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Wang TW, Zhou LL, Yuan J, Zhou WX, Wang HR, Yu TT, Zhai JC, Tang CB, Jiang W, Yu JQ, Zheng RQ, Yu HL, Shao J. Study of the relationship between iron metabolism disorders and sepsis-associated liver injury: A prospective observational study. World J Gastroenterol 2025; 31:104584. [PMID: 40248384 PMCID: PMC12001195 DOI: 10.3748/wjg.v31.i14.104584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2024] [Revised: 02/17/2025] [Accepted: 03/25/2025] [Indexed: 04/11/2025] Open
Abstract
BACKGROUND Sepsis-associated liver injury (SALI) refers to secondary liver function impairment caused by sepsis, patients with SALI often have worse clinical outcomes. The early identification and assessment of the occurrence and progression of SALI are pressing issues that urgently need to be resolved. AIM To investigate the relationship between iron metabolism and SALI. METHODS In this prospective study, 139 patients were recruited, with 53 assigned to the SALI group. The relationships between SALI and various iron metabolism-related biomarkers were examined. These biomarkers included serum iron (SI), total iron-binding capacity (TIBC), serum ferritin, transferrin, and transferrin saturation. To identify independent risk factors for SALI, both univariate and multivariate logistic regression analyses were performed. Additionally, receiver operating characteristic curve analysis was utilized to assess the predictive value of these biomarkers for the occurrence of SALI. RESULTS There were no statistically significant differences in age, sex, body mass index, Sequential Organ Failure Assessment scores (excluding liver function), or APACHE II scores between the two groups of patients. Compared with the sepsis group, the SALI group presented significantly higher SI (P < 0.001), TIBC (P < 0.001), serum ferritin (P = 0.001), transferrin (P = 0.005), and transferrin saturation levels (P < 0.001). Multivariate logistic regression analysis revealed that SI (odds ratio = 1.24, 95% confidence interval: 1.11-1.40, P < 0.001) and TIBC levels (odds ratio = 1.13, 95% confidence interval: 1.05-1.21, P < 0.001) were independent predictors of SALI. Receiver operating characteristic curve analysis revealed that SI and TIBC had areas under the curve of 0.816 and 0.757, respectively, indicating moderate predictive accuracy for SALI. CONCLUSION Iron metabolism disorders are closely associated with the development of SALI, and SI and TIBC may serve as potential predictive biomarkers. The combined use of SI and TIBC has superior diagnostic efficacy for SALI. These findings provide valuable insights for the early identification and management of SALI among patients with sepsis.
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Affiliation(s)
- Tian-Wei Wang
- Department of Intensive Care Unit, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou 225001, Jiangsu Province, China
| | - Lu-Lu Zhou
- Department of Intensive Care Unit, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou 225001, Jiangsu Province, China
| | - Jing Yuan
- Department of Functional Examination, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou 225001, Jiangsu Province, China
| | - Wen-Xin Zhou
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, Jiangsu Province, China
| | - Hao-Ran Wang
- Department of Intensive Care Unit, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou 225001, Jiangsu Province, China
| | - Ting-Ting Yu
- Department of Intensive Care Unit, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou 225001, Jiangsu Province, China
| | - Ji-Chao Zhai
- Department of Intensive Care Unit, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou 225001, Jiangsu Province, China
| | - Cheng-Bin Tang
- Department of Center for Cardiac Macrovascular Disease, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou 225001, Jiangsu Province, China
| | - Wei Jiang
- Department of Intensive Care Unit, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou 225001, Jiangsu Province, China
| | - Jiang-Quan Yu
- Department of Intensive Care Unit, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou 225001, Jiangsu Province, China
| | - Rui-Qiang Zheng
- Department of Intensive Care Unit, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou 225001, Jiangsu Province, China
| | - Hai-Long Yu
- Department of Neuro Intensive Care Unit, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou 225001, Jiangsu Province, China
- Department of Neurology, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou 225001, Jiangsu Province, China
| | - Jun Shao
- Department of Center for Cardiac Macrovascular Disease, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou 225001, Jiangsu Province, China
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Lee GR, Kim HS, Chung YJ, Kim EY. Venous-to-arterial carbon-dioxide tension difference as a useful predictor of patient prognosis after major surgery. Asian J Surg 2024; 47:2152-2160. [PMID: 38238140 DOI: 10.1016/j.asjsur.2024.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 12/13/2023] [Accepted: 01/05/2024] [Indexed: 05/05/2024] Open
Abstract
PURPOSE Change in venous-to-arterial carbon dioxide partial pressure difference[P(v-a)CO2] could be a useful marker to assess tissue perfusion status. Herein, we assessed the predictive values of postoperative P(v-a)CO2 measurements for mortality in critically ill patients after major surgery. The correlation between P(v-a)CO2 values and other conventional parameters of patient prognosis was also evaluated. METHODS Patients admitted to the intensive care unit(ICU) after abdominal surgery were enrolled. Arterial and venous blood gas analyses were performed within 1 h(T0) and after 24 h(T1) of admission to the ICU, respectively. The relationship between P(v-a)CO2 levels at T1 and other conventional parameters were assessed using a Bland-Altman plot. Logistic regression analysis was performed to examine the predisposing factors of mortality after surgery. RESULTS A total of 231 patients were finally analyzed. We divided the participants into the high PvaCO2 group[P(v-a)CO2 ≥ 8.6] and the low PvaCO2 group[P(v-a)CO2 < 8.6]. Seven-day-, 28-day, and in-hospital mortality were significantly higher in the high PvaCO2 group than in the low PvaCO2 group. There was significant agreement between P(v-a)CO2 values at T1 and APACHE II scores, lactate levels at T1 and total SOFA scores at T1. In multivariate logistic analysis, an increased P(v-a)CO2 value at T1 was the only significant risk factor of 7-day mortality after surgery. [odds ratio:1.341, 95%confidence interval: 1.050-1.714, p=0.019]. CONCLUSION P(v-a)CO2 measurements could be not only a significant predictor of postoperative prognosis, but also a useful surveillance parameter to maintain tissue perfusion after abdominal surgery in patients with a potential risk of fatal complication-related tissue hypoperfusion.
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Affiliation(s)
- Gyeo Ra Lee
- Division of Trauma and Surgical Critical Care, Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Hye Sung Kim
- Division of Trauma and Surgical Critical Care, Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Yoon Ji Chung
- Division of Trauma and Surgical Critical Care, Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Eun Young Kim
- Division of Trauma and Surgical Critical Care, Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
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Clarkin-Breslin RC, Brainard BM. Point-of-care and traditional erythrocyte sedimentation rate, point-of-care rheometry, and cell-free DNA concentration in dogs with or without systemic inflammation. J Vet Diagn Invest 2024; 36:177-186. [PMID: 38372154 PMCID: PMC10929639 DOI: 10.1177/10406387241226971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/20/2024] Open
Abstract
RBC aggregation and deformability characteristics are altered by inflammatory, microcirculatory, and hemorheologic disease. These changes can be indirectly evaluated using the erythrocyte sedimentation rate (ESR). Newer point-of-care devices employ syllectometry to evaluate RBC rheology, which can give information beyond the ESR. We evaluated 2 point-of-care rheometers (iSED and MIZAR; Alcor Scientific) in 52 dogs presented to a university teaching hospital. Whole blood samples were analyzed for correlation between the ESR using the Westergren (ESRw) method (measured at 1 h and 24 h) and the predicted ESR using iSED. Plasma fibrinogen and cell-free DNA concentrations were also measured as probable markers of inflammation. The iSED-predicted ESR was positively correlated to the ESRw method at 1 h (r = 0.74; p < 0.001) and 24 h (r = 0.62; p < 0.001). Comparing dogs with or without inflammation (defined as plasma fibrinogen concentration >3.5 g/L [350 mg/dL]), significant differences were seen in the MIZAR parameters of base point, amplitude, integral, and half-time. Median cell-free DNA concentrations were higher in the group of dogs with inflammation (117 [range: 51-266] ng/mL vs. 82.7 [range: 19-206] ng/mL; p = 0.024). The iSED-predicted ESR is a good predictor of the ESRw and was obtained more rapidly. Rheometric parameters measured by MIZAR may be useful in detecting inflammation and monitoring secondary morphologic and functional changes in canine RBCs.
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Affiliation(s)
- Rachel C. Clarkin-Breslin
- Department of Small Animal Medicine and Surgery, University of Georgia Veterinary Teaching Hospital, Athens, GA, USA
| | - Benjamin M. Brainard
- Department of Small Animal Medicine and Surgery, University of Georgia Veterinary Teaching Hospital, Athens, GA, USA
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Kommareddy A, Vagha JD, Meshram RJ. Navigating the Landscape of Hydrocortisone Administration in Septic Shock: Current Concepts and Future Directions. Cureus 2023; 15:e49870. [PMID: 38169849 PMCID: PMC10758589 DOI: 10.7759/cureus.49870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Accepted: 12/02/2023] [Indexed: 01/05/2024] Open
Abstract
Sepsis remains a formidable challenge in critical care medicine, often culminating in a life-threatening condition known as septic shock. This review article navigates the intricate landscape of hydrocortisone administration in septic shock management, delving into historical perspectives, current evidence, controversies, mechanisms of action, practical considerations, and the importance of precision medicine. Hydrocortisone's role as an adjunctive therapy is explored, highlighting its potential to stabilize hemodynamics, mitigate the inflammatory response, and improve patient outcomes. However, debates persist regarding patient selection, dosing regimens, safety profiles, and long-term consequences. The future of septic shock management lies in emerging therapies, precision medicine approaches, biomarker discovery, and targeted interventions. Moving forward, exploring novel therapeutic avenues, understanding patient-specific responses, and uncovering potential biomarkers will be crucial in advancing septic shock treatment strategies. Clinical guidelines provide a foundation, but individualized patient care, interdisciplinary collaboration, and ongoing research are essential to optimize treatment strategies. This article underscores the call for continued research and evidence-based practice as we strive to enhance the care of septic shock patients and pursue improved outcomes in this critical condition. Embracing future developments in the field will enable us to adapt and refine our approach, ultimately contributing to the advancement of septic shock management.
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Affiliation(s)
- Anirudh Kommareddy
- Pediatrics, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Jayant D Vagha
- Pediatrics, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Revat J Meshram
- Pediatrics, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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Zhang F, Mei X, Zhou P, Tian YP, Liu JX, Dong X, Yuan DS, Lin ZF, Zhang L, Lin JH, Li AJ, Deng X, Chen MZ, Yuan SY, Zha JJ, Shi B, Lin ZH, Guo SB. Anisodamine hydrobromide in the treatment of critically ill patients with septic shock: a multicenter randomized controlled trial. Ann Med 2023; 55:2264318. [PMID: 37791613 PMCID: PMC10552604 DOI: 10.1080/07853890.2023.2264318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 09/16/2023] [Indexed: 10/05/2023] Open
Abstract
BACKGROUND Septic shock is the development of sepsis to refractory circulatory collapse and metabolic derangements, characterized by persistent hypotension and increased lactate levels. Anisodamine hydrobromide (Ani HBr) is a Chinese medicine used to improve blood flow in circulatory disorders. The purpose of this study was to determine the therapeutic efficacy of Ani HBr in the treatment of patients with septic shock. METHODS This was a prospective, multicenter, randomized controlled trial focusing on patients with septic shock in 16 hospitals in China. Patients were randomly assigned in a 1:1 ratio to either the treatment group or the control group. The primary endpoint was 28-day mortality. The secondary outcomes included 7-day mortality, hospital mortality, hospital length of stay, vasopressor-free days within 7 days, etc. These indicators were measured and collected at 0, 6h, 24h, 48h, 72h and 7d after the diagnosis. RESULTS Between September 2017 and March 2021, 404 subjects were enrolled. 203 subjects received Ani HBr and 201 subjects were assigned to the control group. The treated group showed lower 28-day mortality than the control group. Stratified analysis further showed significant differences in 28-day mortality between the two groups for patients with a high level of illness severity. We also observed significant differences in 7-day mortality, hospital mortality and some other clinical indicators between the two groups. CONCLUSION Ani HBr might be an important adjuvant to conventional treatment to reduce 28-day mortality in patients with septic shock. A large-scale prospective randomized multicenter trial is warranted to confirm our results.
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Affiliation(s)
- Fang Zhang
- Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Xue Mei
- Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Ping Zhou
- Sichuan Provincial People’s Hospital, Chengdu, China
| | - Ying-Ping Tian
- Second Hospital of Hebei Medical University, Shijiazhuang, China
| | | | - Xu Dong
- Hebei Provincial Hospital of Chinese Medicine, Shijiazhuang, China
| | - Ding-Shan Yuan
- Affiliated Hospital of Nantong University, Nantong, China
| | | | - Lei Zhang
- Tongji Hospital of Tongji University, Wuhan, China
| | - Jin-Hao Lin
- Longyan People’s Hospital of Fujian, Longyan, China
| | - Ai-Jun Li
- Handan Central Hospital, Handan, China
| | - Xing Deng
- Second Hospital of Longyan, Longyan, China
| | | | | | | | - Bin Shi
- Yangpu Hospital of Tongji University, Shanghai, China
| | - Zhi-Hong Lin
- First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Shu-Bin Guo
- Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
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Özkul B, Sever İH, Yiğittürk G, Elgörmüş ÇS, Gür SG, Erbaş O. Demonstration of ameliorating effect of papaverine in sepsis-induced acute lung injury on rat model through radiology and histology. ULUS TRAVMA ACIL CER 2023; 29:963-971. [PMID: 37681716 PMCID: PMC10560817 DOI: 10.14744/tjtes.2023.73580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Revised: 07/26/2022] [Accepted: 07/25/2023] [Indexed: 09/09/2023]
Abstract
BACKGROUND Our target was to show the role of high mobility group box-1/receptor for (HMGB1/RAGE) interaction in feces intraperitoneal injection procedure (FIP)-induced acute lung injury (ALI) pathophysiology, to investigate the effect of papaverine on RAGE associated NF-κB pathway by determining the level of soluble RAGE (sRAGE) and HMGB1, and to support this hypothesis by evaluating inflammatory biochemical, oxidative stress markers, Hounsfield unit (HU) value in computed tomography (CT), and histo-pathological results. METHODS FIP was performed on 37 Wistar rats for creating a sepsis-induced ALI model. The animals were assigned into four groups as follows: Normal control (no treatment), placebo (FIP and saline), and receiving 20 mg/kg and 40 mg/kg per day papaverine. Twenty h after FIP, CT examination was performed for all animals, and HU value of the lung parenchyma was measured. The plasma levels of tumor necrosis factor (TNF)-α, HMGB1, sRAGE, C-reactive protein (CRP) and malondialdehyde (MDA), and lactic acid (LA) were determined and PaO2 and PaCO2 were measured from arterial blood sample. Lung damage was assessed by histopathological. RESULTS TNF-, IL-6, CRP, HMGB1, MDA, LA levels, histopathologic scores, and HU values of CT were significantly increased and sRAGE levels were decreased in the saline-treated group against normal group (all P<0.05). Papaverine significantly reversed all results regardless of the dose (all P<0.05) and demonstrated inhibition of HMGB1/RAGE interaction through increasing sRAGE levels and suppresses the pro-inflammatory cytokines. CONCLUSION We concluded that papaverine has ameliorating effects in rat model of ALI.
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Affiliation(s)
- Bahattin Özkul
- Department of Radiology, İstanbul Atlas University, İstanbul-Türkiye
| | | | - Gürkan Yiğittürk
- Department of Histology and Embryology, Muğla Sıtkı Koçman University, Muğla-Türkiye
| | | | | | - Oytun Erbaş
- Department of Physiology, Demiroğlu Bilim University, İstanbul-Türkiye
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Jouffroy R, Gilbert B, Tourtier JP, Bloch-Laine E, Ecollan P, Boularan J, Bounes V, Vivien B, Gueye P. Prehospital pulse pressure and mortality of septic shock patients cared for by a mobile intensive care unit. BMC Emerg Med 2023; 23:97. [PMID: 37626302 PMCID: PMC10464421 DOI: 10.1186/s12873-023-00864-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Accepted: 08/03/2023] [Indexed: 08/27/2023] Open
Abstract
BACKGROUND Septic shock medical treatment relies on a bundle of care including antibiotic therapy and hemodynamic optimisation. Hemodynamic optimisation consists of fluid expansion and norepinephrine administration aiming to optimise cardiac output to reach a mean arterial pressure of 65mmHg. In the prehospital setting, direct cardiac output assessment is difficult because of the lack of invasive and non-invasive devices. This study aims to assess the relationship between 30-day mortality and (i) initial pulse pressure (iPP) as (ii) pulse pressure variation (dPP) during the prehospital stage among patients cared for SS by a prehospital mobile intensive care unit (MICU). METHODS From May 09th, 2016 to December 02nd, 2021, septic shock patients requiring MICU intervention were retrospectively analysed. iPP was calculated as the difference between systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the first contact between the patient and the MICU team prior to any treatment and, dPP as the difference between the final PP (the difference between SBP and DBP at the end of the prehospital stage) and iPP divided by prehospital duration. To consider cofounders, the propensity score method was used to assess the relationship between (i) iPP < 40mmHg, (ii) positive dPP and 30-day mortality. RESULTS Among the 530 patients analysed, pulmonary, digestive, and urinary infections were suspected among 43%, 25% and 17% patients, respectively. The 30-day overall mortality rate reached 31%. Cox regression analysis showed an association between 30-day mortality and (i) iPP < 40mmHg; aHR of 1.61 [1.03-2.51], and (ii) a positive dPP; aHR of 0.56 [0.36-0.88]. CONCLUSION The current study reports an association between 30-day mortality rate and iPP < 40mmHg and a positive dPP among septic shock patients cared for by a prehospital MICU. A negative dPP could be helpful to identify septic shock with higher risk of poor outcome despite prehospital hemodynamic optimization.
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Affiliation(s)
- Romain Jouffroy
- Intensive Care Unit, Ambroise Paré Hospital, Assistance Publique Hôpitaux Paris and Paris Saclay University, 9 avenue Charles De Gaulle, Boulogne-Billancourt, 92100, France.
- Intensive Care Unit, Anaesthesiology, SAMU, Necker Enfants Malades Hospital, Assistance Publique - Hôpitaux Paris, Paris, France.
- Centre de recherche en Epidémiologie et Santé des Populations - U1018 INSERM, Paris Saclay University, Villejuif, France.
- Institut de Recherche bioMédicale et d'Epidémiologie du Sport - EA7329, INSEP - Paris University, Paris, France.
- EA 7525 Université des Antilles, Fort de France, France.
| | - Basile Gilbert
- Department of Emergency Medicine, SAMU 31, University Hospital of Toulouse, Toulouse, France
| | | | - Emmanuel Bloch-Laine
- Emergency Department, Cochin Hospital, Paris, France
- Emergency Department, SMUR, Hôtel Dieu Hospital - Assistance Publique - Hôpitaux Paris, Paris, France
| | - Patrick Ecollan
- Intensive Care Unit, SMUR, Pitie Salpêtriere Hospital, 47 Boulevard de l'Hôpital, Paris - Assistance Publique - Hôpitaux Paris, Paris, 75013, France
| | - Josiane Boularan
- SAMU 31, Centre Hospitalier Intercommunal Castres-Mazamet, Castres, France
| | - Vincent Bounes
- Department of Emergency Medicine, SAMU 31, University Hospital of Toulouse, Toulouse, France
| | - Benoit Vivien
- Intensive Care Unit, Anaesthesiology, SAMU, Necker Enfants Malades Hospital, Assistance Publique - Hôpitaux Paris, Paris, France
| | - Papa Gueye
- EA 7525 Université des Antilles, Fort de France, France
- SAMU 972, Centre Hospitalier Universitaire de Martinique, Fort-de-France Martinique, France
- EA 7525 University of the Antilles, Martinique, France
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Chen Y, Gong H, Tang D, Yu L, Long S, Zheng B, Luo D, Cai A. Liver proteomic analysis reveals the key proteins involved in host immune response to sepsis. PeerJ 2023; 11:e15294. [PMID: 37255592 PMCID: PMC10226476 DOI: 10.7717/peerj.15294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 04/04/2023] [Indexed: 06/01/2023] Open
Abstract
Background Sepsis is a serious infection-induced response in the host, which can result in life-threatening organ dysfunction. It is of great importance to unravel the relationship between sepsis and host immune response and its mechanisms of action. Liver is one of the most vulnerable organs in sepsis, however, the specific pathogenesis of septic liver injury has not been well understood at the protein level. Methods A total of 12 healthy Sprague-Dawley (SD) male rats aged from 6 to 8 weeks were adaptively housed in individual cages in the specific pathogen free animal room. These lab rats were grouped into two groups: treatment (N = 9) and control (N = 3) groups; only three mice from the treatment group survived and were used for subsequent experiments. A TMT-based proteomic analysis for liver tissue was performed in the septic rat model. Results A total of 37,012 unique peptides were identified, and then 6,166 proteins were determined, among which 5,701 were quantifiable. Compared to the healthy control group, the septic rat group exhibited 162 upregulated and 103 downregulated differentially expressed proteins (DEPs). The upregulated and downregulated DEPs were the most significantly enriched into the complement and coagulation cascades and metabolic pathways. Protein-protein interaction (PPI) analysis further revealed that the upregulated and downregulated DEPs each clustered in a PPI network. Several highly connected upregulated and downregulated DEPs were also enriched into the complement and coagulation cascades pathways and metabolic pathways, respectively. The parallel reaction monitoring (PRM) results of the selected DEPs were consistent with the results of the TMT analysis, supporting the proteomic data. Conclusion Our findings highlight the roles of complement and coagulation cascades and metabolic pathways that may play vital roles in the host immune response. The DEPs may serve as clinically potential treatment targets for septic liver injury.
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Affiliation(s)
- Yingying Chen
- Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China
| | - Hui Gong
- Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China
| | - Donge Tang
- Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Shenzhen, China
| | - Lan Yu
- Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China
| | - Shoubin Long
- Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China
| | - Bao Zheng
- Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China
| | - Dixian Luo
- Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China
| | - Anji Cai
- Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China
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Hansen M, Gillespie J, Riddick T, Samatham R, Baker S, Filer S, Xin H, Sheridan D. Evaluation of electronic measurement of capillary refill for Sepsis screening at ED triage. Am J Emerg Med 2023; 70:61-65. [PMID: 37201452 DOI: 10.1016/j.ajem.2023.05.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 05/03/2023] [Accepted: 05/08/2023] [Indexed: 05/20/2023] Open
Abstract
OBJECTIVE To evaluate the association between capillary refill time (CRT) measured by a medical device and sepsis among patients presenting to the Emergency Department (ED). METHODS This prospective observational study enrolled adult and pediatric patients during ED triage when sepsis was considered a potential diagnosis by the triage nurse. Patients were enrolled at an academic medical center between December 2020 and June 2022. CRT was measured by a research assistant using an investigational medical device. The outcomes included sepsis and septic shock defined using sep-3 criteria, septic shock defined as IV antibiotics and a vasopressor requirement, ICU admission, and hospital mortality. Other measures included patient demographics and vital signs at ED triage. We evaluated univariate associations between CRT and sepsis outcomes. RESULTS We enrolled 563 patients in the study, 48 met Sep-3 criteria, 5 met Sep-3 shock criteria, and 11 met prior septic shock criteria (IV antibiotics and vasopressors to maintain mean arterial pressure of 65). Sixteen patients were admitted to the ICU. The mean age was 49.1 years, and 51% of the cohort was female. The device measured CRT was significantly associated with the diagnosis of sepsis by sep-3 criteria (OR 1.23, 95% CI 1.06-1-43), septic shock by sep-3 criteria (OR 1.57, 95% CI 1.02-2.40), and septic shock defined as receipt of IV antibiotics and a vasopressor requirement (OR 1.37, 95% CI 1.03-1.82). Patients with CRT >3.5 s measured by the DCR device had an odds ratio of 4.67 (95%CI 1.31-16.1) of septic shock (prior definition), and an odds ratio of 3.97 (95% CI 1.99-7.92) of ICU admission, supporting the potential for the 3.5-s cutoff of the DCR measurement. CONCLUSIONS CRT measured by a medical device at ED triage was associated with the diagnosis of sepsis. Objective CRT measurement using a medical device may be a relatively simple way to improve sepsis diagnosis during ED triage.
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Affiliation(s)
- Matthew Hansen
- Center for Policy and Research in Emergency Medicine, Oregon Health & Science University, Portland, OR, United States of America; School of Medicine, Oregon Health & Science University, Portland, OR, United States of America; Promedix Inc, Portland, OR.
| | - Jordan Gillespie
- School of Medicine, Oregon Health & Science University, Portland, OR, United States of America
| | - Tyne Riddick
- School of Medicine, Oregon Health & Science University, Portland, OR, United States of America
| | - Ravi Samatham
- Department of Dermatology, Oregon Health & Science University, Portland, OR, United States of America
| | | | | | - Haichang Xin
- Center for Policy and Research in Emergency Medicine, Oregon Health & Science University, Portland, OR, United States of America
| | - David Sheridan
- Center for Policy and Research in Emergency Medicine, Oregon Health & Science University, Portland, OR, United States of America; School of Medicine, Oregon Health & Science University, Portland, OR, United States of America; Promedix Inc, Portland, OR
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Lin CK, Tsai YH, Kao KC, Lin CM, Zhou SK, Ho MC, Huang SY, Fang YH, Chang CC, Lee WC, Lee YL, Chen MC, Hsieh MJ, Lin YC, Hung MS, Kuo WC, Lin BS. Serum vascular endothelial growth factor affects tissue fluid accumulation and is associated with deteriorating tissue perfusion and oxygenation in severe sepsis: a prospective observational study. Eur J Med Res 2023; 28:155. [PMID: 37085944 PMCID: PMC10120235 DOI: 10.1186/s40001-023-01119-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 04/11/2023] [Indexed: 04/23/2023] Open
Abstract
BACKGROUND Positive fluid balance and tissue fluid accumulation are associated with adverse outcomes in sepsis. Vascular endothelial growth factor (VEGF) increases in sepsis, promotes vascular permeability, and may affect tissue fluid accumulation and oxygenation. We used near-infrared spectroscopy (NIRS) to estimate tissue hemoglobin (Hb) oxygenation and water (H2O) levels to investigate their relationship with serum VEGF levels. MATERIAL AND METHODS New-onset severe sepsis patients admitted to the intensive care unit were enrolled. Relative tissue concentrations of oxy-Hb ([HbO2]), deoxy-Hb ([HbR]), total Hb ([HbT]), and H2O ([H2O]) were estimated by near-infrared spectroscopy (NIRS) for three consecutive days and serum VEGF levels were measured. Comparisons between oliguric and non-oliguric patients were conducted and the correlations between variables were analyzed. RESULTS Among 75 eligible patients, compared with non-oliguric patients, oliguric patients were administrated more intravascular fluids (median [IQR], 1926.00 [1348.50-3092.00] mL/day vs. 1069.00 [722.00-1486.75] mL/day, p < 0.001) and had more positive daily net intake and output (mean [SD], 1,235.06 [1303.14] mL/day vs. 313.17 [744.75] mL/day, p = 0.012), lower [HbO2] and [HbT] over the three-day measurement (analyzed by GEE p = 0.01 and 0.043, respectively) and significantly higher [H2O] on the third day than on the first two days (analyzed by GEE p = 0.034 and 0.018, respectively). Overall, serum VEGF levels were significantly negatively correlated with [HbO2] and [HbT] (rho = - 0.246 and - 0.266, p = 0.042 and 0.027, respectively) but positively correlated with [H2O] (rho = 0.449, p < 0.001). Subgroup analysis revealed a significant correlation between serum VEGF and [H2O] in oliguric patients (rho = 0.532, p = 0.003). Multiple regression analysis determined the independent effect of serum VEGF on [H2O] (standardized coefficient = 0.281, p = 0.038). CONCLUSIONS In severe sepsis, oliguria relates to higher positive fluid balance, lower tissue perfusion and oxygenation, and progressive tissue fluid accumulation. Elevated serum VEGF is associated with worsening tissue perfusion and oxygenation and independently affects tissue fluid accumulation.
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Affiliation(s)
- Chin-Kuo Lin
- Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, No. 6, West Sec. Chiapu Rd., Putzu City, Chiayi County, 61363, Taiwan
- Graduate Institute of Clinical Medicine Sciences, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan Dist., Taoyuan, 33302, Taiwan
| | - Ying-Huang Tsai
- Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, No. 5, Fuxing St., Guishan Dist., Linkou, Taoyuan City, 333, Taiwan
| | - Kuo-Chin Kao
- Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, No. 5, Fuxing St., Guishan Dist., Linkou, Taoyuan City, 333, Taiwan
- Department of Respiratory Therapy, Chang Gung University College of Medicine, Taoyuan, 33302, Taiwan
- Department of Respiratory Therapy, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, 33305, Taiwan
| | - Chieh-Mo Lin
- Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, No. 6, West Sec. Chiapu Rd., Putzu City, Chiayi County, 61363, Taiwan
- Chang Gung University of Science and Technology, No. 2, West Sec. Jiapu Rd., Puzi City, Chiayi County, 61363, Taiwan
| | - Shao-Kui Zhou
- Institute of Imaging and Biomedical Photonics, National Yang Ming Chiao Tung University, No. 301, Gaotie 3Rd Road, Guiren Dist., Tainan City, 71150, Taiwan
| | - Meng-Chin Ho
- Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, No. 6, West Sec. Chiapu Rd., Putzu City, Chiayi County, 61363, Taiwan
| | - Shu-Yi Huang
- Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, No. 6, West Sec. Chiapu Rd., Putzu City, Chiayi County, 61363, Taiwan
- Chang Gung University of Science and Technology, No. 2, West Sec. Jiapu Rd., Puzi City, Chiayi County, 61363, Taiwan
| | - Yu-Hung Fang
- Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, No. 6, West Sec. Chiapu Rd., Putzu City, Chiayi County, 61363, Taiwan
| | - Che-Chia Chang
- Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, No. 6, West Sec. Chiapu Rd., Putzu City, Chiayi County, 61363, Taiwan
| | - Wei-Chun Lee
- Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, No. 6, West Sec. Chiapu Rd., Putzu City, Chiayi County, 61363, Taiwan
| | - Yueh-Lin Lee
- Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, No. 6, West Sec. Chiapu Rd., Putzu City, Chiayi County, 61363, Taiwan
| | - Min-Chi Chen
- Department of Public Health, Biostatistics Consulting Center, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Road, Guishan Dist., Guishan, Taoyuan City, 33302, Taiwan
- Department of Hematology and Oncology, Chang Gung Memorial Hospital, No. 6, West Sec. Chiapu Rd, Putzu City, Chiayi County, 61363, Taiwan
| | - Meng-Jer Hsieh
- Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, No. 5, Fuxing St., Guishan Dist., Linkou, Taoyuan City, 333, Taiwan
| | - Yu-Ching Lin
- Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, No. 6, West Sec. Chiapu Rd., Putzu City, Chiayi County, 61363, Taiwan
- Department of Respiratory Care, Chang Gung Memorial Hospital, No. 6, West Sec. Chiapu Rd, Putzu City, Chiayi County, 61363, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Road, Guishan Dist., Taoyuan City, 33302, Taiwan
| | - Ming-Szu Hung
- Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, No. 6, West Sec. Chiapu Rd., Putzu City, Chiayi County, 61363, Taiwan
- Department of Respiratory Care, Chang Gung Memorial Hospital, No. 6, West Sec. Chiapu Rd, Putzu City, Chiayi County, 61363, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Road, Guishan Dist., Taoyuan City, 33302, Taiwan
| | - Wen-Chun Kuo
- Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, No. 6, West Sec. Chiapu Rd., Putzu City, Chiayi County, 61363, Taiwan
| | - Bor-Shyh Lin
- Institute of Imaging and Biomedical Photonics, National Yang Ming Chiao Tung University, No. 301, Gaotie 3Rd Road, Guiren Dist., Tainan City, 71150, Taiwan.
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11
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de Miranda AC, Stefani FDCD, Vesco BCD, Carraro Júnior H, Assreuy J, Morello LG, de Menezes IAC. Relationship between peripheral ischemic microvascular reserve, persistent hyperlactatemia, and its temporal dynamics in sepsis: a post hoc study. CRITICAL CARE SCIENCE 2023; 35:177-186. [PMID: 37712807 PMCID: PMC10406409 DOI: 10.5935/2965-2774.20230348-en] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 03/25/2023] [Indexed: 09/16/2023]
Abstract
OBJECTIVE To measure the prognostic value of peripheral ischemic microvascular reserve in the context of persistent sepsis-induced hyperlactatemia and measure its influence on the temporal dynamics of lactate and the strength of association between these variables. METHODS This post hoc analysis of the peripheral perfusion index/postocclusive reactive hyperemia trial, an observational cohort study that enrolled patients with sepsis who persisted with lactate levels ≥ 2mmol/L after fluid resuscitation (with or without shock). Peripheral ischemic microvascular reserve was evaluated using the association of the peripheral perfusion index and postocclusive reactive hyperemia techniques. The cutoff point of ∆ peripheral perfusion index peak values (%) defined the groups with low (≤ 62%) and high peripheral ischemic microvascular reserve (> 62%). RESULTS A total of 108 consecutive patients with persistent sepsis-induced hyperlactatemia were studied. The high peripheral ischemic microvascular reserve group showed higher 28-day mortality than the low peripheral ischemic microvascular reserve group (p < 0.01). The temporal dynamics of lactate within the first 48 hours showed a rapid decrease in lactate levels in the low peripheral ischemic microvascular reserve group (p < 0.01). However, this result was not reproduced in the linear mixed effects model. A weak correlation between peripheral ischemic microvascular reserve (%) and lactate level (mmol/L) was observed within the first 24 hours (r = 0.23; p < 0.05). CONCLUSION The prognostic value of high peripheral ischemic microvascular reserve was confirmed in the context of persistent sepsis-induced hyperlactatemia. Although there was a weak positive correlation between peripheral ischemic microvascular reserve value and lactate level within the first 24 hours of sepsis diagnosis, the low peripheral ischemic microvascular reserve group appeared to have a faster decrease in lactate over the 48 hours of follow-up.
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Affiliation(s)
- Ana Carolina de Miranda
- Department of Internal Medicine, Hospital de Clínicas,
Universidade Federal do Paraná - Curitiba (PR), Brazil
| | | | - Bruna Cassia Dal Vesco
- Intensive Care Unit, Hospital de Clínicas, Universidade
Federal do Paraná - Curitiba (PR), Brazil
| | - Hipólito Carraro Júnior
- Intensive Care Unit, Hospital de Clínicas, Universidade
Federal do Paraná - Curitiba (PR), Brazil
| | - Jamil Assreuy
- Department of Pharmacology, Universidade Federal de Santa Catarina
- Florianópolis (SC), Brazil
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12
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Lombardi S, Francia P, Deodati R, Calamai I, Luchini M, Spina R, Bocchi L. COVID-19 Detection Using Photoplethysmography and Neural Networks. SENSORS (BASEL, SWITZERLAND) 2023; 23:2561. [PMID: 36904763 PMCID: PMC10007577 DOI: 10.3390/s23052561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 02/23/2023] [Accepted: 02/23/2023] [Indexed: 06/18/2023]
Abstract
The early identification of microvascular changes in patients with Coronavirus Disease 2019 (COVID-19) may offer an important clinical opportunity. This study aimed to define a method, based on deep learning approaches, for the identification of COVID-19 patients from the analysis of the raw PPG signal, acquired with a pulse oximeter. To develop the method, we acquired the PPG signal of 93 COVID-19 patients and 90 healthy control subjects using a finger pulse oximeter. To select the good quality portions of the signal, we developed a template-matching method that excludes samples corrupted by noise or motion artefacts. These samples were subsequently used to develop a custom convolutional neural network model. The model accepts PPG signal segments as input and performs a binary classification between COVID-19 and control samples. The proposed model showed good performance in identifying COVID-19 patients, achieving 83.86% accuracy and 84.30% sensitivity (hold-out validation) on test data. The obtained results indicate that photoplethysmography may be a useful tool for microcirculation assessment and early recognition of SARS-CoV-2-induced microvascular changes. In addition, such a noninvasive and low-cost method is well suited for the development of a user-friendly system, potentially applicable even in resource-limited healthcare settings.
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Affiliation(s)
- Sara Lombardi
- Department of Information Engineering, University of Florence, 50139 Florence, Italy
| | - Piergiorgio Francia
- Department of Information Engineering, University of Florence, 50139 Florence, Italy
| | | | | | | | | | - Leonardo Bocchi
- Department of Information Engineering, University of Florence, 50139 Florence, Italy
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13
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Angurana S, Thapa S. Quantification of microcirculatory failure: Is it far from reality? JOURNAL OF PEDIATRIC CRITICAL CARE 2023. [DOI: 10.4103/jpcc.jpcc_94_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
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14
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Mohamed Atef Refaat M, Ali Elkafrawy L, Elkabarity RH, Hafez AF. Effect of dexmedetomidine vs midazolam on the microcirculation of septic patients who are mechanically ventilated. EGYPTIAN JOURNAL OF ANAESTHESIA 2022. [DOI: 10.1080/11101849.2022.2109826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022] Open
Affiliation(s)
- Mostafa Mohamed Atef Refaat
- Department of Anesthesiology, Intensive Care and Pain Management, Faculty of Medicine, Ain-Shams University, Cairo, Egypt
| | - Laila Ali Elkafrawy
- Department of Anesthesiology, Intensive Care and Pain Management, Faculty of Medicine, Ain-Shams University, Cairo, Egypt
| | - Reem Hamdy Elkabarity
- Department of Anesthesiology, Intensive Care and Pain Management, Faculty of Medicine, Ain-Shams University, Cairo, Egypt
| | - Amr Fouad Hafez
- Department of Anesthesiology, Intensive Care and Pain Management, Faculty of Medicine, Ain-Shams University, Cairo, Egypt
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15
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Schneider L, Chalmers D, O'Beirn S, Greenberg M, Cave G. Premorbid beta blockade in sepsis is associated with a lower risk of a lactate concentration above the lactate threshold, a retrospective cohort study. Sci Rep 2022; 12:20843. [PMID: 36460714 PMCID: PMC9718750 DOI: 10.1038/s41598-022-25253-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 11/28/2022] [Indexed: 12/04/2022] Open
Abstract
Sepsis and septic shock represent a significant worldwide mortality burden. A lactate greater than 4 mmol/L is associated with increased mortality in septic patients. This is the concentration at the "lactate threshold" where serum lactate concentrations rise markedly with increased workload in exercise. Hyperlactatemia in both sepsis and exercise is contributed to by adrenergic agonism which stimulates aerobic glycolysis, increasing lactate production and decreasing lactate clearance. Our hypothesis is that in patients with sepsis, treatment with beta blockers in the community will be associated with a lower probability of initial lactate ≥ 4 mmol/L. This was single centre retrospective cohort study. We used an in-house SQL Database for all admissions to ICU/HDU for the 2017-2020 calendar years. The dataset was filtered for an APACHE III Diagnosis of sepsis. T-tests were used for continuous data, Chi squared and Fisher's exact test were used as appropriate to compare proportions. Logistic regression was used to investigate covariate effects. Of the 160 patient records analysed, 49 were prescribed beta blockers. A greater proportion of patients not prescribed beta blockers in the community had a first lactate ≥ 4 mmol/L (p = 0.049). This was robust to regression analysis. There was no difference in the proportion of patients with lactate ≥ 2 mmol/L (p = 0.52). In our cohort patients previously prescribed beta blockers were less likely to have a lactate of ≥ 4 mmol/mL. This supports the proposed mechanism that treatment with beta blockers increases the lactate threshold in sepsis. Further study is warranted.
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Affiliation(s)
- Liam Schneider
- Hawkes Bay Hospital Intensive Care Unit, Hastings, New Zealand
| | - Debra Chalmers
- Hawkes Bay Hospital Intensive Care Unit, Hastings, New Zealand
| | - Sean O'Beirn
- Hawkes Bay Hospital Intensive Care Unit, Hastings, New Zealand
| | | | - Grant Cave
- Hawkes Bay Hospital Intensive Care Unit, Hastings, New Zealand.
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16
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Lombardi S, Partanen P, Francia P, Calamai I, Deodati R, Luchini M, Spina R, Bocchi L. Classifying sepsis from photoplethysmography. Health Inf Sci Syst 2022; 10:30. [PMID: 36330224 PMCID: PMC9622958 DOI: 10.1007/s13755-022-00199-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Accepted: 10/09/2022] [Indexed: 11/05/2022] Open
Abstract
Sepsis is a life-threatening organ dysfunction. It is caused by a dysregulated immune response to an infection and is one of the leading causes of death in the intensive care unit (ICU). Early detection and treatment of sepsis can increase the survival rate of patients. The use of devices such as the photoplethysmograph could allow the early evaluation in addition to continuous monitoring of septic patients. The aim of this study was to verify the possibility of detecting sepsis in patients from whom the photoplethysmographic signal was acquired via a pulse oximeter. In this work, we developed a deep learning-based model for sepsis identification. The model takes a single input, the photoplethysmographic signal acquired by pulse oximeter, and performs a binary classification between septic and nonseptic samples. To develop the method, we used MIMIC-III database, which contains data from ICU patients. Specifically, the selected dataset includes 85 septic subjects and 101 control subjects. The PPG signals acquired from these patients were segmented, processed and used as input for the developed model with the aim of identifying sepsis. The proposed method achieved an accuracy of 76.37% with a sensitivity of 70.95% and a specificity of 81.04% on the test set. As regards the ROC curve, the Area Under Curve reached a value of 0.842. The results of this study indicate how the plethysmographic signal can be used as a warning sign for the early detection of sepsis with the aim of reducing the time for diagnosis and therapeutic intervention. Furthermore, the proposed method is suitable for integration in continuous patient monitoring.
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Affiliation(s)
- Sara Lombardi
- Department of Information Engineering, University of Florence, Via S. Marta, 3, 50139 Florence, Italy
| | - Petri Partanen
- Faculty of Information Technology and Electrical Engineering, University of Oulu, Pentti Kaiteran katu 1, 90570 Oulu, Finland
| | - Piergiorgio Francia
- Department of Information Engineering, University of Florence, Via S. Marta, 3, 50139 Florence, Italy
| | - Italo Calamai
- S.O.C. Anestesia e Rianimazione, Ospedale S. Giuseppe, viale Giovanni Boccaccio, 16, 50053 Empoli, Italy
| | - Rossella Deodati
- S.O.C. Anestesia e Rianimazione, Ospedale S. Giuseppe, viale Giovanni Boccaccio, 16, 50053 Empoli, Italy
| | - Marco Luchini
- S.O.C. Anestesia e Rianimazione, Ospedale S. Giuseppe, viale Giovanni Boccaccio, 16, 50053 Empoli, Italy
| | - Rosario Spina
- S.O.C. Anestesia e Rianimazione, Ospedale S. Giuseppe, viale Giovanni Boccaccio, 16, 50053 Empoli, Italy
| | - Leonardo Bocchi
- Department of Information Engineering, University of Florence, Via S. Marta, 3, 50139 Florence, Italy
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Immunomodulation by Hemoadsorption—Changes in Hepatic Biotransformation Capacity in Sepsis and Septic Shock: A Prospective Study. Biomedicines 2022; 10:biomedicines10102340. [PMID: 36289602 PMCID: PMC9598581 DOI: 10.3390/biomedicines10102340] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Revised: 09/13/2022] [Accepted: 09/14/2022] [Indexed: 11/26/2022] Open
Abstract
Background: Sepsis is often associated with liver dysfunction, which is an indicator of poor outcomes. Specific diagnostic tools that detect hepatic dysfunction in its early stages are scarce. So far, the immune modulatory effects of hemoadsorption with CytoSorb® on liver function are unclear. Method: We assessed the hepatic function by using the dynamic LiMAx® test and biochemical parameters in 21 patients with sepsis or septic shock receiving CytoSorb® in a prospective, observational study. Points of measurement: T1: diagnosis of sepsis or septic shock; T2 and T3: 24 h and 48 h after the start of CytoSorb®; T4: 24 h after termination of CytoSorb®. Results: The hepatic biotransformation capacity measured by LiMAx® was severely impaired in up to 95 % of patients. Despite a rapid shock reversal under CytoSorb®, a significant improvement in LiMAx® values appeared from T3 to T4. This decline and recovery of liver function were not reflected by common parameters of hepatic metabolism that remained mostly within the normal range. Conclusions: Hepatic dysfunction can effectively and safely be diagnosed with LiMAx® in ventilated ICU patients under CytoSorb®. Various static liver parameters are of limited use since they do not adequately reflect hepatic dysfunction and impaired hepatic metabolism.
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18
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Praxenthaler J, Kirchner C, Schwier E, Altmann S, Wittmer A, Henzler D, Köhler T. Case report: Early detection of mesenteric ischemia by intravital microscopy in a patient with septic shock. Front Med (Lausanne) 2022; 9:985977. [PMID: 36091703 PMCID: PMC9458872 DOI: 10.3389/fmed.2022.985977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Accepted: 08/04/2022] [Indexed: 11/17/2022] Open
Abstract
Gut ischemia is a frequent but underdiagnosed complication, especially in critically ill intensive care patients, and represents a special diagnostic challenge that can only be solved in an interdisciplinary manner. We report a case of a 54-year-old woman with acute mesenteric ischemia (AMI) as a cause of septic shock diagnosed by intravital microscopy (IVM) 2 days before visible necrotic changes in a multimodality approach. We show that intravital microscopy can be a serious alternative for the early diagnosis of mesenteric ischemia in the hands of the skilled. We use this case to discuss the value and clinical perspective of IVM in the intensive care setting.
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Affiliation(s)
- Janina Praxenthaler
- Department of Anesthesiology, Surgical Intensive Care, Emergency and Pain Medicine, Klinikum Herford, Ruhr University Bochum, Herford, Germany
- Department of Anesthesiology, Intensive Care and Pain Medicine, Kliniken Südostbayern, Klinikum Traunstein, Traunstein, Germany
| | - Carmen Kirchner
- Department of General and Visceral Surgery, Thoracic Surgery and Proctology, Klinikum Herford, Ruhr University Bochum, Herford, Germany
| | - Elke Schwier
- Department of Anesthesiology, Surgical Intensive Care, Emergency and Pain Medicine, Klinikum Herford, Ruhr University Bochum, Herford, Germany
| | - Simon Altmann
- Department of Anesthesiology, Surgical Intensive Care, Emergency and Pain Medicine, Klinikum Herford, Ruhr University Bochum, Herford, Germany
- Department of Anesthesiology, Intensive Care and Pain Medicine, Knappschaftskrankenhaus Bochum, Ruhr University Bochum, Bochum, Germany
| | - Axel Wittmer
- Institute of Pathology, Klinikum Herford, Herford, Germany
| | - Dietrich Henzler
- Department of Anesthesiology, Surgical Intensive Care, Emergency and Pain Medicine, Klinikum Herford, Ruhr University Bochum, Herford, Germany
| | - Thomas Köhler
- Department of Anesthesiology, Surgical Intensive Care, Emergency and Pain Medicine, Klinikum Herford, Ruhr University Bochum, Herford, Germany
- Department of Anesthesiology and Intensive Care Medicine, AMEOS-Klinikum Halberstadt, Halberstadt, Germany
- *Correspondence: Thomas Köhler,
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Cai L, Arbab AS, Lee TJ, Sharma A, Thomas B, Igarashi K, Raju RP. BACH1-Hemoxygenase-1 axis regulates cellular energetics and survival following sepsis. Free Radic Biol Med 2022; 188:134-145. [PMID: 35691510 PMCID: PMC10507736 DOI: 10.1016/j.freeradbiomed.2022.06.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 05/26/2022] [Accepted: 06/05/2022] [Indexed: 12/24/2022]
Abstract
Sepsis is a complex disease due to dysregulated host response to infection. Oxidative stress and mitochondrial dysfunction leading to metabolic dysregulation are among the hallmarks of sepsis. The transcription factor NRF2 (Nuclear Factor E2-related factor2) is a master regulator of the oxidative stress response, and the NRF2 mediated antioxidant response is negatively regulated by BTB and CNC homology 1 (BACH1) protein. This study tested whether Bach1 deletion improves organ function and survival following polymicrobial sepsis induced by cecal ligation and puncture (CLP). We observed enhanced post-CLP survival in Bach1-/- mice with a concomitantly increased liver HO-1 expression, reduced liver injury and oxidative stress, and attenuated systemic and tissue inflammation. After sepsis induction, the liver mitochondrial function was better preserved in Bach1-/- mice. Furthermore, BACH1 deficiency improved liver and lung blood flow in septic mice, as measured by SPECT/CT. RNA-seq analysis identified 44 genes significantly altered in Bach1-/- mice after sepsis, including HMOX1 and several genes in lipid metabolism. Inhibiting HO-1 activity by Zinc Protoporphyrin-9 worsened organ function in Bach1-/- mice following sepsis. We demonstrate that mitochondrial bioenergetics, organ function, and survival following experimental sepsis were improved in Bach1-/- mice through the HO-1-dependent mechanism and conclude that BACH1 is a therapeutic target in sepsis.
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Affiliation(s)
- Lun Cai
- Department of Pharmacology and Toxicology, Augusta University, Augusta, GA, 30912, USA
| | - Ali S Arbab
- Georgia Cancer Center, Augusta University, Augusta, GA, 30912, USA
| | - Tae Jin Lee
- Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA
| | - Ashok Sharma
- Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA
| | - Bobby Thomas
- Department of Pediatrics, Darby Children's Research Institute, Medical University of South Carolina, Charleston, SC, 29425, USA; Department of Neuroscience and Drug Discovery, Darby Children's Research Institute, Medical University of South Carolina, Charleston, SC, 29425, USA
| | - Kazuhiko Igarashi
- Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan
| | - Raghavan Pillai Raju
- Department of Pharmacology and Toxicology, Augusta University, Augusta, GA, 30912, USA.
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Maciel AT, Vitorio D, Osawa EA. Urine biochemistry assessment in the sequential evaluation of renal function: Time to think outside the box. Front Med (Lausanne) 2022; 9:912877. [PMID: 35957852 PMCID: PMC9360530 DOI: 10.3389/fmed.2022.912877] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 07/05/2022] [Indexed: 12/12/2022] Open
Abstract
Urine biochemistry (UB) remains a controversial tool in acute kidney injury (AKI) monitoring, being considered to be of limited value both in terms of AKI diagnosis and prognosis. However, many criticisms can be made to the studies that have established the so called “pre-renal paradigm” (used for decades as the essential physiological basis for UB assessment in AKI) as well as to more recent studies suggesting that UB has no utility in daily clinical practice. The aim of this article is to describe our hypothesis on how to interpret simple and widely recognized urine biochemical parameters from a novel perspective, propose the rationale for their sequential assessment and demonstrate their usefulness in AKI monitoring, especially in the critical care setting.
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Affiliation(s)
- Alexandre T. Maciel
- Research Department, Imed Group, São Paulo, Brazil
- Adult Intensive Care Unit, São Camilo Hospital–Pompéia Unit, São Paulo, Brazil
- *Correspondence: Alexandre T. Maciel,
| | - Daniel Vitorio
- Research Department, Imed Group, São Paulo, Brazil
- Adult Intensive Care Unit, São Camilo Hospital–Pompéia Unit, São Paulo, Brazil
| | - Eduardo A. Osawa
- Research Department, Imed Group, São Paulo, Brazil
- Adult Intensive Care Unit, São Camilo Hospital–Pompéia Unit, São Paulo, Brazil
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Jouffroy R, Gueye P. Impact of posture on capillary refilling time: Intravascular fluid also affects results. Am J Emerg Med 2022; 57:187. [PMID: 34972586 DOI: 10.1016/j.ajem.2021.12.048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 12/21/2021] [Indexed: 11/25/2022] Open
Affiliation(s)
- Romain Jouffroy
- EA 7525 Université des Antilles, France; Intensive Care Unit, Ambroise Paré Hospital, Assistance Publique Hôpitaux Paris and Paris Saclay University, Boulogne Billancourt, France; Centre de recherche en Epidémiologie et Santé des Populations, U1018 INSERM, Paris Saclay University, France; Institut de Recherche bioMédicale et d'Epidémiologie du Sport, EA7329, INSEP, Paris University, France.
| | - Papa Gueye
- EA 7525 Université des Antilles, France; SAMU 972 University Hospital of Martinique, Fort-de-France Martinique, France
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22
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Sena CM, Gonçalves L, Seiça R. Methods to evaluate vascular function: a crucial approach towards predictive, preventive, and personalised medicine. EPMA J 2022; 13:209-235. [PMID: 35611340 PMCID: PMC9120812 DOI: 10.1007/s13167-022-00280-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 05/02/2022] [Indexed: 11/06/2022]
Abstract
Endothelium, the gatekeeper of our blood vessels, is highly heterogeneous and a crucial physical barrier with the ability to produce vasoactive and protective mediators under physiological conditions. It regulates vascular tone, haemostasis, vascular inflammation, remodelling, and angiogenesis. Several cardio-, reno-, and cerebrovascular diseases begin with the dysfunction of endothelial cells, and more recently, COVID-19 was also associated with endothelial disease highlighting the need to monitor its function towards prevention and reduction of vascular dysfunction. Endothelial cells are an important therapeutic target in predictive, preventive, and personalised (3P) medicine with upmost importance in vascular diseases. The development of novel non-invasive techniques to access endothelial dysfunction for use in combination with existing clinical imaging modalities provides a feasible opportunity to reduce the burden of vascular disease. This review summarises recent advances in the principles of endothelial function measurements. This article presents an overview of invasive and non-invasive techniques to determine vascular function and their major advantages and disadvantages. In addition, the article describes mechanisms underlying the regulation of vascular function and dysfunction and potential new biomarkers of endothelial damage. Recognising these biomarkers is fundamental towards a shift from reactive to 3P medicine in the vascular field. Identifying vascular dysfunction earlier with non-invasive or minimally invasive techniques adds value to predictive diagnostics and targeted prevention (primary, secondary, tertiary care). In addition, vascular dysfunction is a potential target for treatments tailored to the person.
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Affiliation(s)
- Cristina M. Sena
- Institute of Physiology, Faculty of Medicine, University of Coimbra, Subunit 1, Polo 3, Azinhaga de Santa Comba, Celas, 3000-354 Coimbra, Portugal
- Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Lino Gonçalves
- Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal
- Department of Cardiology, Coimbra’s Hospital and University Centre (CHUC), Coimbra, Portugal
| | - Raquel Seiça
- Institute of Physiology, Faculty of Medicine, University of Coimbra, Subunit 1, Polo 3, Azinhaga de Santa Comba, Celas, 3000-354 Coimbra, Portugal
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Jouffroy R, Gilbert B, Thomas L, Bloch-Laine E, Ecollan P, Boularan J, Bounes V, Vivien B, Gueye PN. Association between prehospital shock index variation and 28-day mortality among patients with septic shock. BMC Emerg Med 2022; 22:87. [PMID: 35590250 PMCID: PMC9118768 DOI: 10.1186/s12873-022-00645-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Accepted: 04/13/2022] [Indexed: 11/10/2022] Open
Abstract
PURPOSE Septic shock (SS) hyperdynamic phase is characterized by tachycardia and low-blood pressure reflecting the relative hypovolemia. Shock index (SI), the ratio between heart rate and systolic blood pressure, is a simple objective tool, usable for SS prognosis assessment. This study aims to evaluate the relationship between prehospital SI variation and 28-day mortality of SS patients initially cared for in prehospital setting by a mobile intensive care unit (mICU). METHODS From April 6th, 2016 to December 31st, 2020, 406 patients with SS requiring prehospital mICU were retrospectively analyzed. Initial SI, i.e. first measurement after mICU arrival to the scene, and final SI, i.e. last measurement of the prehospital stage, were used to calculate delta SI (initial SI-final SI) and to define positive and negative delta SI. A survival analysis after propensity score matching compared the 28-day mortality of SS patients with positive/negative delta SI. RESULTS The main suspected origins of infection were pulmonary (42%), digestive (25%) and urinary (17%). The 28-day overall mortality reached 29%. Cox regression analysis revealed a significant association between 28-day mortality and delta SI. A negative delta SI was associated with an increase in mortality (adjusted hazard ratio (HRa) of 1.88 [1.07-3.31] (p = 0.03)), whereas a positive delta SI was associated with a mortality decrease (HRa = 0.53 [0.30-0.94] (p < 10-3)). CONCLUSION Prehospital hemodynamic delta SI among SS patients cared for by a mICU is associated with 28-day mortality. A negative prehospital delta SI could help physicians to identify SS with higher risk of 28-day mortality.
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Affiliation(s)
- Romain Jouffroy
- Intensive Care Unit, Ambroise Paré Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.
- IRMES - Institute for Research in Medicine and Epidemiology of Sport, INSEP, Paris, France.
- INSERM U-1018, Centre de Recherche en Epidémiologie Et Santé Des Populations - U1018 INSERM, Paris Saclay University, Paris, France.
- Université de Paris, 7329, Paris, EA, France.
- Intensive Care Unit, Anaesthesiology, SAMU, Necker Enfants Malades Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.
| | - Basile Gilbert
- Department of Emergency Medicine, University Hospital of Toulouse, SAMU 31, Toulouse, France
| | - Léa Thomas
- Hôpital d'Instruction Des Armées Bégin, Paris, France
| | - Emmanuel Bloch-Laine
- Emergency Department, Cochin Hospital, Paris, France & Emergency Department, SMUR, Hôtel Dieu Hospital, Paris, France
| | - Patrick Ecollan
- Intensive Care Unit, SMUR, Pitie Salpêtriere Hospital, 47 Boulevard de l'Hôpital, 75013, Paris, France
| | | | - Vincent Bounes
- Department of Emergency Medicine, University Hospital of Toulouse, SAMU 31, Toulouse, France
| | - Benoit Vivien
- Intensive Care Unit, Anaesthesiology, SAMU, Necker Enfants Malades Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France
| | - Papa-Ngalgou Gueye
- SAMU 972 CHU de Martinique Pierre Zobda Quitman Hospital, Fort-de-France Martinique, France
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24
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Awuah A, Moore JS, Nesbit MA, Ruddock MW, Brennan PF, Mailey JA, McNeil AJ, Jing M, Finlay DD, Trucco E, Kurth MJ, Watt J, Lamont JV, Fitzgerald P, Spence MS, McLaughlin JAD, Moore TCB. A novel algorithm for cardiovascular screening using conjunctival microcirculatory parameters and blood biomarkers. Sci Rep 2022; 12:6545. [PMID: 35449196 PMCID: PMC9023476 DOI: 10.1038/s41598-022-10491-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Accepted: 03/15/2022] [Indexed: 11/30/2022] Open
Abstract
Microvascular haemodynamic alterations are associated with coronary artery disease (CAD). The conjunctival microcirculation can easily be assessed non-invasively. However, the microcirculation of the conjunctiva has not been previously explored in clinical algorithms aimed at identifying patients with CAD. This case–control study involved 66 patients with post-myocardial infarction and 66 gender-matched healthy controls. Haemodynamic properties of the conjunctival microcirculation were assessed with a validated iPhone and slit lamp-based imaging tool. Haemodynamic properties were extracted with semi-automated software and compared between groups. Biomarkers implicated in the development of CAD were assessed in combination with conjunctival microcirculatory parameters. The conjunctival blood vessel parameters and biomarkers were used to derive an algorithm to aid in the screening of patients for CAD. Conjunctival blood velocity measured in combination with the blood biomarkers (N-terminal pro-brain natriuretic peptide and adiponectin) had an area under receiver operator characteristic curve (AUROC) of 0.967, sensitivity 93.0%, specificity 91.5% for CAD. This study demonstrated that the novel algorithm which included a combination of conjunctival blood vessel haemodynamic properties, and blood-based biomarkers could be used as a potential screening tool for CAD and should be validated for potential utility in asymptomatic individuals.
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Affiliation(s)
- Agnes Awuah
- Biomedical Sciences Research Institute, Ulster University, Cromore Road, Coleraine, BT52 1SA, UK
| | - Julie S Moore
- Biomedical Sciences Research Institute, Ulster University, Cromore Road, Coleraine, BT52 1SA, UK
| | - M Andrew Nesbit
- Biomedical Sciences Research Institute, Ulster University, Cromore Road, Coleraine, BT52 1SA, UK
| | - Mark W Ruddock
- Clinical Studies Group, Randox Laboratories Ltd, 55 Diamond Road, Crumlin, BT29 4QY, UK
| | - Paul F Brennan
- Department of Cardiology, Royal Victoria Hospital, Belfast Health and Social Care Trust, 274 Grosvenor Road, Belfast, BT12 6BA, UK
| | - Jonathan A Mailey
- Department of Cardiology, Royal Victoria Hospital, Belfast Health and Social Care Trust, 274 Grosvenor Road, Belfast, BT12 6BA, UK
| | - Andrew J McNeil
- VAMPIRE Project, Computing (SSEN), University of Dundee, Dundee, DD1 4HN, UK
| | - Min Jing
- Nanotechnology and Integrated Bioengineering Centre (NIBEC), Ulster University, Jordanstown, BT37 0QB, UK
| | - Dewar D Finlay
- Nanotechnology and Integrated Bioengineering Centre (NIBEC), Ulster University, Jordanstown, BT37 0QB, UK
| | - Emanuele Trucco
- VAMPIRE Project, Computing (SSEN), University of Dundee, Dundee, DD1 4HN, UK
| | - Mary Jo Kurth
- Clinical Studies Group, Randox Laboratories Ltd, 55 Diamond Road, Crumlin, BT29 4QY, UK
| | - Joanne Watt
- Clinical Studies Group, Randox Laboratories Ltd, 55 Diamond Road, Crumlin, BT29 4QY, UK
| | - John V Lamont
- Clinical Studies Group, Randox Laboratories Ltd, 55 Diamond Road, Crumlin, BT29 4QY, UK
| | - Peter Fitzgerald
- Clinical Studies Group, Randox Laboratories Ltd, 55 Diamond Road, Crumlin, BT29 4QY, UK
| | - Mark S Spence
- Department of Cardiology, Royal Victoria Hospital, Belfast Health and Social Care Trust, 274 Grosvenor Road, Belfast, BT12 6BA, UK
| | - James A D McLaughlin
- Nanotechnology and Integrated Bioengineering Centre (NIBEC), Ulster University, Jordanstown, BT37 0QB, UK
| | - Tara C B Moore
- Biomedical Sciences Research Institute, Ulster University, Cromore Road, Coleraine, BT52 1SA, UK.
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Jouffroy R, Hajjar A, Gilbert B, Tourtier JP, Bloch-Laine E, Ecollan P, Boularan J, Bounes V, Vivien B, Gueye PN. Prehospital norepinephrine administration reduces 30-day mortality among septic shock patients. BMC Infect Dis 2022; 22:345. [PMID: 35387608 PMCID: PMC8988327 DOI: 10.1186/s12879-022-07337-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2021] [Accepted: 02/21/2022] [Indexed: 11/23/2022] Open
Abstract
Background Despite differences in time of sepsis recognition, recent studies support that early initiation of norepinephrine in patients with septic shock (SS) improves outcome without an increase in adverse effects. This study aims to investigate the relationship between 30-day mortality in patients with SS and prehospital norepinephrine infusion in order to reach a mean blood pressure (MAP) > 65 mmHg at the end of the prehospital stage. Methods From April 06th, 2016 to December 31th, 2020, patients with SS requiring prehospital Mobile Intensive Care Unit intervention (MICU) were retrospectively analysed. To consider cofounders, the propensity score method was used to assess the relationship between prehospital norepinephrine administration in order to reach a MAP > 65 mmHg at the end of the prehospital stage and 30-day mortality.
Results Four hundred and seventy-eight patients were retrospectively analysed, among which 309 patients (65%) were male. The mean age was 69 ± 15 years. Pulmonary, digestive, and urinary infections were suspected among 44%, 24% and 17% patients, respectively. One third of patients (n = 143) received prehospital norepinephrine administration with a median dose of 1.0 [0.5–2.0] mg h−1, among which 84 (69%) were alive and 38 (31%) were deceased on day 30 after hospital-admission. 30-day overall mortality was 30%. Cox regression analysis after the propensity score showed a significant association between prehospital norepinephrine administration and 30-day mortality, with an adjusted hazard ratio of 0.42 [0.25–0.70], p < 10–3. Multivariate logistic regression of IPTW retrieved a significant decrease of 30-day mortality among the prehospital norepinephrine group: ORa = 0.75 [0.70–0.79], p < 10–3.
Conclusion In this study, we report that prehospital norepinephrine infusion in order to reach a MAP > 65 mmHg at the end of the prehospital stage is associated with a decrease in 30-day mortality in patients with SS cared for by a MICU in the prehospital setting. Further prospective studies are needed to confirm that very early norepinephrine infusion decreases septic shock mortality.
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Affiliation(s)
- Romain Jouffroy
- Intensive Care Unit, Ambroise Paré Hospital, Assistance Publique Hôpitaux Paris and Paris Saclay University, 9 avenue Charles de Gaulle, 92100, Boulogne-Billancourt, France. .,Intensive Care Unit, Anaesthesiology, SAMU, Necker Enfants Malades Hospital, Assistance Publique, Hôpitaux Paris, Paris, France. .,Centre de Recherche en Epidémiologie et Santé des Populations, U1018 INSERM, Paris Saclay University, Paris, France. .,Institut de Recherche bioMédicale et d'Epidémiologie du Sport, EA7329, INSEP, Paris University, Paris, France. .,EA 7525 Université des Antilles, Pointe-à-Pitre, France.
| | - Adèle Hajjar
- Intensive Care Unit, Ambroise Paré Hospital, Assistance Publique Hôpitaux Paris and Paris Saclay University, 9 avenue Charles de Gaulle, 92100, Boulogne-Billancourt, France
| | - Basile Gilbert
- Department of Emergency Medicine, SAMU 31, University Hospital of Toulouse, Toulouse, France
| | | | - Emmanuel Bloch-Laine
- Emergency Department, Cochin Hospital, Paris, France.,Emergency Department, SMUR, Hôtel Dieu Hospital, Assistance Publique, Hôpitaux Paris, Paris, France
| | - Patrick Ecollan
- Intensive Care Unit, SMUR, Pitie Salpêtriere Hospital, Assistance Publique, Hôpitaux Paris, 47 Boulevard de l'Hôpital, 75013, Paris, France
| | - Josiane Boularan
- SAMU 31, Centre Hospitalier Intercommunal Castres-Mazamet, Castres, France
| | - Vincent Bounes
- Department of Emergency Medicine, SAMU 31, University Hospital of Toulouse, Toulouse, France
| | - Benoit Vivien
- Intensive Care Unit, Anaesthesiology, SAMU, Necker Enfants Malades Hospital, Assistance Publique, Hôpitaux Paris, Paris, France
| | - Papa-Ngalgou Gueye
- EA 7525 Université des Antilles, Pointe-à-Pitre, France.,SAMU 972 University Hospital of Martinique, Fort-de-France, Martinique, France
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Jahandideh F, Panahi S, Noble RMN, Gragasin FS, Khadaroo RG, Macala KF, Bourque SL. Characterization of Systemic and Regional Hemodynamics and Vascular Dysfunction in Mice with Fecal Induced Peritonitis. Biomedicines 2022; 10:biomedicines10020470. [PMID: 35203689 PMCID: PMC8962278 DOI: 10.3390/biomedicines10020470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 02/08/2022] [Accepted: 02/16/2022] [Indexed: 01/09/2023] Open
Abstract
Sepsis is associated with circulatory dysfunction contributing to disturbed blood flow and organ injury. Decreased organ perfusion in sepsis is attributed, in part, to the loss of vasoregulatory mechanisms. Identifying which vascular beds are most susceptible to dysfunction is important for monitoring the recovery of organ function and guiding interventions. This study aimed to investigate the development of vascular dysfunction as sepsis progressed to septic shock. Anesthetized C57Bl/6 mice were instrumented with a fiberoptic pressure sensor in the carotid artery for blood pressure measurements. In subgroups of mice, regional blood flow measurements were taken by positioning a perivascular flow probe around either the left carotid, left renal, or superior mesenteric arteries. Hemodynamic parameters and their responsiveness to bolus doses of vasoactive drugs were recorded prior to and continuously after injection of fecal slurry (1.3 mg/g body weight) for 4 h. Fecal slurry-induced peritonitis reduced mean arterial pressure (62.7 ± 2.4 mmHg vs. 37.5 ± 3.2 mmHg in vehicle and septic mice, respectively), impaired cardiac function, and eventually reduced organ blood flow (71.9%, 66.8%, and 65.1% in the superior mesenteric, renal, and carotid arteries, respectively). The mesenteric vasculature exhibited dysregulation before the renal and carotid arteries, and this underlying dysfunction preceded the blood pressure decline and impaired organ blood flow.
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Affiliation(s)
- Forough Jahandideh
- Department of Anesthesiology & Pain Medicine, University of Alberta, Edmonton, AB T6G 2G3, Canada; (F.J.); (S.P.); (F.S.G.); (K.F.M.)
- Women and Children’s Health Research Institute, University of Alberta, Edmonton, AB T6G 1C9, Canada;
| | - Sareh Panahi
- Department of Anesthesiology & Pain Medicine, University of Alberta, Edmonton, AB T6G 2G3, Canada; (F.J.); (S.P.); (F.S.G.); (K.F.M.)
| | - Ronan M. N. Noble
- Women and Children’s Health Research Institute, University of Alberta, Edmonton, AB T6G 1C9, Canada;
- Department of Pediatrics, University of Alberta, Edmonton, AB T6G 2G3, Canada
| | - Ferrante S. Gragasin
- Department of Anesthesiology & Pain Medicine, University of Alberta, Edmonton, AB T6G 2G3, Canada; (F.J.); (S.P.); (F.S.G.); (K.F.M.)
- Women and Children’s Health Research Institute, University of Alberta, Edmonton, AB T6G 1C9, Canada;
| | - Rachel G. Khadaroo
- Department of Critical Care Medicine, University of Alberta, Edmonton, AB T6G 2G3, Canada;
- Department of Surgery, University of Alberta, Edmonton, AB T6G 2G3, Canada
| | - Kimberly F. Macala
- Department of Anesthesiology & Pain Medicine, University of Alberta, Edmonton, AB T6G 2G3, Canada; (F.J.); (S.P.); (F.S.G.); (K.F.M.)
- Women and Children’s Health Research Institute, University of Alberta, Edmonton, AB T6G 1C9, Canada;
- Department of Critical Care Medicine, University of Alberta, Edmonton, AB T6G 2G3, Canada;
| | - Stephane L. Bourque
- Department of Anesthesiology & Pain Medicine, University of Alberta, Edmonton, AB T6G 2G3, Canada; (F.J.); (S.P.); (F.S.G.); (K.F.M.)
- Women and Children’s Health Research Institute, University of Alberta, Edmonton, AB T6G 1C9, Canada;
- Department of Pediatrics, University of Alberta, Edmonton, AB T6G 2G3, Canada
- Department of Pharmacology, University of Alberta, Edmonton, AB T6G 2G3, Canada
- Correspondence: ; Tel.: +1-780-492-6000
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Central Venous-to-Arterial CO2 Difference-Assisted Goal-Directed Hemodynamic Management During Major Surgery-A Randomized Controlled Trial. Anesth Analg 2022; 134:1010-1020. [PMID: 35027515 DOI: 10.1213/ane.0000000000005833] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND Different goals have guided goal-directed therapy (GDT). Protocols aiming for central venous-to-arterial carbon dioxide gap (DCO2) <6 mm Hg have improved organ function in septic shock. Evidence for use of DCO2 in the perioperative period is scarce. We aimed to determine if a GDT protocol using central venous saturation of oxygen (SCvo2) and DCO2 reduced organ dysfunction and intensive care unit (ICU) stay in American Society of Anesthesiologist (ASA) I and II patients undergoing major surgeries compared to pragmatic goal-directed care. METHODS One hundred patients were randomized. Arterial and venous blood-gas values were recorded every 2 hours perioperatively for all patients. Intervention group (GrI) with access to both values was managed per protocol based on DCO2 and SCvo2. Dobutamine infusion 3 to 5 µg/kg/min started if DCO2 >6 mm Hg after correcting all macrocirculatory end points. Control group (GrC) had access only to arterial-gas values and managed per "conventional" goals without DCO2 or SCvo2. Patients were followed for 48 hours after surgery. Organ dysfunction, sequential organ failure assessment (SOFA) scores-primary outcome, length of stay in ICU, and duration of postoperative mechanical ventilation and hospital stay were recorded. The patient, surgeons, ICU team, and analyzer were blinded to group allocation. RESULTS The groups (44 each) did not significantly differ with respect to baseline characteristics. Perioperative fluids, blood products, and vasopressors used did not significantly differ. The GrI had less organ dysfunction although not significant (79% vs 66%; P = .2). Length of ICU stay in the GrI was significantly less (1.52; standard deviation [SD], 0.82 vs 2.18; SD, 1.08 days; P = .002). Mechanical ventilation duration (0.9 days in intervention versus 0.6 days in control; P = .06) and length of hospital stay did not significantly differ between the groups. Perioperative DCO2 (5.8 vs 8.4 mm Hg; P < .001) and SCvo2 (73.5 vs 68.4 mm Hg; P < .001) were significantly better in the GrI. CONCLUSIONS GDT guided by DCO2 did not improve organ function in our cohort. It resulted in greater use of dobutamine, improved tissue oxygen parameters, and decreased length of ICU stay. More evidence is needed for the routine use of DCO2 in sicker patients. In the absence of cardiac output monitors, it may be a readily available, less-expensive, and underutilized parameter for major surgical procedures.
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Elevated Venous to Arterial Carbon Dioxide Gap and Anion Gap Are Associated with Poor Outcome in Cardiogenic Shock Requiring Extracorporeal Membrane Oxygenation Support. ASAIO J 2021; 67:263-269. [PMID: 33627599 DOI: 10.1097/mat.0000000000001215] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Optimal management of cardiogenic shock requiring extracorporeal membrane oxygenation (ECMO) is still an evolving area in which assessment and optimization of the microcirculation may be critically important. We hypothesized that the venous arterial carbon dioxide gap (P(v-a)CO2 gap); the ratio of this gap to arterio-venous oxygen content (P(v-a)CO2/C(a-v)O2 ratio) and the anion gap would be early indicators of microcirculatory status and useful parameters for outcome prediction during ECMO support. We retrospectively reviewed 31 cardiogenic shock patients requiring veno-arterial ECMO, calculating P(v-a)CO2 gap and P(v-a)CO2/C(a-v)O2 ratios in the first 36 hours and the final 24 hours of ECMO support. Sixteen patients (52%) survived and 15 (48%) died. After 24 hours of ECMO support, the P(v-a)CO2 gap (4.9 ± 1.5 vs. 6.8 ± 1.9 mm Hg; p = 0.004) and anion gap (5.2 ± 1.8 vs. 8.7 ± 2.7 mmol/L; p < 0.001) were significantly higher in non-survivors. In the final 24 hours of ECMO support, the P(v-a)CO2 gap (3.5 ± 1.6 vs. 10.5 ± 3.2 mm Hg; p < 0.001), P(v-a)CO2/C(a-v)O2 ratio (1.1 ± 0.5 vs. 2.7 ± 1.0; p < 0.001), anion gap (5.1 ± 3.0 vs. 9.3 ± 5.9 mmol/L; p = 0.02), and lactate (median 1.0 [interquartile range {IQR}: 0.7-1.5] vs. 2.8 [IQR: 1.7-7.7] mmol/L; p = <0.001) were all significantly lower in survivors. Increasing P(v-a)CO2 gap and increasing anion gap were significantly associated with increased risk of mortality. Optimum cut-points for prediction of mortality were 6 mm Hg for P(v-a)CO2 gap in combination with an anion gap above 6 mmol/L in the first 24 hours of ECMO in patients with cardiogenic shock requiring ECMO.
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Intraperitoneal contamination index (Hajibandeh index) predicts nature of peritoneal contamination and risk of postoperative mortality in patients with acute abdominal pathology: a prospective multicentre cohort study. Int J Colorectal Dis 2021; 36:1023-1031. [PMID: 33409563 DOI: 10.1007/s00384-020-03822-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/15/2020] [Indexed: 02/04/2023]
Abstract
OBJECTIVES To assess whether intraperitoneal contamination index (ICI) (Hajibandeh index) derived from combined levels of CRP, lactate, neutrophils, lymphocytes, and albumin can predict the nature of intraperitoneal contamination in patients with acute abdominal pathology and to assess whether ICI can predict postoperative mortality in patients undergoing emergency laparotomy. METHODS In order to prospectively validate the ICI, developed and validated retrospectively in our previous study, a multicentre prospective cohort study was conducted between January 2019 and June 2020 including all adult patients who presented with acute abdominal pathology requiring emergency laparotomy. ROC curve analysis was performed to determine discrimination and cut-off values of preoperative ICI that could predict the nature of intraperitoneal contamination and postoperative mortality. RESULTS Overall, 269 patients were included in the prospective validation cohort which were compared with 234 patients in the primary cohort and 234 patients in the retrospective validation cohort. The analyses identified ICI of 24.76 as cut-off value for purulent contamination (AUC: 0.78, P < 0.0001; sensitivity: 82.4%, specificity: 60.9%); ICI of 33.84 as cut-off value for feculent contamination (AUC: 0.78, P < 0.0001; sensitivity: 82%, specificity: 67.8%), and ICI of 33.47 as cut-off value for postoperative mortality (AUC: 0.70, P < 0.0001; sensitivity: 72.7%, specificity: 58.47%). The results of the prospective validation cohort were comparable with the results of the primary and retrospective validation cohorts. CONCLUSIONS Hajibandeh index predicts the presence of purulent and feculent intraperitoneal contamination in patients with acute abdominal pathology and postoperative mortality in patients undergoing emergency laparotomy. Future studies should investigate the effect of ICI use on the accuracy of preoperative prognostic scoring tools and on patient selection for operative or non-operative management of underlying abdominal pathology.
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Xantus G, Allen P, Kanizsai P. Blind spot in sepsis management - Tissue level changes in microcirculation. Physiol Int 2021. [PMID: 33844643 DOI: 10.1556/2060.2021.00011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Accepted: 01/20/2021] [Indexed: 11/19/2022]
Abstract
In sepsis cytokine-mediated inflammation, clotting cascade activation and glycocalyx shedding impair both function and structure of the microcirculation, compromising adequate tissue oxygenation/perfusion. Such mismatch results in "dysoxia", an imbalance in mitochondrial respiration.Microvessel injuries can be grouped into four types: cytotoxic oedema, micro-vessel heterogeneity, sluggish/absent flow, and focal anaemia. Recognition of such diversity in microcirculatory pathology, alongside with the implementation of novel biomarkers might reveal previously unobserved heterogeneity in adults diagnosed with sepsis. Early identification of distinct subtypes may help not only to better stratify disease severity but may also provide explanation to the often seen insufficient/absent response to resuscitative treatment. Experimental evidence suggests that impaired microcirculatory flow may correlate with organ dysfunction and mortality. Therefore, reliable/reproducible diagnostic tools, that provide real-time information about the dynamic state of the microcirculation, might be practice changers in managing the critically ill.The sublingual mucosa and the nailfolds provide easy access to microcirculation via hand-held, point-of-care devices. Accessing these windows, clinicians may recognise, understand and potentially correct the underlying tissue oxygenation/perfusion mismatch. This new clinical information might facilitate an individualised approach vs protocolised care aiming to administer the right balance of intravenous fluids/vasopressors, time/dose auxiliary treatment modalities and, most importantly, might also guide determining the optimal duration of resuscitation to avoid/minimise harm and maximise benefits in sepsis management. However, before every-day clinical use of such point-of-care microcameras, validation studies are needed to establish not only feasibility but reliability and reproducibility as well.
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Affiliation(s)
- G Xantus
- 1School of Medicine, Cardiff University, Cardiff CF10 3AT, UK
| | - P Allen
- 2Rural Clinical School, College of Health and Medicine, Burnie, Tasmania, 7320, Australia
| | - P Kanizsai
- 3Department of Emergency Medicine, Clinical Centre, University of Pécs, Pécs, Hungary
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Dietrich M, Marx S, von der Forst M, Bruckner T, Schmitt FCF, Fiedler MO, Nickel F, Studier-Fischer A, Müller-Stich BP, Hackert T, Brenner T, Weigand MA, Uhle F, Schmidt K. Bedside hyperspectral imaging indicates a microcirculatory sepsis pattern - an observational study. Microvasc Res 2021; 136:104164. [PMID: 33831406 DOI: 10.1016/j.mvr.2021.104164] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 03/28/2021] [Accepted: 03/28/2021] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Microcirculatory alterations are key mechanisms in sepsis pathophysiology leading to tissue hypoxia, edema formation, and organ dysfunction. Hyperspectral imaging (HSI) is an emerging imaging technology that uses tissue-light interactions to evaluate biochemical tissue characteristics including tissue oxygenation, hemoglobin content and water content. Currently, clinical data for HSI technologies in critical ill patients are still limited. METHODS AND ANALYSIS TIVITA® Tissue System was used to measure Tissue oxygenation (StO2), Tissue Hemoglobin Index (THI), Near Infrared Perfusion Index (NPI) and Tissue Water Index (TWI) in 25 healthy volunteers and 25 septic patients. HSI measurement sites were the palm, the fingertip, and a suprapatellar knee area. Septic patients were evaluated on admission to the ICU (E), 6 h afterwards (E+6) and three times a day (t3-t9) within a total observation period of 72 h. Primary outcome was the correlation of HSI results with daily SOFA-scores. RESULTS Serial HSI at the three measurement sites in healthy volunteers showed a low mean variance expressing high retest reliability. HSI at E demonstrated significantly lower StO2 and NPI as well as higher TWI at the palm and fingertip in septic patients compared to healthy volunteers. StO2 and TWI showed corresponding results at the suprapatellar knee area. In septic patients, palm and fingertip THI identified survivors (E-t4) and revealed predictivity for 28-day mortality (E). Fingertip StO2 and THI correlated to SOFA-score on day 2. TWI was consistently increased in relation to the TWI range of healthy controls during the observation time. Palm TWI correlated positively with SOFA scores on day 3. DISCUSSION HSI results in septic patients point to a distinctive microcirculatory pattern indicative of reduced skin oxygenation and perfusion quality combined with increased blood pooling and tissue water content. THI might possess risk-stratification properties and TWI could allow tissue edema evaluation in critically ill patients. CONCLUSION HSI technologies could open new perspectives in microcirculatory monitoring by visualizing oxygenation and perfusion quality combined with tissue water content in critically ill patients - a prerequisite for future tissue perfusion guided therapy concepts in intensive care medicine.
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Affiliation(s)
- M Dietrich
- Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany
| | - S Marx
- Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany
| | - M von der Forst
- Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany
| | - T Bruckner
- Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
| | - F C F Schmitt
- Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany
| | - M O Fiedler
- Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany
| | - F Nickel
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - A Studier-Fischer
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - B P Müller-Stich
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - T Hackert
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - T Brenner
- Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany; Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - M A Weigand
- Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany
| | - F Uhle
- Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany
| | - K Schmidt
- Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany; Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
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Guerraty M, Bhargava A, Senarathna J, Mendelson AA, Pathak AP. Advances in translational imaging of the microcirculation. Microcirculation 2021; 28:e12683. [PMID: 33524206 PMCID: PMC8647298 DOI: 10.1111/micc.12683] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 01/18/2021] [Accepted: 01/26/2021] [Indexed: 12/21/2022]
Abstract
The past few decades have seen an explosion in the development and use of methods for imaging the human microcirculation during health and disease. The confluence of innovative imaging technologies, affordable computing power, and economies of scale have ushered in a new era of "translational" imaging that permit us to peer into blood vessels of various organs in the human body. These imaging techniques include near-infrared spectroscopy (NIRS), positron emission tomography (PET), and magnetic resonance imaging (MRI) that are sensitive to microvascular-derived signals, as well as computed tomography (CT), optical imaging, and ultrasound (US) imaging that are capable of directly acquiring images at, or close to microvascular spatial resolution. Collectively, these imaging modalities enable us to characterize the morphological and functional changes in a tissue's microcirculation that are known to accompany the initiation and progression of numerous pathologies. Although there have been significant advances for imaging the microcirculation in preclinical models, this review focuses on developments in the assessment of the microcirculation in patients with optical imaging, NIRS, PET, US, MRI, and CT, to name a few. The goal of this review is to serve as a springboard for exploring the burgeoning role of translational imaging technologies for interrogating the structural and functional status of the microcirculation in humans, and highlight the breadth of current clinical applications. Making the human microcirculation "visible" in vivo to clinicians and researchers alike will facilitate bench-to-bedside discoveries and enhance the diagnosis and management of disease.
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Affiliation(s)
- Marie Guerraty
- Division of Cardiovascular Medicine, Department of
Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA,
USA
| | - Akanksha Bhargava
- Russell H. Morgan Department of Radiology and Radiological
Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Janaka Senarathna
- Russell H. Morgan Department of Radiology and Radiological
Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Asher A. Mendelson
- Department of Medicine, Section of Critical Care, Rady
Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
| | - Arvind P. Pathak
- Russell H. Morgan Department of Radiology and Radiological
Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Department of Biomedical Engineering, The Johns Hopkins
University School of Medicine, Baltimore, MD, USA
- Department of Electrical Engineering, Johns Hopkins
University, Baltimore, MD, USA
- Sidney Kimmel Comprehensive Cancer Center, The Johns
Hopkins University School of Medicine, Baltimore, MD, USA
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Prehospital hemodynamic optimisation is associated with a 30-day mortality decrease in patients with septic shock. Am J Emerg Med 2021; 45:105-111. [PMID: 33684866 DOI: 10.1016/j.ajem.2021.02.060] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Revised: 02/01/2021] [Accepted: 02/24/2021] [Indexed: 12/20/2022] Open
Abstract
INTRODUCTION Septic shock (SS) is characterized by low blood pressure resulting in organ failure and poor prognosis. Among SS treatments, in hospital studies reported a beneficial effect of early hemodynamic resuscitation on mortality rate. This study aims to investigate the relationship between prehospital hemodynamic optimisation and 30-day mortality in patients with SS. METHODS From April 6th, 2016 to December 31th, 2019, patients with SS requiring prehospital Mobile Intensive Care Unit intervention (mICU) were included. Prehospital hemodynamic optimisation was defined as a arterial blood pressure of >65 mmHg, or >75 mmHg if previous hypertension history, at the end of the prehospital stage. RESULTS Three hundred thirty-seven patients were retrospectively analysed. The mean age was 69 ± 15 years, and 226 patients (67%) were male. One hundred and thirty-six patients (40%) had previous hypertension history. Pulmonary, digestive and urinary infections were the suspected cause of the SS in respectively 46%, 23% and 15% of the cases. 30-day overall mortality was 30%. Prehospital hemodynamic optimisation was complete for 204 patients (61%). Cox regression analysis reports a significant association between prehospital hemodynamic optimisation and 30-day mortality (HRa = 0.52 95%CI [0.31-0.86], p = 0.01). CONCLUSION In this study, we report that prehospital hemodynamic optimisation is associated with a decrease in 30-day mortality in patients with SS cared for by a mICU in the prehospital setting. An individualized mean arterial pressure target, based on previous hypertension history, may be considered from the prehospital stage of SS resuscitation.
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Kang C, Cho AR, Lee HJ, Kim HJ, Kim EJ, Jeo S, Hong JM, Moon D. Feasibility study of incident dark-field video microscope for measuring microcirculatory variables in the mouse dorsal skinfold chamber model. Acute Crit Care 2021; 36:29-36. [PMID: 33663037 PMCID: PMC7940105 DOI: 10.4266/acc.2020.00969] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Accepted: 01/09/2021] [Indexed: 11/30/2022] Open
Abstract
Background Despite the importance of microcirculation in organ function, monitoring microcirculation is not a routine practice. With developments in microscopic technology, incident dark field (IDF) microscopy (Cytocam) has allowed visualization of the microcirculation. Dorsal skinfold chamber (DSC) mouse model has been used to investigate microcirculation physiology. By employing Cytocam-IDF imaging with DSC model to assess microcirculatory alteration in lipopolysaccharide (LPS)-induced endotoxemia, we attempted to validate availability of Cytocam-IDF imaging of microcirculation. Methods DSC was implanted in eight BALB/c mice for each group; control and sepsis. Both groups were given 72 hours to recover from surgery. The sepsis group had an additional 24-hour period of recovery post-LPS injection (4 mg/kg). Subsequently, a video of the microcirculation was recorded using Cytocam. Data on microcirculatory variables were obtained. Electron microscopy was implemented using lanthanum fixation to detect endothelial glycocalyx degradation. Results The microcirculatory flow index was significantly lower (control, 2.8±0.3; sepsis, 2.1±0.8; P=0.033) and heterogeneity index was considerably higher (control, 0.10±0.15; sepsis, 0.53±0.48; P=0.044) in the sepsis group than in the control group. Electron microscopy revealed glycocalyx demolishment in the sepsis group. Conclusions Cytocam showed reliable ability for observing changes in the microcirculation under septic conditions in the DSC model. The convenience and good imaging quality and the automatic analysis software available for Cytocam-IDF imaging, along with the ability to perform real-time in vivo experiments in the DSC model, are expected to be helpful in future microcirculation investigations.
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Affiliation(s)
- Christine Kang
- Department of Anesthesia and Pain Medicine, Pusan National University School of Medicine, Yangsan, Korea.,Department of Anesthesia and Pain Medicine, Medical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Ah-Reum Cho
- Department of Anesthesia and Pain Medicine, Pusan National University School of Medicine, Yangsan, Korea.,Department of Anesthesia and Pain Medicine, Medical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Hyeon Jeong Lee
- Department of Anesthesia and Pain Medicine, Pusan National University School of Medicine, Yangsan, Korea.,Department of Anesthesia and Pain Medicine, Medical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Hyae Jin Kim
- Department of Anesthesia and Pain Medicine, Pusan National University School of Medicine, Yangsan, Korea.,Department of Anesthesia and Pain Medicine, Medical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Eun-Jung Kim
- Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Pusan National University, Dental Research Institute, Yangsan, Korea
| | - Soeun Jeo
- Department of Anesthesia and Pain Medicine, Pusan National University School of Medicine, Yangsan, Korea.,Department of Anesthesia and Pain Medicine, Medical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Jeong-Min Hong
- Department of Anesthesia and Pain Medicine, Pusan National University School of Medicine, Yangsan, Korea.,Department of Anesthesia and Pain Medicine, Medical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Daehoan Moon
- Department of Anesthesia and Pain Medicine, Pusan National University School of Medicine, Yangsan, Korea
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Berhouma M, Picart T, Dumot C, Pelissou-Guyotat I, Meyronet D, Ducray F, Honnorat J, Eker O, Guyotat J, Lukaszewicz AC, Cotton F. Alterations of cerebral microcirculation in peritumoral edema: feasibility of in vivo sidestream dark-field imaging in intracranial meningiomas. Neurooncol Adv 2020; 2:vdaa108. [PMID: 33063011 PMCID: PMC7542984 DOI: 10.1093/noajnl/vdaa108] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Background Intracranial meningiomas display a variable amount of peritumoral brain edema (PTBE), which can significantly impact perioperative morbidity. The role of microcirculatory disturbances in the pathogenesis of PTBE is still debated. The aim of this study was to microscopically demonstrate and intraoperatively quantify, for the first time, the alterations to microcirculation in PTBE using sidestream dark-field (SDF) imaging. Methods Adult patients with WHO grade I meningiomas were recruited over a 9-month period and divided into 2 groups depending on the absence (NE group) or the presence (E group) of PTBE. In vivo intraoperative microcirculation imaging was performed in the peritumoral area before and after microsurgical resection. Results Six patients were included in the NE group and 6 in the E group. At the baseline in the NE group, there was a minor decrease in microcirculatory parameters compared to normal reference values, which was probably due to the mass effect. In contrast, microcirculatory parameters in the E group were significantly altered, affecting both vessel density and blood flow values, with a drop of approximately 50% of normal values. Surgical resection resulted in a quasi-normalization of microcirculation parameters in the NE group, whereas in the E group, even if all parameters statistically significantly improved, post-resection values remained considerably inferior to those of the normal reference pattern. Conclusion Our study confirmed significant alterations of microcirculatory parameters in PTBE in meningiomas. Further in vivo SDF imaging studies may explore the possible correlation between the severity of these microcirculatory alterations and the postoperative neurological outcome.
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Affiliation(s)
- Moncef Berhouma
- Department of Neurosurgical Oncology and Vascular Neurosurgery, Pierre Wertheimer Neurological and Neurosurgical Hospital, Hospices Civils de Lyon, Lyon, France.,Creatis Lab, CNRS UMR 5220, INSERM U1206, Lyon 1 University, INSA Lyon, Lyon, France
| | - Thiebaud Picart
- Department of Neurosurgical Oncology and Vascular Neurosurgery, Pierre Wertheimer Neurological and Neurosurgical Hospital, Hospices Civils de Lyon, Lyon, France
| | - Chloe Dumot
- Department of Neurosurgical Oncology and Vascular Neurosurgery, Pierre Wertheimer Neurological and Neurosurgical Hospital, Hospices Civils de Lyon, Lyon, France
| | - Isabelle Pelissou-Guyotat
- Department of Neurosurgical Oncology and Vascular Neurosurgery, Pierre Wertheimer Neurological and Neurosurgical Hospital, Hospices Civils de Lyon, Lyon, France
| | - David Meyronet
- Department of Pathology, Pierre Wertheimer Neurological and Neurosurgical Hospital, Hospices Civils de Lyon, Lyon, France.,Centre de Recherche en Cancérologie de Lyon INSERM U1052 CNRS 5286, Lyon 1 University, Lyon, France
| | - François Ducray
- Department of Neurooncology, Pierre Wertheimer Neurological and Neurosurgical Hospital, Hospices Civils de Lyon, Lyon, France
| | - Jerome Honnorat
- Department of Neurooncology, Pierre Wertheimer Neurological and Neurosurgical Hospital, Hospices Civils de Lyon, Lyon, France
| | - Omer Eker
- Creatis Lab, CNRS UMR 5220, INSERM U1206, Lyon 1 University, INSA Lyon, Lyon, France.,Department of Neuroradiology, Pierre Wertheimer Neurological and Neurosurgical Hospital, Hospices Civils de Lyon, Lyon, France
| | - Jacques Guyotat
- Department of Neurosurgical Oncology and Vascular Neurosurgery, Pierre Wertheimer Neurological and Neurosurgical Hospital, Hospices Civils de Lyon, Lyon, France
| | - Anne-Claire Lukaszewicz
- Department of Neuroanesthesia and Neurocritical Care, Pierre Wertheimer Neurological and Neurosurgical Hospital, Hospices Civils de Lyon, Lyon, France
| | - François Cotton
- Creatis Lab, CNRS UMR 5220, INSERM U1206, Lyon 1 University, INSA Lyon, Lyon, France.,Department of Neuroimaging, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France
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Burzyńska M, Uryga A, Kasprowicz M, Czosnyka M, Dragan B, Kübler A. The relationship between the time of cerebral desaturation episodes and outcome in aneurysmal subarachnoid haemorrhage: a preliminary study. J Clin Monit Comput 2020; 34:705-714. [PMID: 31432383 PMCID: PMC7367903 DOI: 10.1007/s10877-019-00377-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Accepted: 08/14/2019] [Indexed: 12/31/2022]
Abstract
In this preliminary study we investigated the relationship between the time of cerebral desaturation episodes (CDEs), the severity of the haemorrhage, and the short-term outcome in patients with aneurysmal subarachnoid haemorrhage (aSAH). Thirty eight patents diagnosed with aneurysmal subarachnoid haemorrhage were analysed in this study. Regional cerebral oxygenation (rSO2) was assessed using near infrared spectroscopy (NIRS). A CDE was defined as rSO2 < 60% with a duration of at least 30 min. The severity of the aSAH was assessed using the Hunt and Hess scale and the short-term outcome was evaluated utilizing the Glasgow Outcome Scale. CDEs were found in 44% of the group. The total time of the CDEs and the time of the longest CDE on the contralateral side were longer in patients with severe versus moderate aSAH [h:min]: 8:15 (6:26-8:55) versus 1:24 (1:18-4:18), p = 0.038 and 2:05 (2:00-5:19) versus 0:48 (0:44-2:12), p = 0.038. The time of the longest CDE on the ipsilateral side was longer in patients with poor versus good short-term outcome [h:min]: 5:43 (3:05-9:36) versus 1:47 (0:42-2:10), p = 0.018. The logistic regression model for poor short-term outcome included median ABP, the extent of the haemorrhage in the Fisher scale and the time of the longest CDE. We have demonstrated that the time of a CDE is associated with the severity of haemorrhage and short-term outcome in aSAH patients. A NIRS measurement may provide valuable predictive information and could be considered as additional method of neuromonitoring of patients with aSAH.
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Affiliation(s)
- Małgorzata Burzyńska
- Department of Anesthesiology and Intensive Care, Wroclaw Medical University, Wroclaw, Poland
| | - Agnieszka Uryga
- Department of Biomedical Engineering, Faculty of Fundamental Problems of Technology, Wroclaw University of Science and Technology, Wybrzeze Wyspianskiego 27, 50-370, Wroclaw, Poland.
| | - Magdalena Kasprowicz
- Department of Biomedical Engineering, Faculty of Fundamental Problems of Technology, Wroclaw University of Science and Technology, Wybrzeze Wyspianskiego 27, 50-370, Wroclaw, Poland
| | - Marek Czosnyka
- Department of Clinical Neurosciences, Division of Neurosurgery, University of Cambridge, Cambridge, UK
| | - Barbara Dragan
- Department of Anesthesiology and Intensive Care, Wroclaw Medical University, Wroclaw, Poland
| | - Andrzej Kübler
- Department of Anesthesiology and Intensive Care, Wroclaw Medical University, Wroclaw, Poland
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Gueta I, Perach Ovadia Y, Markovits N, Schacham YN, Epsztein A, Loebstein R. Is Pyroglutamic Acid a Prognostic Factor Among Patients with Suspected Infection? A Prospective Cohort Study. Sci Rep 2020; 10:10128. [PMID: 32576856 PMCID: PMC7311518 DOI: 10.1038/s41598-020-66941-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 05/28/2020] [Indexed: 11/09/2022] Open
Abstract
Pyroglutamic acid (PGA) is a compound that accumulates during oxidative stress and hence, elevated levels may be associated with poor prognosis in patients with infection or sepsis. To examine this hypothesis, patients presenting with acute infection were recruited in the emergency department and prospectively followed for 30 days. Sport urine samples were quantified for PGA. Outcomes were mortality and composite outcome of death or organ failure. Thirty two (32%) patients had qSOFA≥2. Median urine PGA was 22.9 (IQR 17.64, 33.53) µmol/mmol creatinine. Four patients demonstrated PGA values ≥ 63 µmol/mmol creatinine. Univariate analysis showed that PGA concentration ≥ 75th percentile (i.e. 33.53 µmol/mmol creatinine) was associated with higher rates of in-hospital mortality (p = 0.041) with similar trend for PGA ≥ 63 µmol/mmol creatinine (p = 0.04). However, multivariate analysis showed that PGA was not associated with worse outcomes, whereas heart rate was associated with both composite outcomes (HR 1.0, p = 0.008 and HR 1.02, p = 0.001 for composite outcome with 30 days and in-hospital mortality, respectively). Among low risk patients, high PGA levels were consistently associated with worse outcomes. In conclusion, urine PGA concentration was not associated with worse outcomes among septic patients. Nevertheless, future studies should evaluate this association in larger cohorts.
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Affiliation(s)
- Itai Gueta
- The institute of Clinical Pharmacology and Toxicology, Sheba Medical Center, Tel Hashomer, Israel. .,Department of Medicine A, Sheba Medical Center, Tel Hashomer, Israel. .,Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | | | - Noa Markovits
- The institute of Clinical Pharmacology and Toxicology, Sheba Medical Center, Tel Hashomer, Israel.,Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Yehoshua N Schacham
- The institute of Clinical Pharmacology and Toxicology, Sheba Medical Center, Tel Hashomer, Israel.,Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Avi Epsztein
- Department of Emergency Medicine, Sheba Medical Center, Tel Hashomer, Israel
| | - Ronen Loebstein
- The institute of Clinical Pharmacology and Toxicology, Sheba Medical Center, Tel Hashomer, Israel.,Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
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Aldecoa C, Llau JV, Nuvials X, Artigas A. Role of albumin in the preservation of endothelial glycocalyx integrity and the microcirculation: a review. Ann Intensive Care 2020; 10:85. [PMID: 32572647 PMCID: PMC7310051 DOI: 10.1186/s13613-020-00697-1] [Citation(s) in RCA: 115] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Accepted: 06/05/2020] [Indexed: 12/11/2022] Open
Abstract
The endothelial glycocalyx comprises a complex layer of membrane-bound proteoglycans, secreted glycosaminoglycans, glycoproteins, glycolipids and bound plasma proteins such as albumin and antithrombin associated with the endothelial surface. The glycocalyx plays an important role in vascular homeostasis, regulating vascular permeability and cell adhesion, and acts as a mechanosensor for hemodynamic shear stresses; it also has antithrombotic and anti-inflammatory functions. Plasma proteins such as albumin are physiologically bound within the glycocalyx, thus contributing to stability of the layer. Albumin is the major determinant of plasma colloid osmotic pressure. In addition, albumin transports sphingosine-1-phosphate which has protective endothelial effects, acts as a free radical scavenger, and has immunomodulatory and anti-inflammatory effects. This review examines the physiological function of the endothelial glycocalyx and the role of human albumin in preserving glycocalyx integrity and the microcirculation.
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Affiliation(s)
- Cesar Aldecoa
- Department of Anaesthesiology and Surgical Critical Care, Hospital Universitario Rio Hortega, c/Dulzaina 2, 47012, Valladolid, Spain
| | - Juan V Llau
- Department of Anaesthesiology and Surgical Critical Care, Hospital Universitario Dr. Peset, Universitat de València, c/Gaspar Aguilar 90, 46017, Valencia, Spain
| | - Xavier Nuvials
- Intensive Care Unit, and SODIR Research Group, Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain
| | - Antonio Artigas
- Critical Care Center, Corporacion Sanitaria Universitaria Parc Tauli, CIBER Enfermedades Respiratorias, Autonomous University of Barcelona, Parc Tauli 1, 08028, Sabadell, Spain.
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Gazmuri RJ, de Gomez CA. From a pressure-guided to a perfusion-centered resuscitation strategy in septic shock: Critical literature review and illustrative case. J Crit Care 2020; 56:294-304. [PMID: 31926637 DOI: 10.1016/j.jcrc.2019.11.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Revised: 07/28/2019] [Accepted: 11/13/2019] [Indexed: 01/15/2023]
Abstract
PURPOSE To support a paradigm shift in the management of septic shock from pressure-guided to perfusion-centered, expected to improve outcome while reducing adverse effects from vasopressor therapy and aggressive fluid resuscitation. MATERIAL AND METHODS Critical review of the literature cited in support of vasopressor use to achieve a predefined mean arterial pressure (MAP) of 65 mmHg and review of pertinent clinical trials and studies enabling deeper understanding of the hemodynamic pathophysiology supportive of a perfusion-centered approach, accompanied by an illustrative case. RESULTS Review of the literature cited by the Surviving Sepsis Campaign revealed lack of controlled clinical trials supporting outcome benefits from vasopressors. Additional literature review revealed adverse effects associated with vasopressors and worsened outcome in some studies. Vasopressors increase MAP primarily by peripheral vasoconstriction and in occasions by a modest increase in cardiac output when using norepinephrine. Thus, achieving the recommended MAP of 65 mmHg using vasopressors should not be presumed indicative that organ perfusion has been restored. It may instead create a false sense of hemodynamic stability hampering shock resolution. CONCLUSIONS We propose focusing the hemodynamic management of septic shock on reversing organ hypoperfusion instead of attaining a predefined MAP target as the key strategy for improving outcome.
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Affiliation(s)
- Raúl J Gazmuri
- Medicine, Physiology & Biophysics, Resuscitation Institute at Rosalind Franklin University of Medicine and Science, Critical Care Medicine and ICU, Captain James A. Lovell Federal Health Care Center, USA.
| | - Cristina Añez de Gomez
- Internal Medicine Physician, Northwestern Medical Group, Northwestern Medicine Lake Forrest Hospital, USA
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Hajibandeh S, Hajibandeh S, Hobbs N, Shah J, Harris M, Watton L, Huq Z, Dalmia S, Malik S, Mansour M. A validated novel preoperative index to predict the extent of intraperitoneal contamination in patients with acute abdominal pathology: A cohort study. J Perioper Pract 2019; 30:221-228. [PMID: 31573381 DOI: 10.1177/1750458919875592] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
AIMS To investigate whether an intraperitoneal contamination index (ICI) derived from combined preoperative levels of C-reactive protein, lactate, neutrophils, lymphocytes and albumin could predict the extent of intraperitoneal contamination in patients with acute abdominal pathology. METHODS Patients aged over 18 who underwent emergency laparotomy for acute abdominal pathology between January 2014 and October 2018 were randomly divided into primary and validation cohorts. The proposed intraperitoneal contamination index was calculated for each patient in each cohort. Receiver operating characteristic curve analysis was performed to determine discrimination of the index and cut-off values of preoperative intraperitoneal contamination index that could predict the extent of intraperitoneal contamination. RESULTS Overall, 468 patients were included in this study; 234 in the primary cohort and 234 in the validation cohort. The analyses identified intraperitoneal contamination index of 24.77 and 24.32 as cut-off values for purulent contamination in the primary cohort (area under the curve (AUC): 0.73, P < 0.0001; sensitivity: 84%, specificity: 60%) and validation cohort (AUC: 0.83, P < 0.0001; sensitivity: 91%, specificity: 69%), respectively. Receiver operating characteristic curve analysis also identified intraperitoneal contamination index of 33.70 and 33.41 as cut-off values for feculent contamination in the primary cohort (AUC: 0.78, P < 0.0001; sensitivity: 87%, specificity: 64%) and validation cohort (AUC: 0.79, P < 0.0001; sensitivity: 86%, specificity: 73%), respectively. CONCLUSIONS As a predictive measure which is derived purely from biomarkers, intraperitoneal contamination index may be accurate enough to predict the extent of intraperitoneal contamination in patients with acute abdominal pathology and to facilitate decision-making together with clinical and radiological findings.
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Affiliation(s)
- Shahab Hajibandeh
- Department of General Surgery, Glan Clwyd Hospital, Rhyl, UK.,Department of General Surgery, North Manchester General Hospital, Northern Care Alliance NHS Group, Manchester, UK
| | - Shahin Hajibandeh
- Department of General Surgery, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK
| | - Nicholas Hobbs
- Department of General Surgery, North Manchester General Hospital, Northern Care Alliance NHS Group, Manchester, UK
| | - Jigar Shah
- Department of General Surgery, North Manchester General Hospital, Northern Care Alliance NHS Group, Manchester, UK
| | - Matthew Harris
- Department of General Surgery, North Manchester General Hospital, Northern Care Alliance NHS Group, Manchester, UK
| | - Leo Watton
- Department of General Surgery, North Manchester General Hospital, Northern Care Alliance NHS Group, Manchester, UK
| | - Zahirul Huq
- Department of General Surgery, North Manchester General Hospital, Northern Care Alliance NHS Group, Manchester, UK
| | - Sanjay Dalmia
- Department of General Surgery, North Manchester General Hospital, Northern Care Alliance NHS Group, Manchester, UK
| | - Sohail Malik
- Department of General Surgery, North Manchester General Hospital, Northern Care Alliance NHS Group, Manchester, UK
| | - Moustafa Mansour
- Department of General Surgery, North Manchester General Hospital, Northern Care Alliance NHS Group, Manchester, UK
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Kuang L, Zhu Y, Zhang J, Wu Y, Tian K, Chen X, Xue M, Tzang FC, Lau B, Wong BL, Liu L, Li T. A novel cross-linked haemoglobin-based oxygen carrier is beneficial to sepsis in rats. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2019; 47:1496-1504. [PMID: 30983419 DOI: 10.1080/21691401.2019.1602049] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Pathological hypoxia-induced organ dysfunction contributes to the high mortality of sepsis. Because of the microcirculation dysfunction following severe sepsis, it is difficult for erythrocytes to transport oxygen to hypoxic tissues. Haemoglobin-based oxygen carriers (HBOCs) are capable of delivering oxygen to hypoxic tissues. The aim of this study is to observe the potential benefits of a novel bovine-derived, non-polymerized, cell-free HBOC solution, YQ23, on sepsis in rats. Cecum ligation and puncture was performed to induce sepsis in Sprague-Dawley rats. Effects of Lactate Ringer's solution (LR), YQ23, and whole blood on oxygen delivery and consumption, mitochondrial function, organ protection and animal survival were observed. LR failed to restore oxygen delivery and the therapeutic effects were limited, whereas low dosage of YQ23 and whole blood significantly increased the tissue oxygen delivery and consumption, improved the mitochondrial function of heart, liver, kidney and intestine, prevented the vital organs injuries and improved the animal survival. The effects of 0.15 g·kg-1 YQ23 resembled that of the whole blood. In addition, YQ23 did not induce renal toxicity, severe oxidative effect and acute vasoconstriction. Thus, YQ23 is a safe and effective resuscitation fluid for sepsis.
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Affiliation(s)
- Lei Kuang
- a State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital , Third Military Medical University (Army Medical University) , Chongqing , P.R. China
| | - Yu Zhu
- a State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital , Third Military Medical University (Army Medical University) , Chongqing , P.R. China
| | - Jie Zhang
- a State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital , Third Military Medical University (Army Medical University) , Chongqing , P.R. China
| | - Yue Wu
- a State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital , Third Military Medical University (Army Medical University) , Chongqing , P.R. China
| | - Kunlun Tian
- a State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital , Third Military Medical University (Army Medical University) , Chongqing , P.R. China
| | - Xiangyun Chen
- a State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital , Third Military Medical University (Army Medical University) , Chongqing , P.R. China
| | - Mingying Xue
- a State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital , Third Military Medical University (Army Medical University) , Chongqing , P.R. China
| | | | - Billi Lau
- b New B Innovation Limited , Kowloon Bay , Hong Kong
| | - Bing Lou Wong
- b New B Innovation Limited , Kowloon Bay , Hong Kong
| | - Liangming Liu
- a State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital , Third Military Medical University (Army Medical University) , Chongqing , P.R. China
| | - Tao Li
- a State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital , Third Military Medical University (Army Medical University) , Chongqing , P.R. China
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Nassar B, Mallat J. Usefulness of venous-to-arterial partial pressure of CO 2 difference to assess oxygen supply to demand adequacy: effects of dobutamine. J Thorac Dis 2019; 11:S1574-S1578. [PMID: 31388463 PMCID: PMC6642911 DOI: 10.21037/jtd.2019.04.85] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Accepted: 04/16/2019] [Indexed: 12/11/2022]
Abstract
The central venous O2 saturation value and lactic acid levels are part of the diagnostic and therapeutic work up of patients in shock. These usual indicators of tissue hypoxia don't fully describe the adequacy of tissue perfusion. There is ample evidence that supplementing this data with the venous-to-arterial partial pressure of CO2 (PCO2) difference (ΔPCO2) complements the clinician's tools when treating patients with shock. Based on a modified Fick equation as it applies to CO2, in patients in a steady state, the ΔPCO2 reflects the cardiac output (CO). This observation has been shown to be of clinical value in resuscitating patients in shock. Moreover, the ΔPCO2 can be used to titrate inotropes, and differentiate the hemodynamic from the metabolic effect of dobutamine.
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Affiliation(s)
- Boulos Nassar
- Department of Critical Care Medicine, Critical Care Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE
- Pulmonary and Critical Care Division, University of Iowa Hospitals and Clinics, Iowa City, IA, USA
| | - Jihad Mallat
- Department of Critical Care Medicine, Critical Care Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE
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Kristof K, Büttner B, Grimm A, Mewes C, Schmack B, Popov AF, Ghadimi M, Beissbarth T, Hinz J, Bergmann I, Mansur A. Anaemia requiring red blood cell transfusion is associated with unfavourable 90-day survival in surgical patients with sepsis. BMC Res Notes 2018; 11:879. [PMID: 30537993 PMCID: PMC6290543 DOI: 10.1186/s13104-018-3988-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Accepted: 12/05/2018] [Indexed: 12/26/2022] Open
Abstract
Objective The mortality associated with sepsis remains unacceptably high, despite modern high-quality intensive care. Based on the results from previous studies, anaemia and its management in patients with sepsis appear to impact outcomes; however, the transfusion policy is still being debated, and the ideal approach may be extremely specific to the individual. This study aimed to investigate the long-term impact of anaemia requiring red blood cell (RBC) transfusion on mortality and disease severity in patients with sepsis. We studied a general surgical intensive care unit (ICU) population, excluding cardiac surgery patients. 435 patients were enrolled in this observational study between 2012 and 2016. Results Patients who received RBC transfusion between 28 days before and 28 days after the development of sepsis (n = 302) exhibited a significantly higher 90-day mortality rate (34.1% vs 19.6%; P = 0.004, Kaplan–Meier analysis). This association remained significant after adjusting for confounders in the multivariate Cox regression analysis (hazard ratio 1.68; 95% confidence interval 1.03–2.73; P = 0.035). Patients who received transfusions also showed significantly higher morbidity scores, such as SOFA scores, and ICU lengths of stay compared to patients without transfusions (n = 133). Our results indicate that anaemia and RBC transfusion are associated with unfavourable outcomes in patients with sepsis. Electronic supplementary material The online version of this article (10.1186/s13104-018-3988-z) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Katalin Kristof
- Department of Anesthesiology, University Medical Center, Georg August University, Goettingen, Germany
| | - Benedikt Büttner
- Department of Anesthesiology, University Medical Center, Georg August University, Goettingen, Germany
| | - Anna Grimm
- Department of Anesthesiology, University Medical Center, Georg August University, Goettingen, Germany
| | - Caspar Mewes
- Department of Anesthesiology, University Medical Center, Georg August University, Goettingen, Germany
| | - Bastian Schmack
- Department of Cardiac Surgery, University Hospital, Ruprecht Karls University, Heidelberg, Germany
| | - Aron Frederik Popov
- Department of Thoracic and Cardiovascular Surgery, University Medical Center, Goethe University, Frankfurt, Germany
| | - Michael Ghadimi
- Department of General, Visceral and Pediatric Surgery, University Medical Center, Georg August University, Goettingen, Germany
| | - Tim Beissbarth
- Department of Medical Statistics, University Medical Center, Georg August University, Goettingen, Germany
| | - José Hinz
- Department of Anesthesiology, University Medical Center, Georg August University, Goettingen, Germany
| | - Ingo Bergmann
- Department of Anesthesiology, University Medical Center, Georg August University, Goettingen, Germany
| | - Ashham Mansur
- Department of Anesthesiology, University Medical Center, Georg August University, Goettingen, Germany.
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Skin mottling score and capillary refill time to assess mortality of septic shock since pre-hospital setting. Am J Emerg Med 2018; 37:664-671. [PMID: 30001815 DOI: 10.1016/j.ajem.2018.07.010] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2018] [Accepted: 07/05/2018] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVES The early identification of septic shock patients at high risk of poor outcome is essential to early initiate optimal treatments and to decide on hospital admission. Biomarkers are often used to evaluate the severity. In prehospital settings, the availability of biomarkers, such as lactate, is restricted. In this context, clinical tools such as skin mottling score (SMS) and capillary refill time (CRT) are more suitable. In this study, we describe prehospital SMS and CRT's ability to predict mortality of patients with septic shock initially cared in the prehospital setting by a mobile intensive care unit. METHODS Patients with septic shock who received prehospital medical care admitted to the intensive care unit were retrospectively analyzed. RESULTS Sixty-three patients were included. The origin of sepsis was mainly pulmonary (67%). Overall mortality reached 36%. No significant difference was observed in the duration of prehospital medical care between alive and deceased patients. Mean prehospital value of SMS was 3 ± 2 and mean prehospital value of CRT was 5 ± 1 s. A significant association was found between mortality and prehospital SMS (p = 0.02, OR[CI95] = 1.50 [1.08-2.15]) and prehospital CRT (p = 0.04, OR[CI95] = 1.53 [1.04-2.37]). After adjusting for confounding factors using propensity score, the relative risk of death was 6.58 for SMS > 2 and 2.03 for CRT > 4 s. CONCLUSION In this study, we report an association between prehospital SMS and CRT, and mortality of patients with septic shock. SMS and CRT are simple tools that could be used to optimize the triage and to decide early intensive care admission.
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Bennett VA, Vidouris A, Cecconi M. Effects of Fluids on the Macro- and Microcirculations. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2018; 22:74. [PMID: 29558989 PMCID: PMC5861604 DOI: 10.1186/s13054-018-1993-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2018. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2018. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.
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Affiliation(s)
- Victoria A Bennett
- Department of Intensive Care Medicine, St George's University Hospital NHS Foundation Trust, London, UK.
| | - Alexander Vidouris
- Department of Intensive Care Medicine, St George's University Hospital NHS Foundation Trust, London, UK
| | - Maurizio Cecconi
- Department of Intensive Care Medicine, St George's University Hospital NHS Foundation Trust, London, UK
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