.71±0.11, <em>P</em><0.001), day 2 (0.77±0.09 <em>vs</em>. 0.73±0.11, <em>P</em><0.001), and day 3 (0.78±0.09 <em>vs</em>. 0.74±0.10, <em>P</em><0.001). Patients with HB dead space fraction above the median had an increased mortality rate of 13.5%, compared to 10.1% in those with values below the median (<em>P</em><0.005). Ventilatory ratio showed similar trends, with mortality increasing from 10.8% to 12.9% (<em>P</em>=0.040). Conversely, the end-tidal-to-arterial partial pressure of carbon dioxide (PaCO₂) ratio was inversely related to mortality, with a lower 28-day mortality in the higher than median group (8.5% <em>vs</em>. 15.1%, <em>P</em><0.001). After adjusting for base risk, impaired ventilation markers showed no significant association with 28-day mortality.</div></div><div><h3>Conclusion</h3><div>Manual data abstraction from EHRs may be unnecessary for reliable research on intensive care patients, highlighting the feasibility and credibility of automated data extraction as a trustworthy and scalable solution to accelerate clinical insights, especially during future pandemics.</div></div>","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 2","pages":"Pages 167-175"},"PeriodicalIF":0.0,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sepsis and septic shock are major healthcare problems worldwide, associated with substantial mortality. Early administration of norepinephrine in septic shock patients has been associated with an increased survival rate, but the timing from septic shock to norepinephrine initiation is controversial. This study examined the associations between the timing of initial norepinephrine administration and clinical outcomes in adult patients with septic shock.
Methods
This prospective cohort study was conducted from September 2021 to June 2022 in an intensive care unit (ICU) of a tertiary general hospital. All enrolled patients were divided into early and late norepinephrine groups according to whether the time from the onset of septic shock to the first application of norepinephrine was >1 h. The primary outcome was 28-day mortality. Secondary outcomes included ICU length of stay (LOS), hospital LOS, time to achieve a mean arterial pressure (MAP) ≥65 mmHg, 24-hour infusion volume, 6-hour Lac clearance, mechanical ventilation days, and continuous renal replacement therapy (CRRT )ratio. Multivariable logistic regression analysis was used to evaluate the independent risk factors for 28-day mortality.
Results
This study enrolled 120 patients, including 42 patients (35.0%) and 78 patients (65.0%) in the early and late norepinephrine groups, respectively. The 28-day mortality was lower in the early group than in the late group (28.6% vs. 47.4%, P=0.045). The median time to achieve MAP ≥65 mmHg was shorter in the early group than in the late group (1.0 h vs. 1.5 h, P=0.010). The median 24-hour intravenous fluids volume in the early group was lower than that in the late group (40.7% vs. 14.9%, P=0.030). The median 6-hour lactate (Lac) clearance rate in the early group was higher than that in the late group (40.7% vs. 14.9%, P=0.009). There were no significant differences between early and late groups by ICU LOS (P=0.748), hospital LOS (P=0.369), mechanical ventilation time (P=0.128), and CRRT ratio (P=0.637). The independent risk factors for 28-day mortality included being male (odds ratio [OR]=3.288, 95% confidence interval [CI]: 1.236 to 8.745, P = 0.017), time to norepinephrine initiation >1 h (OR=4.564, 95% CI: 1.382 to 15.079, P = 0.013), and time to achieve MAP ≥65 mmHg (OR=1.800, 95% CI: 1.171 to 2.767, P = 0.007).
Conclusions
Norepinephrine initiation ≤1 h is associated with lower 28-day mortality in patients with septic shock. Early norepinephrine administration is also associated with a shorter time to achieve MAP ≥65 mmHg, lower 24-hour intravenous fluids volume, and higher 6-hour Lac clearance rate. Being male, time to achieve MAP ≥65 mmHg, and norepinephrine initiation >1 h are independent ris
脓毒症和脓毒性休克是世界范围内的主要卫生保健问题，与大量死亡率相关。脓毒性休克患者早期给予去甲肾上腺素可提高生存率，但脓毒性休克到开始使用去甲肾上腺素的时间存在争议。本研究探讨了成人脓毒性休克患者初始去甲肾上腺素给药时间与临床结果之间的关系。方法本前瞻性队列研究于2021年9月至2022年6月在某三级综合医院重症监护病房（ICU）进行。根据脓毒性休克发生至首次应用去甲肾上腺素的时间是否为1 h，将所有入组患者分为早期和晚期去甲肾上腺素组。主要终点为28天死亡率。次要结局包括ICU住院时间（LOS）、医院LOS、达到平均动脉压(MAP)≥65 mmHg的时间、24小时输注量、6小时Lac清除率、机械通气天数和持续肾脏替代治疗（CRRT）比率。采用多变量logistic回归分析评价28天死亡率的独立危险因素。结果本研究共纳入120例患者，其中去甲肾上腺素早期组42例（占35.0%），晚期组78例（占65.0%）。早期组28天死亡率低于晚期组（28.6%比47.4%，P=0.045）。早期组达到MAP≥65 mmHg的中位时间短于晚期组（1.0 h比1.5 h， P=0.010）。早期组24小时静脉内液量中位数低于晚期组（40.7%比14.9%，P=0.030）。早期组6小时乳酸清除率中位数高于晚期组（40.7% vs. 14.9%， P=0.009）。ICU LOS （P=0.748）、医院LOS （P=0.369）、机械通气时间（P=0.128）、CRRT比值（P=0.637）早、晚两组比较差异均无统计学意义。28天死亡率的独立危险因素包括男性（优势比[OR]=3.288, 95%可信区间[CI]: 1.236 ~ 8.745, P = 0.017）、开始使用去甲肾上腺素1小时的时间（OR=4.564, 95% CI: 1.382 ~ 15.079, P = 0.013）、达到MAP≥65 mmHg的时间（OR=1.800, 95% CI: 1.171 ~ 2.767, P = 0.007）。结论甲肾上腺素起始≤1 h与感染性休克患者28天死亡率降低相关。早期给药去甲肾上腺素也与达到MAP≥65 mmHg所需时间较短、24小时静脉输液量较低和6小时Lac清除率较高相关。男性，达到MAP≥65 mmHg的时间和去甲肾上腺素起始时间1 h是28天死亡率的独立危险因素。中国临床试验注册号：ChiCTR2100044071。
{"title":"Effect of timing of norepinephrine administration on prognosis of patients with septic shock: A prospective cohort study","authors":"Yuting Li, Deyou Zhang, Hongxiang Li, Youquan Wang, Dong Zhang","doi":"10.1016/j.jointm.2024.10.002","DOIUrl":"10.1016/j.jointm.2024.10.002","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis and septic shock are major healthcare problems worldwide, associated with substantial mortality. Early administration of norepinephrine in septic shock patients has been associated with an increased survival rate, but the timing from septic shock to norepinephrine initiation is controversial. This study examined the associations between the timing of initial norepinephrine administration and clinical outcomes in adult patients with septic shock.</div></div><div><h3>Methods</h3><div>This prospective cohort study was conducted from September 2021 to June 2022 in an intensive care unit (ICU) of a tertiary general hospital. All enrolled patients were divided into early and late norepinephrine groups according to whether the time from the onset of septic shock to the first application of norepinephrine was >1 h. The primary outcome was 28-day mortality. Secondary outcomes included ICU length of stay (LOS), hospital LOS, time to achieve a mean arterial pressure (MAP) ≥65 mmHg, 24-hour infusion volume, 6-hour Lac clearance, mechanical ventilation days, and continuous renal replacement therapy (CRRT )ratio. Multivariable logistic regression analysis was used to evaluate the independent risk factors for 28-day mortality.</div></div><div><h3>Results</h3><div>This study enrolled 120 patients, including 42 patients (35.0%) and 78 patients (65.0%) in the early and late norepinephrine groups, respectively. The 28-day mortality was lower in the early group than in the late group (28.6% <em>vs.</em> 47.4%, <em>P</em>=0.045). The median time to achieve MAP ≥65 mmHg was shorter in the early group than in the late group (1.0 h <em>vs.</em> 1.5 h, <em>P</em>=0.010). The median 24-hour intravenous fluids volume in the early group was lower than that in the late group (40.7% <em>vs.</em> 14.9%, <em>P</em>=0.030). The median 6-hour lactate (Lac) clearance rate in the early group was higher than that in the late group (40.7% <em>vs.</em> 14.9%, <em>P</em>=0.009). There were no significant differences between early and late groups by ICU LOS (<em>P</em>=0.748), hospital LOS (<em>P</em>=0.369), mechanical ventilation time (<em>P</em>=0.128), and CRRT ratio (<em>P</em>=0.637). The independent risk factors for 28-day mortality included being male (odds ratio [OR]=3.288, 95% confidence interval [CI]: 1.236 to 8.745, <em>P</em> = 0.017), time to norepinephrine initiation >1 h (OR=4.564, 95% CI: 1.382 to 15.079, <em>P</em> = 0.013), and time to achieve MAP ≥65 mmHg (OR=1.800, 95% CI: 1.171 to 2.767, <em>P</em> = 0.007).</div></div><div><h3>Conclusions</h3><div>Norepinephrine initiation ≤1 h is associated with lower 28-day mortality in patients with septic shock. Early norepinephrine administration is also associated with a shorter time to achieve MAP ≥65 mmHg, lower 24-hour intravenous fluids volume, and higher 6-hour Lac clearance rate. Being male, time to achieve MAP ≥65 mmHg, and norepinephrine initiation >1 h are independent ris","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 2","pages":"Pages 160-166"},"PeriodicalIF":0.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-12DOI: 10.1016/j.jointm.2024.09.002
Zhongheng Zhang , Hongying Ni
The integration of large language models (LLMs) in clinical medicine, particularly in critical care, has introduced transformative capabilities for analyzing and managing complex medical information. This technical note explores the application of LLMs, such as generative pretrained transformer 4 (GPT-4) and Qwen-Chat, in interpreting electronic healthcare records to assist with rapid patient condition assessments, predict sepsis, and automate the generation of discharge summaries. The note emphasizes the significance of LLMs in processing unstructured data from electronic health records (EHRs), extracting meaningful insights, and supporting personalized medicine through nuanced understanding of patient histories. Despite the technical complexity of deploying LLMs in clinical settings, this document provides a comprehensive guide to facilitate the effective integration of LLMs into clinical workflows, focusing on the use of DashScope's application programming interface (API) services for judgment on patient prognosis and organ support recommendations based on natural language in EHRs. By illustrating practical steps and best practices, this work aims to lower the technical barriers for clinicians and researchers, enabling broader adoption of LLMs in clinical research and practice to enhance patient care and outcomes.
{"title":"Critical care studies using large language models based on electronic healthcare records: A technical note","authors":"Zhongheng Zhang , Hongying Ni","doi":"10.1016/j.jointm.2024.09.002","DOIUrl":"10.1016/j.jointm.2024.09.002","url":null,"abstract":"<div><div>The integration of large language models (LLMs) in clinical medicine, particularly in critical care, has introduced transformative capabilities for analyzing and managing complex medical information. This technical note explores the application of LLMs, such as generative pretrained transformer 4 (GPT-4) and Qwen-Chat, in interpreting electronic healthcare records to assist with rapid patient condition assessments, predict sepsis, and automate the generation of discharge summaries. The note emphasizes the significance of LLMs in processing unstructured data from electronic health records (EHRs), extracting meaningful insights, and supporting personalized medicine through nuanced understanding of patient histories. Despite the technical complexity of deploying LLMs in clinical settings, this document provides a comprehensive guide to facilitate the effective integration of LLMs into clinical workflows, focusing on the use of DashScope's application programming interface (API) services for judgment on patient prognosis and organ support recommendations based on natural language in EHRs. By illustrating practical steps and best practices, this work aims to lower the technical barriers for clinicians and researchers, enabling broader adoption of LLMs in clinical research and practice to enhance patient care and outcomes.</div></div>","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 2","pages":"Pages 137-150"},"PeriodicalIF":0.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-12DOI: 10.1016/j.jointm.2024.08.003
Max Melchers , Hanneke Pierre Franciscus Xaverius Moonen , Tessa Maria Breeman , Sjoerd Hendrika Willem van Bree , Arthur Raymond Hubert van Zanten
Background
Hypocalcemia is common among patients admitted to the intensive care unit (ICU). The administration of calcium in critically ill patients with hypocalcemia remains debated, as previous data on outcomes are conflicting, and subgroup analyses are lacking. This study aimed to investigate the association between parenteral calcium administration and clinical outcomes in critically ill patients who had hypocalcemia with and without sepsis.
Methods
This retrospective cohort study included individuals who developed hypocalcemia during the first 7 days of admission to a mixed medical-surgical adult ICU at a University-affiliated teaching hospital. Patients who were not receiving renal replacement therapy, and were admitted to the ICU for at least 48 h between October 1, 2015 and September 24, 2020, were included. The primary outcomes included all-cause 180-day mortality and time-to-shock resolution. Subgroup analyses were conducted in sepsis and nonsepsis patients with mild or moderate hypocalcemia, based on median splits. Proportional hazard regression analyses were performed to identify the association between parenteral calcium administration and outcome parameters.
Results
Among the 1100 patients who met the inclusion criteria, 427 (38.8 %) patients were admitted for sepsis and 576 (52.4 %) patients received parenteral calcium. Patients who received and did not receive parenteral calcium demonstrated no significant difference in 180-day mortality (adjusted hazard ratio [aHR] = 1.18, 95 % confidence interval [CI]: 0.90 to 1.56). Intravenous calcium administration reduced the probability of a shorter time to shock resolution (adjusted odds ratio = 0.81, 95 % CI: 0.70 to 0.94). Subgroup analyses in patients with and without sepsis indicated no significant association between calcium administration (aHR = 1.63, 95 % CI: 0.99 to 2.69) and 180-day mortality (aHR = 1.06, 95 % CI: 0.74 to 1.51). Notably, parenteral calcium was associated with an elevated risk of 90- and 180-day mortality in patients who had sepsis and mild hypocalcemia (aHR = 1.88, 95 % CI: 1.02 to 3.47 and aHR = 1.79, 95 % CI: 1.07 to 3.00, respectively).
Conclusions
Intravenous calcium administration did not provide survival or shock resolution benefits in ICU patients with hypocalcemia, and may even be harmful. Further research, including randomized controlled trials, are needed to confirm these findings.
{"title":"Parenteral calcium administration and outcomes in critically ill patients with hypocalcemia: A retrospective cohort study","authors":"Max Melchers , Hanneke Pierre Franciscus Xaverius Moonen , Tessa Maria Breeman , Sjoerd Hendrika Willem van Bree , Arthur Raymond Hubert van Zanten","doi":"10.1016/j.jointm.2024.08.003","DOIUrl":"10.1016/j.jointm.2024.08.003","url":null,"abstract":"<div><h3>Background</h3><div>Hypocalcemia is common among patients admitted to the intensive care unit (ICU). The administration of calcium in critically ill patients with hypocalcemia remains debated, as previous data on outcomes are conflicting, and subgroup analyses are lacking. This study aimed to investigate the association between parenteral calcium administration and clinical outcomes in critically ill patients who had hypocalcemia with and without sepsis.</div></div><div><h3>Methods</h3><div>This retrospective cohort study included individuals who developed hypocalcemia during the first 7 days of admission to a mixed medical-surgical adult ICU at a University-affiliated teaching hospital. Patients who were not receiving renal replacement therapy, and were admitted to the ICU for at least 48 h between October 1, 2015 and September 24, 2020, were included. The primary outcomes included all-cause 180-day mortality and time-to-shock resolution. Subgroup analyses were conducted in sepsis and nonsepsis patients with mild or moderate hypocalcemia, based on median splits. Proportional hazard regression analyses were performed to identify the association between parenteral calcium administration and outcome parameters.</div></div><div><h3>Results</h3><div>Among the 1100 patients who met the inclusion criteria, 427 (38.8 %) patients were admitted for sepsis and 576 (52.4 %) patients received parenteral calcium. Patients who received and did not receive parenteral calcium demonstrated no significant difference in 180-day mortality (adjusted hazard ratio [aHR] = 1.18, 95 % confidence interval [CI]: 0.90 to 1.56). Intravenous calcium administration reduced the probability of a shorter time to shock resolution (adjusted odds ratio = 0.81, 95 % CI: 0.70 to 0.94). Subgroup analyses in patients with and without sepsis indicated no significant association between calcium administration (aHR = 1.63, 95 % CI: 0.99 to 2.69) and 180-day mortality (aHR = 1.06, 95 % CI: 0.74 to 1.51). Notably, parenteral calcium was associated with an elevated risk of 90- and 180-day mortality in patients who had sepsis and mild hypocalcemia (aHR = 1.88, 95 % CI: 1.02 to 3.47 and aHR = 1.79, 95 % CI: 1.07 to 3.00, respectively).</div></div><div><h3>Conclusions</h3><div>Intravenous calcium administration did not provide survival or shock resolution benefits in ICU patients with hypocalcemia, and may even be harmful. Further research, including randomized controlled trials, are needed to confirm these findings.</div></div>","PeriodicalId":73799,"journal":{"name":"Journal of intensive medicine","volume":"5 2","pages":"Pages 151-159"},"PeriodicalIF":0.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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