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1
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Song H, Liao Y, Hu H, Wan Q. Mean arterial pressure at the initiation of continuous renal replacement therapy as a prognostic indicator in patients with acute kidney injury. Ren Fail 2025; 47:2448582. [PMID: 39763014 PMCID: PMC11721759 DOI: 10.1080/0886022x.2024.2448582] [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: 06/11/2024] [Revised: 12/24/2024] [Accepted: 12/26/2024] [Indexed: 01/12/2025] Open
Abstract
BACKGROUND Acute kidney injury (AKI) is a common complication in critically ill patients, with approximately 5% requiring continuous renal replacement therapy (CRRT). This study investigated the relationship between mean arterial pressure (MAP) and 28- and 90-day mortality in critically ill AKI patients treated with CRRT. METHODS This secondary analysis of a bicenter, retrospective, observational study included patients with AKI who were treated with CRRT from January 2009 to September 2016. Mortality at 28 and 90 days post-CRRT initiation was analyzed using multivariate regression, generalized additive models, smooth curve fitting, and sensitivity analyses. RESULTS A total of 1,142 patients were included, with 28-day and 90-day mortality rates of 62.1% and 71.8%, respectively. In multivariable-adjusted Cox models, MAP was inversely correlated with the risk of 28-day and 90-day mortality after adjusting for covariates. Hazard ratios (HRs) were calculated per 1 mmHg increment of MAP: adjusted HR for 28-day mortality 0.985 (p < 0.00001) and for 90-day mortality 0.987 (p = 0.00002). The adjusted HRs for 28-day and 90-day mortality in patients in the highest tertile of MAP compared with those in the lowest tertile were 0.682 (95% CI 0.543-0.857) and 0.730 (95% CI 0.592-0.899), respectively. Patients were grouped using MAP thresholds of <65 mmHg, 65-71.85 mmHg, and ≥71.85 mmHg, with similar results observed. Sensitivity analyses confirmed the inverse relationship between higher MAP before CRRT and lower mortality. CONCLUSION The higher the MAP before CRRT is, the lower the 28- and 90-day mortality of critically ill patients with AKI who are treated with CRRT.
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Affiliation(s)
- Haiying Song
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong Province, China
- Department of Nephrology, Shenzhen University Health Science Center, Shenzhen, Guangdong Province, China
| | - Yuheng Liao
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong Province, China
- Department of Nephrology, Shenzhen University Health Science Center, Shenzhen, Guangdong Province, China
| | - Haofei Hu
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong Province, China
- Department of Nephrology, Shenzhen University Health Science Center, Shenzhen, Guangdong Province, China
| | - Qijun Wan
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong Province, China
- Department of Nephrology, Shenzhen University Health Science Center, Shenzhen, Guangdong Province, China
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Chen Q, Li W, Wang Y, Chen X, He D, Liu M, Yuan J, Xiao C, Li Q, Chen L, Shen F. Investigating the Association Between Mean Arterial Pressure on 28-Day Mortality Risk in Patients With Sepsis: Retrospective Cohort Study Based on the MIMIC-IV Database. Interact J Med Res 2025; 14:e63291. [PMID: 40042975 PMCID: PMC11931324 DOI: 10.2196/63291] [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: 06/15/2024] [Revised: 01/02/2025] [Accepted: 01/28/2025] [Indexed: 03/26/2025] Open
Abstract
Background Sepsis is a globally recognized health issue that continues to contribute significantly to mortality and morbidity in intensive care units (ICUs). The association between mean arterial pressure (MAP) and prognosis among patients with patients is yet to be demonstrated. Objective The aim of this study was to explore the association between MAP and 28-day mortality in ICU patients with sepsis using data from a large, multicenter database. Methods This is a retrospective cohort study. We extracted data of 35,010 patients with sepsis from the MIMIC-IV (Medical Information Mart for Intensive Care) database between 2008 and 2019, according to the Sepsis 3.0 diagnostic criteria. The MAP was calculated as the average of the highest and lowest readings within the first 24 hours of ICU admission, and patients were divided into 4 groups based on the mean MAP, using the quadruple classification approach. Other worst-case indications from the first 24 hours of ICU admission, such as vital signs, severity of illness scores, laboratory indicators, and therapies, were also gathered as baseline data. The independent effects of MAP on 28-day mortality were explored using binary logistic regression and a two-piecewise linear model, with MAP as the exposure and 28-day mortality as the outcome variables, respectively. To address the nonlinearity relationship, curve fitting and a threshold effect analysis were performed. Results A total of 34,981 patients with sepsis were included in the final analysis, the mean age was 66.67 (SD 16.01) years, and the 28-day mortality rate was 16.27% (5691/34,981). The generalized additive model and smoothed curve fitting found a U-shaped relationship between MAP and 28-day mortality in these patients. The recursive algorithm determined the low and high inflection points as 70 mm and 82 mm Hg, respectively. Our data demonstrated that MAP was negatively associated with 28-day mortality in the range of 34.05 mm Hg-69.34 mm Hg (odds ratio [OR] 0.93, 95% CI 0.92-0.94; P<.001); however, once the MAP exceeded 82 mm Hg, a positive association existed between MAP and 28-day mortality of patients with sepsis (OR 1.01; 95% CI 1.01-1.02, P=.002). Conclusions There is a U-shaped association between MAP and the probability of 28-day mortality in patients with sepsis. Both the lower and higher MAP were related with a higher risk of mortality in patients with sepsis. These patients have a decreased risk of mortality when their MAP remains between 70 and 82 mm Hg.
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Affiliation(s)
- Qimin Chen
- Department of Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University, Beijing Road No. 8, Yunyan District, Guiyang, Guizhou Province, 550001, China, 86 13511999117
| | - Wei Li
- Department of Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University, Beijing Road No. 8, Yunyan District, Guiyang, Guizhou Province, 550001, China, 86 13511999117
| | - Ying Wang
- Department of Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University, Beijing Road No. 8, Yunyan District, Guiyang, Guizhou Province, 550001, China, 86 13511999117
| | - Xianjun Chen
- Department of Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University, Beijing Road No. 8, Yunyan District, Guiyang, Guizhou Province, 550001, China, 86 13511999117
| | - Dehua He
- Department of Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University, Beijing Road No. 8, Yunyan District, Guiyang, Guizhou Province, 550001, China, 86 13511999117
| | - Ming Liu
- Department of Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University, Beijing Road No. 8, Yunyan District, Guiyang, Guizhou Province, 550001, China, 86 13511999117
| | - Jia Yuan
- Department of Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University, Beijing Road No. 8, Yunyan District, Guiyang, Guizhou Province, 550001, China, 86 13511999117
| | - Chuan Xiao
- Department of Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University, Beijing Road No. 8, Yunyan District, Guiyang, Guizhou Province, 550001, China, 86 13511999117
| | - Qing Li
- Department of Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University, Beijing Road No. 8, Yunyan District, Guiyang, Guizhou Province, 550001, China, 86 13511999117
| | - Lu Chen
- Clinical Trials Centre, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Feng Shen
- Department of Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University, Beijing Road No. 8, Yunyan District, Guiyang, Guizhou Province, 550001, China, 86 13511999117
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Kim JS, Ivanovic S, Davison D, Bheem R, Wu M, Sweeney B, Shaykhinurov E, Yamane D. Midline Catheters as an Alternative for Central Venous Catheters in Venous Oxygen Saturation Monitoring: A Single Center Experience. J Intensive Care Med 2025; 40:47-53. [PMID: 39043372 DOI: 10.1177/08850666241265190] [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] [Indexed: 07/25/2024]
Abstract
BACKGROUND Central venous oxygen saturation (ScvO2) obtained from a central venous catheter (CVC) is often used to approximate oxygen delivery in critically ill patients. Despite their importance in administering medications and monitoring oxygen delivery, the use of CVCs can be associated with significant complications. Midline catheters are inserted via a peripheral vein above the antecubital fossa and provide a safe alternative to CVCs. This study aimed to determine the equivalence of ScvO2 and midline catheter oxygen saturation (SmO2) in critically ill patients. METHODS This was a single-center observational study of critically ill adult patients who had concurrently placed CVCs (internal jugular and subclavian) and midline catheters as part of standard ICU care. Venous oxygen saturation and lactate levels were measured from both catheters using the Abbott point-of-care i-STAT analyzer. Demographic and ICU admission data were collected. Continuous variables were compared using the paired t-test. Pearson's correlation was used to evaluate the linear correlation between ScvO2 and SmO2. The systematic error (bias) was calculated using Bland-Altman analysis. Receiver operating characteristic curves were constructed to evaluate the sensitivities and specificities for different values of SmO2 to predict ScvO2. RESULTS Forty-eight patients (n = 48) were enrolled in the study. The mean ScvO2 and SmO2 were 65.5% +/- 11.2% and 62.7% +/- 17.6% respectively (p = 0.1197). In the Bland-Altman analysis, the mean bias between ScvO2 and SmO2 was 2.8% +/- 12.3% with 95% limits of agreement of -21.3% to 26.9%. More than 60% of the ScvO2 and SmO2 values diverged by ≥ 5%. CONCLUSIONS The difference between the mean SmO2 and ScvO2 was not statistically significant and the mean bias between SmO2 and ScvO2 is low. Despite this, the substantially large standard deviation and limits of agreement preclude the use of SmO2 as a direct surrogate of ScvO2.
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Affiliation(s)
- Justin S Kim
- Department of Anesthesia and Critical Care Medicine, George Washington University, Washington, DC, USA
| | - Sasa Ivanovic
- Department of Internal Medicine, Section of Pulmonary, Critical Care, & Sleep Medicine, Yale University School of Medicine, New Haven, CT, USA
- Department of Pulmonary & Critical Care Medicine, Yale New Haven Hospital, New Haven, CT, USA
| | - Danielle Davison
- Department of Anesthesia and Critical Care Medicine, George Washington University, Washington, DC, USA
| | - Rishika Bheem
- School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA
| | - Maria Wu
- School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA
| | - Brendan Sweeney
- School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA
| | - Eduard Shaykhinurov
- Department of Anesthesia and Critical Care Medicine, George Washington University, Washington, DC, USA
| | - David Yamane
- Department of Anesthesia and Critical Care Medicine, George Washington University, Washington, DC, USA
- Department of Emergency Medicine, George Washington University, Washington, DC, USA
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Ahn C, Yu G, Shin TG, Cho Y, Park S, Suh GY. Comparison of Early and Late Norepinephrine Administration in Patients With Septic Shock: A Systematic Review and Meta-Analysis. Chest 2024; 166:1417-1430. [PMID: 38972348 DOI: 10.1016/j.chest.2024.05.042] [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: 01/12/2024] [Revised: 05/15/2024] [Accepted: 05/16/2024] [Indexed: 07/09/2024] Open
Abstract
BACKGROUND Vasopressor administration at an appropriate time is crucial, but the optimal timing remains controversial. RESEARCH QUESTION Does early vs late norepinephrine administration impact the prognosis of septic shock? STUDY DESIGN AND METHODS Searches were conducted in PubMed, EMBASE, the Cochrane Library, and KMbase databases. We included studies of adults with sepsis and categorized patients into an early and late norepinephrine group according to specific time points or differences in norepinephrine use protocols. The primary outcome was overall mortality. The secondary outcomes included length of stay in the ICU, days free from ventilator use, days free from renal replacement therapy, days free from vasopressor use, adverse events, and total fluid volume. RESULTS Twelve studies (four randomized controlled trials [RCTs] and eight observational studies) comprising 7,281 patients were analyzed. For overall mortality, no significant difference was found between the early norepinephrine group and late norepinephrine group in RCTs (OR, 0.70; 95% CI, 0.41-1.19) or observational studies (OR, 0.83; 95% CI, 0.54-1.29). In the two RCTs without a restrictive fluid strategy that prioritized vasopressors and lower IV fluid volumes, the early norepinephrine group showed significantly lower mortality than the late norepinephrine group (OR, 0.49; 95%, CI, 0.25-0.96). The early norepinephrine group demonstrated more mechanical ventilator-free days in observational studies (mean difference, 4.06; 95% CI, 2.82-5.30). The incidence of pulmonary edema was lower in the early norepinephrine group in the three RCTs that reported this outcome (OR, 0.43; 95% CI, 0.25-0.74). No differences were found in the other secondary outcomes. INTERPRETATION Overall mortality did not differ significantly between early and late norepinephrine administration for septic shock. However, early norepinephrine administration seemed to reduce pulmonary edema incidence, and mortality improvement was observed in studies without fluid restriction interventions, favoring early norepinephrine use.
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Affiliation(s)
- Chiwon Ahn
- Department of Emergency Medicine, College of Medicine, Chung-Ang University, Seoul, South Korea
| | - Gina Yu
- Department of Emergency Medicine, University of Yonsei College of Medicine, Seoul, South Korea
| | - Tae Gun Shin
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
| | - Youngsuk Cho
- Department of Emergency Medicine, Kangdong Sacred Heart Hospital, Hallym University, Seoul, South Korea
| | - Sunghoon Park
- Department of Pulmonary, Allergy and Critical Care Medicine, Hallym University Sacred Heart Hospital, Anyang, South Korea
| | - Gee Young Suh
- Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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Ferreira Alves G, Oliveira JG, Nakashima MA, Delfrate G, Sordi R, Assreuy J, da Silva-Santos JE, Collino M, Fernandes D. Cardiovascular effects of Roflumilast during sepsis: Risks or benefits? Eur J Pharmacol 2024; 983:177015. [PMID: 39332796 DOI: 10.1016/j.ejphar.2024.177015] [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: 05/28/2024] [Revised: 09/06/2024] [Accepted: 09/25/2024] [Indexed: 09/29/2024]
Abstract
BACKGROUND Phosphodiesterase-4 (PDE4) is responsible for terminating cyclic adenosine monophosphate (cAMP) signalling. PDE4 inhibitors, such as roflumilast (RFM), have anti-inflammatory activity and have been studied in inflammation-induced tissue damage in sepsis. However, the role of RFM on cardiovascular derangements induced by sepsis is still unknown. Thus, we aimed to evaluate the potential effects of RFM on cardiovascular collapse and multiorgan damage caused by sepsis. METHODS Sepsis was induced by cecal ligation and puncture (CLP) in male rats. Six hours after the CLP or sham procedure, animals were randomly assigned to receive either RFM (0.3 mg/kg) or vehicle subcutaneously, and cardiovascular parameters were assessed 24 h after the surgery and organ/plasma samples were collected for further analyses. RESULTS Sepsis induced hypotension, tachycardia, reduced renal blood flow (RBF) and hyporeactivity to vasoconstrictors both in vivo and ex vivo. RFM treatment increased systemic cAMP levels and RBF. RFM also attenuated hypoperfusion and liver damage induced by CLP. Furthermore, RFM reduced systemic nitric oxide (NO) levels in septic rats, while there were no changes in hepatic NOS-2 expression. Nevertheless, RFM exacerbated sepsis-induced hypotension and tachycardia without ameliorating vascular hyporeactivity. CONCLUSION Our data show that PDE-4 inhibition protects septic rats from hepatic injury and improves renal perfusion. However, RFM worsened hemodynamic parameters and showed no protection against sepsis-induced cardiovascular dysfunction and mortality. Thus, despite the anti-inflammatory benefits of RFM, its application in sepsis should be approached cautiously.
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Affiliation(s)
- Gustavo Ferreira Alves
- Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, Brazil; Department of Neurosciences "Rita Levi Montalcini", University of Turin, Turin, Italy
| | | | | | - Gabrielle Delfrate
- Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, Brazil
| | - Regina Sordi
- Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, Brazil
| | - Jamil Assreuy
- Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, Brazil
| | | | - Massimo Collino
- Department of Neurosciences "Rita Levi Montalcini", University of Turin, Turin, Italy
| | - Daniel Fernandes
- Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, Brazil.
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Orbegozo D, Stringari G, Damazio R, De Backer D, Vincent JL, Creteur J. Altered Microvascular Reactivity During a Skin Thermal Challenge Is Associated With Organ Dysfunction and Slow Recovery After Cardiac Surgery. J Cardiothorac Vasc Anesth 2024; 38:2684-2692. [PMID: 39034163 DOI: 10.1053/j.jvca.2024.06.045] [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: 03/03/2024] [Revised: 06/26/2024] [Accepted: 06/30/2024] [Indexed: 07/23/2024]
Abstract
OBJECTIVES To assess microvascular reactivity during a skin thermal challenge early post-cardiac surgery and its association with outcomes. DESIGN Noninvasive physiological study. SETTING Thirty-five-bed department of intensive care. PARTICIPANTS Patients admitted to the intensive care unit post-cardiac surgery. INTERVENTIONS Thermal challenge. MEASUREMENTS AND MAIN RESULTS A total of 46 patients were included; 14 needed vasoactive or ventilatory support for at least 48 hours (slow recovery), and 32 had a more rapid recovery. Skin blood flow (SBF) was measured on the anterior proximal forearm using skin laser Doppler. A thermal challenge was performed by abruptly increasing local skin temperature from 37°C to 43°C while monitoring SBF. The ratio between SBFs at 43°C and 37°C was calculated to measure microvascular reactivity. SBF at 37°C was not significantly different in patients with a slow recovery and those with a rapid recovery, but SBF after 9 minutes at 43°C was lower (48.5 [17.3-69.0] v 85.1 [45.2-125.7], p < 0.01), resulting in a lower SBF ratio (2.8 [1.5-4.7] v 4.8 [3.7-7.8], p < 0.01). Patients with lower SBF ratios were more likely to have dysfunction of at least one organ (assessed using the sequential organ dysfunction score) 48 hours post-cardiac surgery than those with higher ratios: 88% versus 40% versus 27% (p < 0.01), respectively, for the lowest, middle, and highest tertiles of SBF ratio. In multivariable analysis, a lower SBF ratio was an independent risk factor for slow recovery. CONCLUSIONS Early alterations in microvascular reactivity, evaluated by a skin thermal challenge, are correlated with organ dysfunction. These observations may help in the development of new, simple, noninvasive monitoring systems in postoperative patients.
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Affiliation(s)
- Diego Orbegozo
- Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Gianni Stringari
- Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Rafael Damazio
- Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Daniel De Backer
- Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Jean-Louis Vincent
- Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Jacques Creteur
- Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium.
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Bruno RR, Schemmelmann M, Hornemann J, Moecke HME, Demirtas F, Palici L, Marinova R, Kanschik D, Binnebößel S, Spomer A, Guidet B, Leaver S, Flaatten H, Szczeklik W, Mikiewicz M, De Lange DW, Quenard S, Beil M, Kelm M, Jung C. Sublingual microcirculatory assessment on admission independently predicts the outcome of old intensive care patients suffering from shock. Sci Rep 2024; 14:25668. [PMID: 39463395 PMCID: PMC11514226 DOI: 10.1038/s41598-024-77357-y] [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] [Received: 06/03/2024] [Accepted: 10/22/2024] [Indexed: 10/29/2024] Open
Abstract
Shock is a life-threatening condition. This study evaluated if sublingual microcirculatory perfusion on admission is associated with 30-day mortality in older intensive care unit (ICU) shock patients. This trial prospectively recruited ICU patients (≥ 80 years old) with arterial lactate above 2 mmol/L, requiring vasopressors despite adequate fluid resuscitation, regardless of shock cause. All patients received sequential sublingual measurements on ICU admission (± 4 h) and 24 (± 4) hours later. The primary endpoint was 30-day mortality. From September 4th, 2022, to May 30th, 2023, 271 patients were screened, and 44 included. Patients were categorized based on the median percentage of perfused small vessels (sPPV) into those with impaired and sustained microcirculation. 71% of videos were of good or acceptable quality without safety issues. Patients with impaired microcirculation had significantly shorter ICU and hospital stays (p = 0.015 and p = 0.019) and higher 30-day mortality (90.0% vs. 62.5%, p = 0.036). Cox regression confirmed the independent association of impaired microcirculation with 30-day mortality (adjusted hazard ratio 3.245 (95% CI 1.178 to 8.943, p = 0.023). Measuring sublingual microcirculation in critically ill older patients with shock on ICU admission is safe, feasible, and provides independent prognostic information about outcomes.Trial registration NCT04169204.
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Affiliation(s)
- Raphael Romano Bruno
- Medical Faculty, Department of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany
| | - Mara Schemmelmann
- Medical Faculty, Department of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany
| | - Johanna Hornemann
- Medical Faculty, Department of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany
| | - Helene Mathilde Emilie Moecke
- Medical Faculty, Department of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany
| | - Filiz Demirtas
- Medical Faculty, Department of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany
| | - Lina Palici
- Medical Faculty, Department of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany
| | - Radost Marinova
- Medical Faculty, Department of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany
| | - Dominika Kanschik
- Medical Faculty, Department of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany
| | - Stephan Binnebößel
- Medical Faculty, Department of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany
| | - Armin Spomer
- Medical Faculty, Department of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany
| | - Bertrand Guidet
- Equipe: épidémiologie hospitalière qualité et organisation des soins, Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, 75012, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, service de réanimation médicale, Paris, 75012, France
| | - Susannah Leaver
- General Intensive care, St George's University Hospitals NHS Foundation trust, London, UK
| | - Hans Flaatten
- Department of Clinical Medicine, Department of Anaestesia and Intensive Care, University of Bergen, Haukeland University Hospital, Bergen, Norway
| | - Wojciech Szczeklik
- Centre for Intensive Care and Perioperative Medicine, Jagiellonian University Medical College, Krakow, Poland
| | - Maciej Mikiewicz
- Centre for Intensive Care and Perioperative Medicine, Jagiellonian University Medical College, Krakow, Poland
| | - Dylan W De Lange
- Department of Intensive Care Medicine, University Medical Center, University Utrecht, Utrecht, the Netherlands
| | - Stanislas Quenard
- Equipe: épidémiologie hospitalière qualité et organisation des soins, Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, 75012, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, service de réanimation médicale, Paris, 75012, France
| | - Michael Beil
- General and Medical Intensive Care Units, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Malte Kelm
- Medical Faculty, Department of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany
- CARID (Cardiovascular Research Institute Düsseldorf), Duesseldorf, Germany
| | - Christian Jung
- Medical Faculty, Department of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany.
- CARID (Cardiovascular Research Institute Düsseldorf), Duesseldorf, Germany.
- Division of Cardiology, Pulmonology, and Vascular Medicine, University Duesseldorf, Moorenstraße 5, 40225, Duesseldorf, Germany.
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8
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Jia X, Zhang H, Sui W, Zhao A, Ma K. Association between average mean arterial pressure and 30-day mortality in critically ill patients with sepsis and primary hypertension: a retrospective analysis. Sci Rep 2024; 14:20640. [PMID: 39232111 PMCID: PMC11374803 DOI: 10.1038/s41598-024-71146-3] [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: 03/27/2024] [Accepted: 08/26/2024] [Indexed: 09/06/2024] Open
Abstract
Sepsis and hypertension pose significant health risks, yet the optimal mean arterial pressure (MAP) target for resuscitation remains uncertain. This study investigates the association between average MAP (a-MAP) within the initial 24 h of intensive care unit admission and clinical outcomes in patients with sepsis and primary hypertension using the Medical Information Mart for Intensive Care (MIMIC) IV database. Multivariable Cox regression assessed the association between a-MAP and 30-day mortality. Kaplan-Meier and log-rank analyses constructed survival curves, while restricted cubic splines (RCS) illustrated the nonlinear relationship between a-MAP and 30-day mortality. Subgroup analyses ensured robustness. The study involved 8,810 patients. Adjusted hazard ratios for 30-day mortality in the T1 group (< 73 mmHg) and T3 group (≥ 80 mmHg) compared to the T2 group (73-80 mmHg) were 1.25 (95% CI 1.09-1.43, P = 0.001) and 1.44 (95% CI 1.25-1.66, P < 0.001), respectively. RCS revealed a U-shaped relationship (non-linearity: P < 0.001). Kaplan-Meier curves demonstrated significant differences (P < 0.0001). Subgroup analysis showed no significant interactions. Maintaining an a-MAP of 73 to 80 mmHg may be associated with a reduction in 30-day mortality. Further validation through prospective randomized controlled trials is warranted.
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Affiliation(s)
- Xinhua Jia
- Department of Critical Care Medicine, Dezhou People's Hospital, Shandong, China
| | - Hongyang Zhang
- Department of Critical Care Medicine, Dezhou People's Hospital, Shandong, China
| | - Weinan Sui
- Department of Critical Care Medicine, Dezhou People's Hospital, Shandong, China
| | - Aichao Zhao
- Department of Critical Care Medicine, Dezhou People's Hospital, Shandong, China.
| | - Kun Ma
- Department of Critical Care Medicine, Dezhou People's Hospital, Shandong, China.
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9
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Ferreira Alves G, Aimaretti E, da Silveira Hahmeyer ML, Einaudi G, Porchietto E, Rubeo C, Marzani E, Aragno M, da Silva-Santos JE, Cifani C, Fernandes D, Collino M. Pharmacological inhibition of CK2 by silmitasertib mitigates sepsis-induced circulatory collapse, thus improving septic outcomes in mice. Biomed Pharmacother 2024; 178:117191. [PMID: 39079263 DOI: 10.1016/j.biopha.2024.117191] [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: 05/27/2024] [Revised: 07/12/2024] [Accepted: 07/22/2024] [Indexed: 08/25/2024] Open
Abstract
Casein kinase II (CK2) has recently emerged as a pivotal mediator in the propagation of inflammation across various diseases. Nevertheless, its role in the pathogenesis of sepsis remains unexplored. Here, we investigated the involvement of CK2 in sepsis progression and the potential beneficial effects of silmitasertib, a selective and potent CK2α inhibitor, currently under clinical trials for COVID-19 and cancer. Sepsis was induced by caecal ligation and puncture (CLP) in four-month-old C57BL/6OlaHsd mice. One hour after the CLP/Sham procedure, animals were assigned to receive silmitasertib (50 mg/kg/i.v.) or vehicle. Plasma/organs were collected at 24 h for analysis. A second set of experiments was performed for survival rate over 120 h. Septic mice developed multiorgan failure, including renal dysfunction due to hypoperfusion (reduced renal blood flow) and increased plasma levels of creatinine. Renal derangements were associated with local overactivation of CK2, and downstream activation of the NF-ĸB-iNOS-NO axis, paralleled by a systemic cytokine storm. Interestingly, all markers of injury/inflammation were mitigated following silmitasertib administration. Additionally, when compared to sham-operated mice, sepsis led to vascular hyporesponsiveness due to an aberrant systemic and local release of NO. Silmitasertib restored sepsis-induced vascular abnormalities. Overall, these pharmacological effects of silmitasertib significantly reduced sepsis mortality. Our findings reveal, for the first time, the potential benefits of a selective and potent CK2 inhibitor to counteract sepsis-induced hyperinflammatory storm, vasoplegia, and ultimately prolonging the survival of septic mice, thus suggesting a pivotal role of CK2 in sepsis and silmitasertib as a novel powerful pharmacological tool for drug repurposing in sepsis.
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Affiliation(s)
- Gustavo Ferreira Alves
- Department of Neurosciences (Rita Levi Montalcini), University of Turin, Turin, Italy; Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, Brazil; Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy
| | - Eleonora Aimaretti
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | | | - Giacomo Einaudi
- Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy
| | - Elisa Porchietto
- Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy
| | - Chiara Rubeo
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | - Enrica Marzani
- Department of Neurosciences (Rita Levi Montalcini), University of Turin, Turin, Italy
| | - Manuela Aragno
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | | | - Carlo Cifani
- Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy
| | - Daniel Fernandes
- Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, Brazil
| | - Massimo Collino
- Department of Neurosciences (Rita Levi Montalcini), University of Turin, Turin, Italy.
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10
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De Backer D, Khanna AK. The Ideal Mean Arterial Pressure Target Debate: Heterogeneity Obscures Conclusions. Crit Care Med 2024; 52:1495-1498. [PMID: 39145710 DOI: 10.1097/ccm.0000000000006331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/16/2024]
Affiliation(s)
- Daniel De Backer
- Department of Intensive Care, CHIREC Hospitals, Université Libre de Bruxelles, Brussels, Belgium
| | - Ashish K Khanna
- Department of Anesthesiology, Section on Critical Care Medicine, Wake Forest School of Medicine, Wake Forest University Health Sciences, Winston-Salem, NC
- Outcomes Research Consortium, Cleveland, OH
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11
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L'Écuyer S, Charbonney E, Carrier FM, Rose CF. Implication of Hypotension in the Pathogenesis of Cognitive Impairment and Brain Injury in Chronic Liver Disease. Neurochem Res 2024; 49:1437-1449. [PMID: 36635437 DOI: 10.1007/s11064-022-03854-z] [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: 07/25/2022] [Revised: 09/23/2022] [Accepted: 12/26/2022] [Indexed: 01/14/2023]
Abstract
The incidence of chronic liver disease is on the rise. One of the primary causes of hospital admissions for patients with cirrhosis is hepatic encephalopathy (HE), a debilitating neurological complication. HE is defined as a reversible syndrome, yet there is growing evidence stating that, under certain conditions, HE is associated with permanent neuronal injury and irreversibility. The pathophysiology of HE primarily implicates a strong role for hyperammonemia, but it is believed other pathogenic factors are involved. The fibrotic scarring of the liver during the progression of chronic liver disease (cirrhosis) consequently leads to increased hepatic resistance and circulatory anomalies characterized by portal hypertension, hyperdynamic circulatory state and systemic hypotension. The possible repercussions of these circulatory anomalies on brain perfusion, including impaired cerebral blood flow (CBF) autoregulation, could be implicated in the development of HE and/or permanent brain injury. Furthermore, hypotensive insults incurring during gastrointestinal bleed, infection, or liver transplantation may also trigger or exacerbate brain dysfunction and cell damage. This review will focus on the role of hypotension in the onset of HE as well as in the occurrence of neuronal cell loss in cirrhosis.
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Affiliation(s)
- Sydnée L'Écuyer
- Hepato-Neuro Laboratory, Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), 900, rue Saint-Denis - Pavillon R, R08.422 Montréal (Québec), Québec, H2X 0A9, Canada
| | - Emmanuel Charbonney
- Department of Medicine, Critical Care Division, Centre Hospitalier de l'Université de Montréal, Montréal, Canada
| | - François Martin Carrier
- Department of Medicine, Critical Care Division, Centre Hospitalier de l'Université de Montréal, Montréal, Canada
- Department of Anesthesiology, Centre Hospitalier de l'Université de Montréal, Montréal, Canada
- Carrefour de l'innovation et santé des populations , Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Canada
| | - Christopher F Rose
- Hepato-Neuro Laboratory, Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), 900, rue Saint-Denis - Pavillon R, R08.422 Montréal (Québec), Québec, H2X 0A9, Canada.
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12
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Hernández G, Valenzuela ED, Kattan E, Castro R, Guzmán C, Kraemer AE, Sarzosa N, Alegría L, Contreras R, Oviedo V, Bravo S, Soto D, Sáez C, Ait-Oufella H, Ospina-Tascón G, Bakker J. Capillary refill time response to a fluid challenge or a vasopressor test: an observational, proof-of-concept study. Ann Intensive Care 2024; 14:49. [PMID: 38558268 PMCID: PMC10984906 DOI: 10.1186/s13613-024-01275-5] [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: 01/03/2024] [Accepted: 03/10/2024] [Indexed: 04/04/2024] Open
Abstract
BACKGROUND Several studies have validated capillary refill time (CRT) as a marker of tissue hypoperfusion, and recent guidelines recommend CRT monitoring during septic shock resuscitation. Therefore, it is relevant to further explore its kinetics of response to short-term hemodynamic interventions with fluids or vasopressors. A couple of previous studies explored the impact of a fluid bolus on CRT, but little is known about the impact of norepinephrine on CRT when aiming at a higher mean arterial pressure (MAP) target in septic shock. We designed this observational study to further evaluate the effect of a fluid challenge (FC) and a vasopressor test (VPT) on CRT in septic shock patients with abnormal CRT after initial resuscitation. Our purpose was to determine the effects of a FC in fluid-responsive patients, and of a VPT aimed at a higher MAP target in chronically hypertensive fluid-unresponsive patients on the direction and magnitude of CRT response. METHODS Thirty-four septic shock patients were included. Fluid responsiveness was assessed at baseline, and a FC (500 ml/30 mins) was administered in 9 fluid-responsive patients. A VPT was performed in 25 patients by increasing norepinephrine dose to reach a MAP to 80-85 mmHg for 30 min. Patients shared a multimodal perfusion and hemodynamic monitoring protocol with assessments at at least two time-points (baseline, and at the end of interventions). RESULTS CRT decreased significantly with both tests (from 5 [3.5-7.6] to 4 [2.4-5.1] sec, p = 0.008 after the FC; and from 4.0 [3.3-5.6] to 3 [2.6 -5] sec, p = 0.03 after the VPT. A CRT-response was observed in 7/9 patients after the FC, and in 14/25 pts after the VPT, but CRT deteriorated in 4 patients on this latter group, all of them receiving a concomitant low-dose vasopressin. CONCLUSIONS Our findings support that fluid boluses may improve CRT or produce neutral effects in fluid-responsive septic shock patients with persistent hypoperfusion. Conversely, raising NE doses to target a higher MAP in previously hypertensive patients elicits a more heterogeneous response, improving CRT in the majority, but deteriorating skin perfusion in some patients, a fact that deserves further research.
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Affiliation(s)
- Glenn Hernández
- Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Avenida Diagonal Paraguay 362, Santiago, Chile.
| | - Emilio Daniel Valenzuela
- Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Avenida Diagonal Paraguay 362, Santiago, Chile
| | - Eduardo Kattan
- Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Avenida Diagonal Paraguay 362, Santiago, Chile
| | - Ricardo Castro
- Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Avenida Diagonal Paraguay 362, Santiago, Chile
| | - Camila Guzmán
- Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Avenida Diagonal Paraguay 362, Santiago, Chile
| | - Alicia Elzo Kraemer
- Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Avenida Diagonal Paraguay 362, Santiago, Chile
| | - Nicolás Sarzosa
- Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Avenida Diagonal Paraguay 362, Santiago, Chile
| | - Leyla Alegría
- Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Avenida Diagonal Paraguay 362, Santiago, Chile
| | - Roberto Contreras
- Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Avenida Diagonal Paraguay 362, Santiago, Chile
| | - Vanessa Oviedo
- Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Avenida Diagonal Paraguay 362, Santiago, Chile
| | - Sebastián Bravo
- Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Avenida Diagonal Paraguay 362, Santiago, Chile
| | - Dagoberto Soto
- Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Avenida Diagonal Paraguay 362, Santiago, Chile
| | - Claudia Sáez
- Departamento de Hematología Oncología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Hafid Ait-Oufella
- Medical Intensive Care Unit, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Paris, France
| | - Gustavo Ospina-Tascón
- Cardiovascular Research Center, INSERM U970, Université de Paris, Paris, France
- Department of Intensive Care Medicine, Fundación Valle del Lili, Cali, Colombia
- Translational Research Laboratory in Critical Care Medicine (TransLab-CCM), Universidad Icesi, Cali, Colombia
| | - Jan Bakker
- Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Avenida Diagonal Paraguay 362, Santiago, Chile
- Department of Intensive Care Adults, Erasmus MC University Medical Center, Rotterdam, Netherlands
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13
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Yao Z, Chen Y, Li D, Li Y, Liu Y, Fan H. HEMORRHAGIC SHOCK ASSESSED BY TISSUE MICROCIRCULATORY MONITORING: A NARRATIVE REVIEW. Shock 2024; 61:509-519. [PMID: 37878487 DOI: 10.1097/shk.0000000000002242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2023]
Abstract
ABSTRACT Hemorrhagic shock (HS) is a common complication after traumatic injury. Early identification of HS can reduce patients' risk of death. Currently, the identification of HS relies on macrocirculation indicators such as systolic blood pressure and heart rate, which are easily affected by the body's compensatory functions. Recently, the independence of the body's overall macrocirculation from microcirculation has been demonstrated, and microcirculation indicators have been widely used in the evaluation of HS. In this study, we reviewed the progress of research in the literature on the use of microcirculation metrics to monitor shock. We analyzed the strengths and weaknesses of each metric and found that microcirculation monitoring could not only indicate changes in tissue perfusion before changes in macrocirculation occurred but also correct tissue perfusion and cell oxygenation after the macrocirculation index returned to normal following fluid resuscitation, which is conducive to the early prediction and prognosis of HS. However, microcirculation monitoring is greatly affected by individual differences and environmental factors. Therefore, the current limitations of microcirculation assessments mean that they should be incorporated as part of an overall assessment of HS patients. Future research should explore how to better combine microcirculation and macrocirculation monitoring for the early identification and prognosis of HS patients.
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Affiliation(s)
| | | | | | - Yongnan Li
- Department of Cardiac Surgery, Lanzhou University Second Hospital, Lanzhou, China
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14
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Heybe MA, Mehta KJ. Role of albumin infusion in cirrhosis-associated complications. Clin Exp Med 2024; 24:58. [PMID: 38551716 PMCID: PMC10980629 DOI: 10.1007/s10238-024-01315-1] [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: 01/26/2024] [Accepted: 02/29/2024] [Indexed: 04/01/2024]
Abstract
Cirrhosis is an advanced-stage liver disease that occurs due to persistent physiological insults such as excessive alcohol consumption, infections, or toxicity. It is characterised by scar tissue formation, portal hypertension, and ascites (accumulation of fluid in the abdominal cavity) in decompensated cirrhosis. This review evaluates how albumin infusion ameliorates cirrhosis-associated complications. Since albumin is an oncotic plasma protein, albumin infusion allows movement of water into the intravascular space, aids with fluid resuscitation, and thereby contributes to resolving cirrhosis-induced hypovolemia (loss of extracellular fluid) seen in ascites. Thus, albumin infusion helps prevent paracentesis-induced circulatory dysfunction, a complication that occurs when treating ascites. When cirrhosis advances, other complications such as spontaneous bacterial peritonitis and hepatorenal syndrome can manifest. Infused albumin helps mitigate these by exhibiting plasma expansion, antioxidant, and anti-inflammatory functions. In hepatic encephalopathy, albumin infusion is thought to improve cognitive function by reducing ammonia concentration in blood and thereby tackle cirrhosis-induced hepatocyte malfunction in ammonia clearance. Infused albumin can also exhibit protective effects by binding to the cirrhosis-induced proinflammatory cytokines TNFα and IL6. While albumin administration has shown to prolong overall survival of cirrhotic patients with ascites in the ANSWER trial, the ATTIRE and MACHT trials have shown either no effect or limitations such as development of pulmonary oedema and multiorgan failure. Thus, albumin infusion is not a generic treatment option for all cirrhosis patients. Interestingly, cirrhosis-induced structural alterations in native albumin (which lead to formation of different albumin isoforms) can be used as prognostic biomarkers because specific albumin isoforms indicate certain complications of decompensated cirrhosis.
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Affiliation(s)
- Mohamed A Heybe
- GKT School of Medical Education, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Kosha J Mehta
- Centre for Education, Faculty of Life Sciences and Medicine, King's College London, London, UK.
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15
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Ye E, Ye H, Wang S, Fang X. INITIATION TIMING OF VASOPRESSOR IN PATIENTS WITH SEPTIC SHOCK: A SYSTEMATIC REVIEW AND META-ANALYSIS. Shock 2023; 60:627-636. [PMID: 37695641 DOI: 10.1097/shk.0000000000002214] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/12/2023]
Abstract
ABSTRACT Background: Vasopressor plays a crucial role in septic shock. However, the time for vasopressor initiation remains controversial. We conducted a systematic review and meta-analysis to explore its initiation timing for septic shock patients. Methods: PubMed, Cochrane Library, Embase, and Web of Sciences were searched from inception to July 12, 2023, for relevant studies. Primary outcome was short-term mortality. Meta-analysis was performed using Stata 15.0. Results: Twenty-three studies were assessed, including 2 randomized controlled trials and 21 cohort studies. The early group resulted in lower short-term mortality than the late group (OR [95% CI] = 0.775 [0.673 to 0.893], P = 0.000, I2 = 67.8%). The significance existed in the norepinephrine and vasopressin in subgroup analysis. No significant difference was considered in the association between each hour's vasopressor delay and mortality (OR [95% CI] = 1.02 [0.99 to 1.051], P = 0.195, I2 = 57.5%). The early group had an earlier achievement of target MAP ( P < 0.001), shorter vasopressor use duration ( P < 0.001), lower serum lactate level at 24 h ( P = 0.003), lower incidence of kidney injury ( P = 0.001), renal replacement therapy use ( P = 0.022), and longer ventilation-free days to 28 days ( P < 0.001). Conclusions: Early initiation of vasopressor (1-6 h within septic shock onset) would be more beneficial to septic shock patients. The conclusion needs to be further validated by more well-designed randomized controlled trials.
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Affiliation(s)
- Enci Ye
- Department of Anesthesiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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16
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Zhou HX, Yang CF, Wang HY, Teng Y, He HY. Should we initiate vasopressors earlier in patients with septic shock: A mini systemic review. World J Crit Care Med 2023; 12:204-216. [PMID: 37745258 PMCID: PMC10515096 DOI: 10.5492/wjccm.v12.i4.204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 06/28/2023] [Accepted: 07/17/2023] [Indexed: 09/05/2023] Open
Abstract
Septic shock treatment remains a major challenge for intensive care units, despite the recent prominent advances in both management and outcomes. Vasopressors serve as a cornerstone of septic shock therapy, but there is still controversy over the timing of administration. Specifically, it remains unclear whether vasopressors should be used early in the course of treatment. Here, we provide a systematic review of the literature on the timing of vasopressor administration. Research was systematically identified through PubMed, Embase and Cochrane searching according to PRISMA guidelines. Fourteen studies met the eligibility criteria and were included in the review. The pathophysiological basis for early vasopressor use was classified, with the exploration on indications for the early administration of mono-vasopressors or their combination with vasopressin or angiotensinII. We found that mortality was 28.1%-47.7% in the early vasopressors group, and 33.6%-54.5% in the control group. We also investigated the issue of vasopressor responsiveness. Furthermore, we acknowledged the subsequent challenge of administration of high-dose norepinephrine via peripheral veins with early vasopressor use. Based on the literature review, we propose a possible protocol for the early initiation of vasopressors in septic shock resuscitation.
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Affiliation(s)
- Hang-Xiang Zhou
- Department of Critical Care Medicine, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou Province, China
- Department of Critical Care Medicine, The Sixth Hospital of Guiyang, Guiyang 550002, Guizhou Province, China
| | - Chun-Fu Yang
- Department of Critical Care Medicine, The Sixth Hospital of Guiyang, Guiyang 550002, Guizhou Province, China
- Department of Respiratory Medicine, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550002, Guizhou Province, China
| | - He-Yan Wang
- Department of Critical Care Medicine, The Sixth Hospital of Guiyang, Guiyang 550002, Guizhou Province, China
- School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550002, Guizhou Province, China
| | - Yin Teng
- Department of Thoracic Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou Province, China
| | - Hang-Yong He
- Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Beijing 100020, China
- Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Beijing 100020, China
- Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Beijing Chao-Yang Hospital, Beijing 100020, China
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17
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Abstract
Cardiogenic shock is characterized by tissue hypoxia caused by circulatory failure arising from inadequate cardiac output. In addition to treating the pathologic process causing impaired cardiac function, prompt hemodynamic support is essential to reduce the risk of developing multiorgan dysfunction and to preserve cellular metabolism. Pharmacologic therapy with the use of vasopressors and inotropes is a key component of this treatment strategy, improving perfusion by increasing cardiac output, altering systemic vascular resistance, or both, while allowing time and hemodynamic stability to treat the underlying disease process implicated in the development of cardiogenic shock. Despite the use of mechanical circulatory support recently garnering significant interest, pharmacologic hemodynamic support remains a cornerstone of cardiogenic shock management, with over 90% of patients receiving at least 1 vasoactive agent. This review aims to describe the pharmacology and hemodynamic effects of current pharmacotherapies and provide a practical approach to their use, while highlighting important future research directions.
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Affiliation(s)
- Jason E. Bloom
- Department of CardiologyAlfred HealthMelbourneAustralia
- Baker Heart and Diabetes InstituteMelbourneAustralia
- Department of Epidemiology and Preventive MedicineMonash UniversityMelbourneAustralia
| | - William Chan
- Department of CardiologyAlfred HealthMelbourneAustralia
- Baker Heart and Diabetes InstituteMelbourneAustralia
| | - David M. Kaye
- Department of CardiologyAlfred HealthMelbourneAustralia
- Baker Heart and Diabetes InstituteMelbourneAustralia
| | - Dion Stub
- Department of CardiologyAlfred HealthMelbourneAustralia
- Department of Epidemiology and Preventive MedicineMonash UniversityMelbourneAustralia
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18
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Maiwall R, Rao Pasupuleti SS, Hidam AK, Kumar A, Tevethia HV, Vijayaraghavan R, Majumdar A, Prasher A, Thomas S, Mathur RP, Kumar G, Sarin SK. A randomised-controlled trial (TARGET-C) of high vs. low target mean arterial pressure in patients with cirrhosis and septic shock. J Hepatol 2023; 79:349-361. [PMID: 37088310 DOI: 10.1016/j.jhep.2023.04.006] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Revised: 03/17/2023] [Accepted: 04/04/2023] [Indexed: 04/25/2023]
Abstract
BACKGROUND & AIMS A high mean arterial pressure (MAP) target has been associated with improved renal outcomes in patients with cirrhosis, though it has not been studied in critically ill patients with cirrhosis and septic shock (CICs). We compared the efficacy of a high (80-85 mmHg; H-MAP) vs. low (60-65; L-MAP) target MAP strategy in improving 28-day mortality in CICs. METHODS We performed open-label 1:1 randomisation of 150 CICs (H-MAP 75; L-MAP 75). The primary endpoint was 28-day mortality and secondary endpoints included reversal of shock, acute kidney injury (AKI) at day 5, the incidence of intradialytic hypotension (IDH), and adverse events. Endothelial markers were analysed in a subset of patients. RESULTS The baseline characteristics were comparable. On intention-to-treat analysis, 28-day mortality (65% vs. 56%; p = 0.54), reversal of shock (47% vs. 53%; p = 0.41) and AKI development (45% vs. 31%;p = 0.06) were not different between the H-MAP and L-MAP groups, respectively. A lower incidence of IDH (12% vs. 48%; p <0.001) and higher adverse events necessitating protocol discontinuation (24% vs. 11%; p = 0.031) were noted in the H-MAP group. On per-protocol analysis (L-MAP 67; H-MAP 57), a significantly higher reversal of AKI (53% vs. 31%; p = 0.02) and a lower incidence of IDH (4% vs. 53%; p <0.001) were observed in the H-MAP group. Endothelial repair markers such as ADAMTS (2.11 ± 1.13 vs. 1.15 ± 0.48; p = 0.002) and angiopoietin-2 (74.08 ± 53.00 vs. 41.80 ± 15.95; p = 0.016) were higher in the H-MAP group. CONCLUSIONS A higher MAP strategy does not confer a survival benefit in CICs, but improves tolerance to dialysis, lactate clearance and renal recovery. Higher adverse events indicate the need for better tools to evaluate target microcirculation pressures in CICs. IMPACT AND IMPLICATIONS Maintaining an appropriate organ perfusion pressure during sepsis is the ultimate goal of haemodynamic management. A higher mean arterial pressure (MAP) improves renal outcomes in patients with hepatorenal syndrome. Patients with cirrhosis and septic shock have severe circulatory disturbances, low MAP, and poor tissue perfusion. In these patients, targeting higher MAP vs. lower MAP does not confer any survival benefit but is associated with more adverse events. A higher target strategy was associated with better tolerance and lesser episodes of hypotension on dialysis. Patients who could achieve the higher target MAP, without the development of adverse events, had improved renal outcomes and better lactate clearance. Higher MAP was also associated with improvements in markers of endothelial function. A higher target MAP strategy, with close monitoring of adverse events, may be recommended for patients with cirrhosis and septic shock. CLINICAL TRIAL NUMBER NCT03145168.
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Affiliation(s)
- Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Samba Siva Rao Pasupuleti
- Department of Statistics, Mizoram University (A Central University), Pachhunga University College Campus, Aizawl, India; Department of Applied Mathematics and Statistics, Mizoram University (A Central University), Pachhunga University College Campus, Aizawl, India
| | - Ashini Kumar Hidam
- Department of Clinical and Molecular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Anupam Kumar
- Department of Clinical and Molecular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Rajan Vijayaraghavan
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Arpita Majumdar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Adarsh Prasher
- Department of Clinical and Molecular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Sherin Thomas
- Department of Biochemistry, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Guresh Kumar
- Department of Statistics, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
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19
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Ospina-Tascón GA, Aldana JL, García Marín AF, Calderón-Tapia LE, Marulanda A, Escobar EP, García-Gallardo G, Orozco N, Velasco MI, Ríos E, De Backer D, Hernández G, Bakker J. Immediate Norepinephrine in Endotoxic Shock: Effects on Regional and Microcirculatory Flow. Crit Care Med 2023; 51:e157-e168. [PMID: 37255347 DOI: 10.1097/ccm.0000000000005885] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
OBJECTIVES To investigate the effects of immediate start of norepinephrine versus initial fluid loading followed by norepinephrine on macro hemodynamics, regional splanchnic and intestinal microcirculatory flows in endotoxic shock. DESIGN Animal experimental study. SETTING University translational research laboratory. SUBJECTS Fifteen Landrace pigs. INTERVENTIONS Shock was induced by escalating dose of lipopolysaccharide. Animals were allocated to immediate start of norepinephrine (i-NE) ( n = 6) versus mandatory 1-hour fluid loading (30 mL/kg) followed by norepinephrine (i-FL) ( n = 6). Once mean arterial pressure greater than or equal to 75 mm Hg was, respectively, achieved, successive mini-fluid boluses of 4 mL/kg of Ringer Lactate were given whenever: a) arterial lactate greater than 2.0 mmol/L or decrease less than 10% per 30 min and b) fluid responsiveness was judged to be positive. Three additional animals were used as controls (Sham) ( n = 3). Time × group interactions were evaluated by repeated-measures analysis of variance. MEASUREMENTS AND MAIN RESULTS Hypotension was significantly shorter in i-NE group (7.5 min [5.5-22.0 min] vs 49.3 min [29.5-60.0 min]; p < 0.001). Regional mesenteric and microcirculatory flows at jejunal mucosa and serosa were significantly higher in i-NE group at 4 and 6 hours after initiation of therapy ( p = 0.011, p = 0.032, and p = 0.017, respectively). Misdistribution of intestinal microcirculatory blood flow at the onset of shock was significantly reversed in i-NE group ( p < 0.001), which agreed with dynamic changes in mesenteric-lactate levels ( p = 0.01) and venous-to-arterial carbon dioxide differences ( p = 0.001). Animals allocated to i-NE showed significantly higher global end-diastolic volumes ( p = 0.015) and required significantly less resuscitation fluids ( p < 0.001) and lower doses of norepinephrine ( p = 0.001) at the end of the experiment. Pulmonary vascular permeability and extravascular lung water indexes were significantly lower in i-NE group ( p = 0.021 and p = 0.004, respectively). CONCLUSIONS In endotoxemic shock, immediate start of norepinephrine significantly improved regional splanchnic and intestinal microcirculatory flows when compared with mandatory fixed-dose fluid loading preceding norepinephrine. Immediate norepinephrine strategy was related with less resuscitation fluids and lower vasopressor doses at the end of the experiment.
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Affiliation(s)
- Gustavo A Ospina-Tascón
- Department of Intensive Care, Fundación Valle del Lili, Cali, Colombia
- Translational Research Laboratory in Critical Care Medicine (TransLab-CCM), Universidad Icesi, Cali, Colombia
| | - José L Aldana
- Department of Intensive Care, Fundación Valle del Lili, Cali, Colombia
- Translational Research Laboratory in Critical Care Medicine (TransLab-CCM), Universidad Icesi, Cali, Colombia
| | - Alberto F García Marín
- Department of Intensive Care, Fundación Valle del Lili, Cali, Colombia
- Translational Research Laboratory in Critical Care Medicine (TransLab-CCM), Universidad Icesi, Cali, Colombia
| | - Luis E Calderón-Tapia
- Department of Intensive Care, Fundación Valle del Lili, Cali, Colombia
- Translational Research Laboratory in Critical Care Medicine (TransLab-CCM), Universidad Icesi, Cali, Colombia
| | - Angela Marulanda
- Department of Intensive Care, Fundación Valle del Lili, Cali, Colombia
- Translational Research Laboratory in Critical Care Medicine (TransLab-CCM), Universidad Icesi, Cali, Colombia
| | - Elena P Escobar
- Department of Intensive Care, Fundación Valle del Lili, Cali, Colombia
- Translational Research Laboratory in Critical Care Medicine (TransLab-CCM), Universidad Icesi, Cali, Colombia
| | - Gustavo García-Gallardo
- Department of Intensive Care, Fundación Valle del Lili, Cali, Colombia
- Translational Research Laboratory in Critical Care Medicine (TransLab-CCM), Universidad Icesi, Cali, Colombia
| | - Nicolás Orozco
- Department of Intensive Care, Fundación Valle del Lili, Cali, Colombia
- Translational Research Laboratory in Critical Care Medicine (TransLab-CCM), Universidad Icesi, Cali, Colombia
| | - María I Velasco
- Department of Intensive Care, Fundación Valle del Lili, Cali, Colombia
- Translational Research Laboratory in Critical Care Medicine (TransLab-CCM), Universidad Icesi, Cali, Colombia
| | - Edwin Ríos
- Department of Intensive Care, Fundación Valle del Lili, Cali, Colombia
- Translational Research Laboratory in Critical Care Medicine (TransLab-CCM), Universidad Icesi, Cali, Colombia
| | - Daniel De Backer
- Intensive Care Department, CHIREC Hospitals, Université Libre de Bruxelles, Brussels, Belgium
| | - Glenn Hernández
- Departamento de Medicina Intensiva, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Jan Bakker
- Department of Intensive Care, Fundación Valle del Lili, Cali, Colombia
- Translational Research Laboratory in Critical Care Medicine (TransLab-CCM), Universidad Icesi, Cali, Colombia
- Intensive Care Department, CHIREC Hospitals, Université Libre de Bruxelles, Brussels, Belgium
- Departamento de Medicina Intensiva, Pontificia Universidad Católica de Chile, Santiago, Chile
- Department of Intensive Care Adults, Erasmus MC University Medical Center, Rotterdam, The Netherlands
- Department of Pulmonary and Critical Care, New York University, New York, NY
- Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Medical Center, New York, NY
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20
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Hamzaoui O, Goury A, Teboul JL. The Eight Unanswered and Answered Questions about the Use of Vasopressors in Septic Shock. J Clin Med 2023; 12:4589. [PMID: 37510705 PMCID: PMC10380663 DOI: 10.3390/jcm12144589] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 07/05/2023] [Accepted: 07/08/2023] [Indexed: 07/30/2023] Open
Abstract
Septic shock is mainly characterized-in addition to hypovolemia-by vasoplegia as a consequence of a release of inflammatory mediators. Systemic vasodilatation due to depressed vascular tone results in arterial hypotension, which induces or worsens organ hypoperfusion. Accordingly, vasopressor therapy is mandatory to correct hypotension and to reverse organ perfusion due to hypotension. Currently, two vasopressors are recommended to be used, norepinephrine and vasopressin. Norepinephrine, an α1-agonist agent, is the first-line vasopressor. Vasopressin is suggested to be added to norepinephrine in cases of inadequate mean arterial pressure instead of escalating the doses of norepinephrine. However, some questions about the bedside use of these vasopressors remain. Some of these questions have been well answered, some of them not clearly addressed, and some others not yet answered. Regarding norepinephrine, we firstly reviewed the arguments in favor of the choice of norepinephrine as a first-line vasopressor. Secondly, we detailed the arguments found in the recent literature in favor of an early introduction of norepinephrine. Thirdly, we reviewed the literature referring to the issue of titrating the doses of norepinephrine using an individualized resuscitation target, and finally, we addressed the issue of escalation of doses in case of refractory shock, a remaining unanswered question. For vasopressin, we reviewed the rationale for adding vasopressin to norepinephrine. Then, we discussed the optimal time for vasopressin administration. Subsequently, we addressed the issue of the optimal vasopressin dose, and finally we discussed the best strategy to wean these two vasopressors when combined.
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Affiliation(s)
- Olfa Hamzaoui
- Service de Médecine intensive réanimation polyvalente, Hôpital Robert Debré, CHU de Reims Université de Reims, 51092 Reims, France
- "Hémostase et Remodelage Vasculaire Post-Ischémie"-EA 3801, Unité HERVI, 51100 Reims, France
| | - Antoine Goury
- Service de Médecine intensive réanimation polyvalente, Hôpital Robert Debré, CHU de Reims Université de Reims, 51092 Reims, France
| | - Jean-Louis Teboul
- Service de médecine intensive-réanimation, Hôpital de Bicêtre, AP-HP, Université Paris-Saclay, DMU CORREVE, FHU SEPSIS, 94270 Le Kremlin-Bicêtre, France
- INSERM-UMR_S999 LabEx-LERMIT, Hôpital Marie-Lannelongue, 92350 Le Plessis Robinson, France
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21
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Wang CH, Fay K, Shashaty MG, Negoianu D. Volume Management with Kidney Replacement Therapy in the Critically Ill Patient. Clin J Am Soc Nephrol 2023; 18:788-802. [PMID: 37016472 PMCID: PMC10278821 DOI: 10.2215/cjn.0000000000000164] [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] [Received: 03/26/2023] [Accepted: 03/26/2023] [Indexed: 04/06/2023]
Abstract
While the administration of intravenous fluids remains an important treatment, the negative consequences of subsequent fluid overload have raised questions about when and how clinicians should pursue avenues of fluid removal. Decisions regarding fluid removal during critical illness are complex even for patients with preserved kidney function. This article seeks to apply general concepts of fluid management to the care of patients who also require KRT. Because optimal fluid management for any specific patient is likely to change over the course of critical illness, conceptual models using phases of care have been developed. In this review, we will examine the implications of one such model on the use of ultrafiltration during KRT for volume removal in distributive shock. This will also provide a useful lens to re-examine published data of KRT during critical illness. We will highlight recent prospective trials of KRT as well as recent retrospective studies examining ultrafiltration rate and mortality, review the results, and discuss applications and shortcomings of these studies. We also emphasize that current data and techniques suggest that optimal guidelines will not consist of recommendations for or against absolute fluid removal rates but will instead require the development of dynamic protocols involving frequent cycles of reassessment and adjustment of net fluid removal goals. If optimal fluid management is dynamic, then frequent assessment of fluid responsiveness, fluid toxicity, and tolerance of fluid removal will be needed. Innovations in our ability to assess these parameters may improve our management of ultrafiltration in the future.
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Affiliation(s)
- Christina H. Wang
- Renal, Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Kevin Fay
- Renal, Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
- Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Michael G.S. Shashaty
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
- Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Dan Negoianu
- Renal, Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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22
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Bruno RR, Wollborn J, Fengler K, Flick M, Wunder C, Allgäuer S, Thiele H, Schemmelmann M, Hornemann J, Moecke HME, Demirtas F, Palici L, Franz M, Saugel B, Kattan E, De Backer D, Bakker J, Hernandez G, Kelm M, Jung C. Direct assessment of microcirculation in shock: a randomized-controlled multicenter study. Intensive Care Med 2023; 49:645-655. [PMID: 37278760 PMCID: PMC10242221 DOI: 10.1007/s00134-023-07098-5] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 05/08/2023] [Indexed: 06/07/2023]
Abstract
PURPOSE Shock is a life-threatening condition characterized by substantial alterations in the microcirculation. This study tests the hypothesis that considering sublingual microcirculatory perfusion variables in the therapeutic management reduces 30-day mortality in patients admitted to the intensive care unit (ICU) with shock. METHODS This randomized, prospective clinical multicenter trial-recruited patients with an arterial lactate value above two mmol/L, requiring vasopressors despite adequate fluid resuscitation, regardless of the cause of shock. All patients received sequential sublingual measurements using a sidestream-dark field (SDF) video microscope at admission to the intensive care unit (± 4 h) and 24 (± 4) hours later that was performed blindly to the treatment team. Patients were randomized to usual routine or to integrating sublingual microcirculatory perfusion variables in the therapy plan. The primary endpoint was 30-day mortality, secondary endpoints were length of stay on the ICU and the hospital, and 6-months mortality. RESULTS Overall, we included 141 patients with cardiogenic (n = 77), post cardiac surgery (n = 27), or septic shock (n = 22). 69 patients were randomized to the intervention and 72 to routine care. No serious adverse events (SAEs) occurred. In the interventional group, significantly more patients received an adjustment (increase or decrease) in vasoactive drugs or fluids (66.7% vs. 41.8%, p = 0.009) within the next hour. Microcirculatory values 24 h after admission and 30-day mortality did not differ [crude: 32 (47.1%) patients versus 25 (34.7%), relative risk (RR) 1.39 (0.91-1.97); Cox-regression: hazard ratio (HR) 1.54 (95% confidence interval (CI) 0.90-2.66, p = 0.118)]. CONCLUSION Integrating sublingual microcirculatory perfusion variables in the therapy plan resulted in treatment changes that do not improve survival at all.
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Affiliation(s)
- Raphael Romano Bruno
- Medical Faculty, Department of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Duesseldorf, Moorenstraße 5, 40225, Duesseldorf, Germany
| | - Jakob Wollborn
- Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | - Karl Fengler
- Department of Cardiology, Heart Center Leipzig at University of Leipzig, Leipzig, Germany
| | - Moritz Flick
- Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christian Wunder
- Department of Anesthesiology and Intensive Care Medicine, Robert-Bosch-Krankenhaus, Stuttgart, Germany
| | | | - Holger Thiele
- Department of Cardiology, Heart Center Leipzig at University of Leipzig, Leipzig, Germany
| | - Mara Schemmelmann
- Medical Faculty, Department of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Duesseldorf, Moorenstraße 5, 40225, Duesseldorf, Germany
| | - Johanna Hornemann
- Medical Faculty, Department of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Duesseldorf, Moorenstraße 5, 40225, Duesseldorf, Germany
| | - Helene Mathilde Emilie Moecke
- Medical Faculty, Department of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Duesseldorf, Moorenstraße 5, 40225, Duesseldorf, Germany
| | - Filiz Demirtas
- Medical Faculty, Department of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Duesseldorf, Moorenstraße 5, 40225, Duesseldorf, Germany
| | - Lina Palici
- Medical Faculty, Department of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Duesseldorf, Moorenstraße 5, 40225, Duesseldorf, Germany
| | - Marcus Franz
- Department of Internal Medicine I, University Hospital Jena, Jena, Germany
| | - Bernd Saugel
- Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Eduardo Kattan
- Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Daniel De Backer
- Department of Intensive Care, CHIREC Hospitals, Université Libre de Bruxelles, Brussels, Belgium
| | - Jan Bakker
- NYU Langone Health and Columbia University Irving Medical Center, New York, USA
- Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Glenn Hernandez
- Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Malte Kelm
- Medical Faculty, Department of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Duesseldorf, Moorenstraße 5, 40225, Duesseldorf, Germany
- CARID (Cardiovascular Research Institute Düsseldorf), Düsseldorf, Germany
| | - Christian Jung
- Medical Faculty, Department of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Duesseldorf, Moorenstraße 5, 40225, Duesseldorf, Germany.
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23
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Munroe ES, Hyzy RC, Semler MW, Shankar-Hari M, Young PJ, Zampieri FG, Prescott HC. Evolving Management Practices for Early Sepsis-induced Hypoperfusion: A Narrative Review. Am J Respir Crit Care Med 2023; 207:1283-1299. [PMID: 36812500 PMCID: PMC10595457 DOI: 10.1164/rccm.202209-1831ci] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 02/22/2023] [Indexed: 02/24/2023] Open
Abstract
Sepsis causes significant morbidity and mortality worldwide. Resuscitation is a cornerstone of management. This review covers five areas of evolving practice in the management of early sepsis-induced hypoperfusion: fluid resuscitation volume, timing of vasopressor initiation, resuscitation targets, route of vasopressor administration, and use of invasive blood pressure monitoring. For each topic, we review the seminal evidence, discuss the evolution of practice over time, and highlight questions for additional research. Intravenous fluids are a core component of early sepsis resuscitation. However, with growing concerns about the harms of fluid, practice is evolving toward smaller-volume resuscitation, which is often paired with earlier vasopressor initiation. Large trials of fluid-restrictive, vasopressor-early strategies are providing more information about the safety and potential benefit of these approaches. Lowering blood pressure targets is a means to prevent fluid overload and reduce exposure to vasopressors; mean arterial pressure targets of 60-65 mm Hg appear to be safe, at least in older patients. With the trend toward earlier vasopressor initiation, the need for central administration of vasopressors has been questioned, and peripheral vasopressor use is increasing, although it is not universally accepted. Similarly, although guidelines suggest the use of invasive blood pressure monitoring with arterial catheters in patients receiving vasopressors, blood pressure cuffs are less invasive and often sufficient. Overall, the management of early sepsis-induced hypoperfusion is evolving toward fluid-sparing and less-invasive strategies. However, many questions remain, and additional data are needed to further optimize our approach to resuscitation.
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Affiliation(s)
- Elizabeth S. Munroe
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan, Ann Arbor, Michigan
| | - Robert C. Hyzy
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan, Ann Arbor, Michigan
| | - Matthew W. Semler
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Manu Shankar-Hari
- Centre for Inflammation Research, The University of Edinburgh, Edinburgh, United Kingdom
- Department of Intensive Care Medicine, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
| | - Paul J. Young
- Medical Research Institute of New Zealand, Wellington, New Zealand
- Intensive Care Unit, Wellington Hospital, Wellington, New Zealand
- Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia
- Department of Critical Care, University of Melbourne, Melbourne, Australia
| | - Fernando G. Zampieri
- Hospital do Coração (HCor) Research Institute, São Paulo, Brazil
- Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada; and
| | - Hallie C. Prescott
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan, Ann Arbor, Michigan
- VA Center for Clinical Management Research, Ann Arbor, Michigan
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24
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De Backer D. Novelties in the evaluation of microcirculation in septic shock. JOURNAL OF INTENSIVE MEDICINE 2023; 3:124-130. [PMID: 37188120 PMCID: PMC10175708 DOI: 10.1016/j.jointm.2022.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 08/25/2022] [Accepted: 09/01/2022] [Indexed: 05/17/2023]
Abstract
Microvascular alterations were first described in critically ill patients about 20 years ago. These alterations are characterized by a decrease in vascular density and presence of non-perfused capillaries close to well-perfused vessels. In addition, heterogeneity in microvascular perfusion is a key finding in sepsis. In this narrative review, we report our actual understanding of microvascular alterations, their role in the development of organ dysfunction, and the implications for outcome. Herein, we discuss the state of the potential therapeutic interventions and the potential impact of novel therapies. We also discuss how recent technologic development may affect the evaluation of microvascular perfusion.
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25
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Hamade B, Bayram JD, Hsieh YH, Khishfe B, Al Jalbout N. Modified Shock Index as a Predictor of Admission and In-hospital Mortality in Emergency Departments; an Analysis of a US National Database. ARCHIVES OF ACADEMIC EMERGENCY MEDICINE 2023; 11:e34. [PMID: 37215239 PMCID: PMC10197905 DOI: 10.22037/aaem.v11i1.1901] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
Introduction The modified shock index (MSI) is the ratio of heart rate to mean arterial pressure. It is used as a predictive and prognostic marker in a variety of disease states. This study aimed to derive the optimal MSI cut-off that is associated with increased likelihood (likelihood ratio, LR) of admission and in-hospital mortality in patients presenting to emergency department (ED). Methods We retrospectively reviewed data from the National Hospital Ambulatory Medical Care Survey between 2005 and 2010. Adults>18 years of age were included regardless of chief complaint. Basic patient demographics, initial vital signs, and outcomes were recorded for each patient. Then the optimal MSI cut-off for prediction of admission and in-hospital mortality in ED was calculated. LR ≥ 5 was considered clinically significant. Results 567,994,402 distinct weighted adult ED patient visits were included in the analysis. 15.7% and 2.4% resulted in admissions and in-hospital mortality, respectively. MSI > 1.7 was associated with a moderate increase in the likelihood of both admission (Positive LR (+LR) = 6.29) and in-hospital mortality (+LR = 5.12). +LR for hospital admission at MSI >1.7 was higher for men (7.13; 95% CI 7.11-7.15) compared to women (5.49; 95% CI 5.47-5.50) and for non-white (7.92; 95% CI 7.88-7.95) compared to white patients (5.85; 95% CI 5.84-5.86). For MSI <0.7, the +LRs were not clinically significant for admission (+LR = 1.07) or in-hospital mortality (LR = 0.75). Conclusion In this largest retrospective study, to date, on MSI in the undifferentiated ED population, we demonstrated that an MSI >1.7 on presentation is predictive of admission and in-hospital mortality. The use of MSI could help guide accurate acuity designation, resource allocation, and disposition.
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Affiliation(s)
- Bachar Hamade
- Center for Emergency Medicine, Main Campus and Department of Intensive Care and Resuscitation, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Jamil D. Bayram
- Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Yu-Hsiang Hsieh
- Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Basem Khishfe
- Department of Emergency Medicine, St. Elizabeth’s Hospital, O’Fallon, Illinois
| | - Nour Al Jalbout
- Department of Emergency Medicine, Massachusetts General Hospital, Boston, Massachusetts
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26
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Kido T, Okabe T, Narui S, Fujioka T, Ishigaki S, Usumoto S, Asukai Y, Kimura T, Shimazu S, Saito J, Oyama Y, Igawa W, Ono M, Ebara S, Yamamoto MH, Yakushiji T, Isomura N, Ochiai M. Relationship between early drop in systolic blood pressure, worsening renal function, and in-hospital mortality in patients with heart failure: a retrospective, observational study. Heart Vessels 2023; 38:207-215. [PMID: 36036287 DOI: 10.1007/s00380-022-02160-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 08/18/2022] [Indexed: 01/10/2023]
Abstract
This study aimed to determine the optimal cut-off value of the early drop in systolic blood pressure (SBP) for worsening renal function (WRF) in hospitalized patients with heart failure (HF) and analyze predictors of WRF and the early drop in SBP at that threshold. We retrospectively enrolled 396 patients with acute decompensated HF. The early drop in SBP was defined as the difference between baseline and SBP measured 24 h after hospitalization. We performed receiver operating characteristic (ROC) analysis to determine the optimal cut-off value of the early drop in SBP for WRF and evaluated the effect of the early drop in SBP on in-hospital mortality by multivariate logistic regression analyses. The mean age of the patients was 73.4 ± 14.7 years, and 61.2% were men. A 14.0% drop in SBP was identified as the optimal cut-off value for WRF from the ROC curve analysis. An early drop in SBP ≥ 14.0% was associated with WRF in multivariate logistic regression analysis (odds ratio 7.84; 95% confidence interval 4.06-15.14; P < 0.0001). The dose of intravenous furosemide within 24 h of admission was one of the predictors of the early drop in SBP ≥ 14.0%, while no early drop in SBP was a predictor of in-hospital mortality in multivariate logistic regression models. In conclusion, the optimal cut-off value for WRF in patients with HF was a 14.0% drop in SBP within 24 h of admission. The early drop in SBP ≥ 14.0% was one of the predictors of WRF in patients with HF. However, no early drop in SBP was associated with in-hospital mortality. This study was registered with the University Hospital Medical Information Network in Japan (UMIN000035989).
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Affiliation(s)
- Takehiko Kido
- Division of Cardiology, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-Chuo, Tsuzuki-ku, Yokohama, 224-8503, Japan
| | - Toshitaka Okabe
- Division of Cardiology, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-Chuo, Tsuzuki-ku, Yokohama, 224-8503, Japan.
| | - Shuro Narui
- Division of Cardiology, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-Chuo, Tsuzuki-ku, Yokohama, 224-8503, Japan
| | - Tatsuki Fujioka
- Division of Cardiology, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-Chuo, Tsuzuki-ku, Yokohama, 224-8503, Japan
| | - Shigehiro Ishigaki
- Division of Cardiology, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-Chuo, Tsuzuki-ku, Yokohama, 224-8503, Japan
| | - Soichiro Usumoto
- Division of Cardiology, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-Chuo, Tsuzuki-ku, Yokohama, 224-8503, Japan
| | - Yu Asukai
- Division of Cardiology, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-Chuo, Tsuzuki-ku, Yokohama, 224-8503, Japan
| | - Taro Kimura
- Division of Cardiology, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-Chuo, Tsuzuki-ku, Yokohama, 224-8503, Japan
| | - Suguru Shimazu
- Division of Cardiology, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-Chuo, Tsuzuki-ku, Yokohama, 224-8503, Japan
| | - Jumpei Saito
- Division of Cardiology, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-Chuo, Tsuzuki-ku, Yokohama, 224-8503, Japan
| | - Yuji Oyama
- Division of Cardiology, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-Chuo, Tsuzuki-ku, Yokohama, 224-8503, Japan
| | - Wataru Igawa
- Division of Cardiology, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-Chuo, Tsuzuki-ku, Yokohama, 224-8503, Japan
| | - Morio Ono
- Division of Cardiology, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-Chuo, Tsuzuki-ku, Yokohama, 224-8503, Japan
| | - Seitaro Ebara
- Division of Cardiology, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-Chuo, Tsuzuki-ku, Yokohama, 224-8503, Japan
| | - Myong Hwa Yamamoto
- Division of Cardiology, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-Chuo, Tsuzuki-ku, Yokohama, 224-8503, Japan
| | - Tadayuki Yakushiji
- Division of Cardiology, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-Chuo, Tsuzuki-ku, Yokohama, 224-8503, Japan
| | - Naoei Isomura
- Division of Cardiology, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-Chuo, Tsuzuki-ku, Yokohama, 224-8503, Japan
| | - Masahiko Ochiai
- Division of Cardiology, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-Chuo, Tsuzuki-ku, Yokohama, 224-8503, Japan
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Wang J, Weng L, Xu J, Du B. Blood gas analysis as a surrogate for microhemodynamic monitoring in sepsis. World J Emerg Med 2023; 14:421-427. [PMID: 37969221 PMCID: PMC10632753 DOI: 10.5847/wjem.j.1920-8642.2023.093] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Accepted: 05/14/2023] [Indexed: 11/17/2023] Open
Abstract
BACKGROUND Emergency patients with sepsis or septic shock are at high risk of death. Despite increasing attention to microhemodynamics, the clinical use of advanced microcirculatory assessment is limited due to its shortcomings. Since blood gas analysis is a widely used technique reflecting global oxygen supply and consumption, it may serve as a surrogate for microcirculation monitoring in septic treatment. METHODS We performed a search using PubMed, Web of Science, and Google scholar. The studies and reviews that were most relevant to septic microcirculatory dysfunctions and blood gas parameters were identified and included. RESULTS Based on the pathophysiology of oxygen metabolism, the included articles provided a general overview of employing blood gas analysis and its derived set of indicators for microhemodynamic monitoring in septic care. Notwithstanding flaws, several parameters are linked to changes in the microcirculation. A comprehensive interpretation of blood gas parameters can be used in order to achieve hemodynamic optimization in septic patients. CONCLUSION Blood gas analysis in combination with clinical performance is a reliable alternative for microcirculatory assessments. A deep understanding of oxygen metabolism in septic settings may help emergency physicians to better use blood gas analysis in the evaluation and treatment of sepsis and septic shock.
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Affiliation(s)
- Jingyi Wang
- Emergency Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
- Medical Intensive Care Unit, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Li Weng
- Medical Intensive Care Unit, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Jun Xu
- Emergency Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Bin Du
- Medical Intensive Care Unit, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
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Macdonald S, Peake SL, Corfield AR, Delaney A. Fluids or vasopressors for the initial resuscitation of septic shock. Front Med (Lausanne) 2022; 9:1069782. [PMID: 36507525 PMCID: PMC9729725 DOI: 10.3389/fmed.2022.1069782] [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: 10/14/2022] [Accepted: 11/07/2022] [Indexed: 11/25/2022] Open
Abstract
Intravenous fluid resuscitation is recommended first-line treatment for sepsis-associated hypotension and/or hypoperfusion. The rationale is to restore circulating volume and optimize cardiac output in the setting of shock. Nonetheless, there is limited high-level evidence to support this practice. Over the past decade emerging evidence of harm associated with large volume fluid resuscitation among patients with septic shock has led to calls for a more conservative approach. Specifically, clinical trials undertaken in Africa have found harm associated with initial fluid resuscitation in the setting of infection and hypoperfusion. While translating these findings to practice in other settings is problematic, there has been a re-appraisal of current practice with some recommending earlier use of vasopressors rather than repeated fluid boluses as an alternative to restore perfusion in septic shock. There is consequently uncertainty and variation in practice. The question of fluids or vasopressors for initial resuscitation in septic shock is the subject of international multicentre clinical trials.
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Affiliation(s)
- Stephen Macdonald
- Medical School, University of Western Australia, Perth, WA, Australia
- Department of Emergency Medicine, Royal Perth Hospital, Perth, WA, Australia
- Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, WA, Australia
| | - Sandra L. Peake
- Faculty of Health and Medical Sciences, School of Medicine, University of Adelaide, Adelaide, SA, Australia
- Department of Critical Care Research, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia
- Department of Intensive Care Medicine, The Queen Elizabeth Hospital, Adelaide, SA, Australia
| | - Alasdair R. Corfield
- Consultant Emergency Medicine, Royal Alexandra Hospital, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom
- School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, United Kingdom
| | - Anthony Delaney
- Malcolm Fisher Department of Intensive Care Medicine, Royal North Shore Hospital, Sydney, NSW, Australia
- Division of Critical Care, The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia
- Faculty of Medicine, Northern Clinical School, University of Sydney, Sydney, NSW, Australia
- Department of Epidemiology and Preventative Medicine, Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, VIC, Australia
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Murphy KM, Rishniw M, Silverstein DC. Use of vasopressors for treatment of vasodilatory hypotension in dogs and cats by Diplomates of the American College of Veterinary Emergency and Critical Care. J Vet Emerg Crit Care (San Antonio) 2022; 32:714-722. [PMID: 35829666 DOI: 10.1111/vec.13230] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 04/30/2021] [Accepted: 06/20/2021] [Indexed: 01/21/2023]
Abstract
OBJECTIVE To identify the most common practices of Diplomates of the American College of Veterinary Emergency and Critical Care (DACVECCs) as they relate to the recognition and treatment of hypotension in dogs and cats, particularly concerning the use of vasopressors in vasodilatory shock states. DESIGN A survey regarding vasopressor use was sent to all active DACVECCs using the Veterinary Information Network. Questions focused on respondent characteristics, method of recognition of hypotension, triggers for initiation of vasopressor therapy, first- and second-line vasopressor choice, and methods of determining response to therapy. SUBJECTS A total of 734 DACVECCs were invited to participate, and 203 Diplomates (27.7%) completed the survey. RESULTS For both dogs and cats, the most common first-line vasopressor was norepinephrine (87.9% in dogs and 83.1% in cats). The most common second-choice vasopressor was vasopressin (44.2% in dogs and 39.0% in cats). Cutoff values for initiating vasopressor therapy varied between species and modality used for blood pressure measurement. In general, most DACVECCs chose to initiate vasopressor therapy at a Doppler blood pressure <90 mm Hg or a mean arterial pressure of <60 or <65 mm Hg when using oscillometric or direct arterial blood pressure measurements in dogs and cats. CONCLUSIONS Most DACVECCs adhere to published human guidelines when choosing a first-line vasopressor. However, there is significant variability in blood pressure measurement technique, cutoffs for initiation of vasopressor use, and choice of second-line vasopressors.
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Affiliation(s)
- Kellyann M Murphy
- Department of Clinical Studies and Advanced Medicine, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA
| | - Mark Rishniw
- Veterinary Information Network, Davis, California, USA
| | - Deborah C Silverstein
- Department of Clinical Studies and Advanced Medicine, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA
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Rootjes PA, Chaara S, de Roij van Zuijdewijn CL, Nubé MJ, Wijngaarden G, Grooteman MP. High-Volume Hemodiafiltration and Cool Hemodialysis Have a Beneficial Effect on Intradialytic Hemodynamics: A Randomized Cross-Over Trial of Four Intermittent Dialysis Strategies. Kidney Int Rep 2022; 7:1980-1990. [PMID: 36090495 PMCID: PMC9459077 DOI: 10.1016/j.ekir.2022.06.021] [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: 06/13/2022] [Revised: 06/24/2022] [Accepted: 06/27/2022] [Indexed: 11/11/2022] Open
Abstract
Introduction Compared to standard hemodialysis (S-HD), postdilution hemodiafiltration (HDF) has been associated with improved survival. Methods To assess whether intradialytic hemodynamics may play a role in this respect, 40 chronic dialysis patients were cross-over randomized to S-HD (dialysate temperature [Td] 36.5 °C), cooled HD (C-HD; Td 35.5 °C), and HDF (low-volume [LV-HDF)] and high-volume [HV-HDF], both Td 36.5 °C, convection volume 15 liters, and at least 23 liters per session, respectively), each for 2 weeks. Blood pressure (BP) was measured every 15 minutes. The primary endpoint was the number of intradialytic hypotensive (IDH) episodes per session. IDH was defined as systolic BP (SBP) less than 90 mmHg for predialysis SBP less than 160 mmHg and less than 100 mmHg for predialysis SBP greater than or equal to 160 mmHg, independent of symptoms and interventions. A post hoc analysis on early-onset IDH was performed as well. Secondary endpoints included intradialytic courses of SBP, diastolic BP (DBP) and mean arterial pressure (MAP). Results During S-HD, IDH occurred 0.68 episodes per session, which was 3.2 and 2.5 times higher than during C-HD (0.21 per session, P < 0.0005) and HV-HDF (0.27 per session, P < 0.0005), respectively. Whereas the latter 2 strategies showed similar frequencies, HV-HDF differed significantly from LV-HDF (P = 0.02). A comparable trend was observed for early-onset IDH: S-HD (0.32 per session), C-HD (0.07 per session, P < 0.0005) and HV-HDF (0.10 per session, P = 0.001). SBP, DBP, and MAP declined during S-HD (−6.8, −5.2, −5.2 mmHg per session; P = 0.004, P < 0.0005, P = 0.002 respectively), which was markedly different from C-HD (P < 0.01). Conclusion Though C-HD and HV-HDF showed the lowest IDH frequency and the best intradialytic hemodynamic stability, all parameters were most disrupted in S-HD. Therefore, the survival benefit of HV-HDF over S-HD may be partly caused by a more beneficial intradialytic BP profile.
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Fage N, Demiselle J, Seegers V, Merdji H, Grelon F, Mégarbane B, Anguel N, Mira JP, Dequin PF, Gergaud S, Weiss N, Legay F, Le Tulzo Y, Conrad M, Coudroy R, Gonzalez F, Guitton C, Tamion F, Tonnelier JM, Bedos JP, Van Der Linden T, Vieillard-Baron A, Mariotte E, Pradel G, Lesieur O, Ricard JD, Hervé F, Du Cheyron D, Guerin C, Mercat A, Teboul JL, Radermacher P, Asfar P. Effects of mean arterial pressure target on mottling and arterial lactate normalization in patients with septic shock: a post hoc analysis of the SEPSISPAM randomized trial. Ann Intensive Care 2022; 12:78. [PMID: 35984574 PMCID: PMC9391564 DOI: 10.1186/s13613-022-01053-1] [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: 08/03/2022] [Accepted: 08/08/2022] [Indexed: 11/24/2022] Open
Abstract
Background In patients with septic shock, the impact of the mean arterial pressure (MAP) target on the course of mottling remains uncertain. In this post hoc analysis of the SEPSISPAM trial, we investigated whether a low-MAP (65 to 70 mmHg) or a high-MAP target (80 to 85 mmHg) would affect the course of mottling and arterial lactate in patients with septic shock. Methods The presence of mottling was assessed every 2 h from 2 h after inclusion to catecholamine weaning. We compared mottling and lactate time course between the two MAP target groups. We evaluated the patient’s outcome according to the presence or absence of mottling. Results We included 747 patients, 374 were assigned to the low-MAP group and 373 to the high-MAP group. There was no difference in mottling and lactate evolution during the first 24 h between the two MAP groups. After adjustment for MAP and confounding factors, the presence of mottling ≥ 6 h during the first 24 h was associated with a significantly higher risk of death at day 28 and 90. Patients without mottling or with mottling < 6 h and lactate ≥ 2 mmol/L have a higher probability of survival than those with mottling ≥ 6 h and lactate < 2 mmol/L. Conclusion Compared with low MAP target, higher MAP target did not alter mottling and lactate course. Mottling lasting for more than 6 h was associated with higher mortality. Compared to arterial lactate, mottling duration appears to be a better marker of mortality. Supplementary Information The online version contains supplementary material available at 10.1186/s13613-022-01053-1.
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Affiliation(s)
- Nicolas Fage
- Department of Medical Intensive Care, University Hospital of Angers, Angers, France.,MITOVASC Laboratory UMR INSERM (French National Institute of Health and Medical Research), 1083 - CNRS 6015, University of Angers, Angers, France
| | - Julien Demiselle
- Department of Intensive Care (Service de Médecine Intensive - Réanimation), Nouvel Hôpital Civil, University Hospital of Strasbourg, Strasbourg, France.,INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS (Fédération de Médecine Translationnelle de Strasbourg), University of Strasbourg, Strasbourg, France
| | - Valérie Seegers
- Service de Biométrie, Institut de Cancérologie de L'Ouest, Centre Paul Papin, Angers, France
| | - Hamid Merdji
- Department of Intensive Care (Service de Médecine Intensive - Réanimation), Nouvel Hôpital Civil, University Hospital of Strasbourg, Strasbourg, France.,INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS (Fédération de Médecine Translationnelle de Strasbourg), University of Strasbourg, Strasbourg, France
| | - Fabien Grelon
- Medical and Surgical Intensive Care Unit, Le Mans Hospital, Le Mans, France
| | - Bruno Mégarbane
- Department of Medical and Toxicological Critical Care, Lariboisière Hospital, Paris University, INSERM UMRS-1144, Paris, France
| | - Nadia Anguel
- Department of Medical Intensive Care, Bicêtre University Hospital, AP-HP, Paris-Saclay University, Le Kremlin Bicêtre, France
| | - Jean-Paul Mira
- Department of Medical Intensive Care, Cochin University Hospital, Paris, France
| | | | - Soizic Gergaud
- Department of Surgical Intensive Care, University Hospital of Angers, Angers, France
| | - Nicolas Weiss
- Department of Medical Intensive Care, Georges Pompidou European Hospital, Assistance Publique - Hôpitaux de Paris, University of Paris, Paris, France
| | - François Legay
- Medical and Surgical Intensive Care Unit, Saint Brieuc Hospital, Saint Brieuc, France
| | - Yves Le Tulzo
- Department of Infectious Diseases and Medical Intensive Care, Rennes University Hospital, Rennes, France
| | - Marie Conrad
- Department of Medical Intensive Care, Nancy University Hospital, Nancy, France
| | - Remi Coudroy
- Department of Medical Intensive Care, Université de Poitiers, CHU Poitiers, Poitiers, France
| | - Frédéric Gonzalez
- Department of Medical and Surgical Intensive Care, Avicenne Teaching Hospital, Bobigny, France
| | - Christophe Guitton
- Department of Medical Intensive Care, Nantes University Hospital, Nantes, France
| | - Fabienne Tamion
- Department of Medical Intensive Care, Rouen University Hospital, Rouen, France
| | | | | | - Thierry Van Der Linden
- Department of Intensive Care, Saint Philibert Hospital, Catholic University of Lille, Lille, France
| | - Antoine Vieillard-Baron
- Department of Medical Intensive Care, University Hospital of Ambroise Paré, Boulogne Billancourt, France.,Inserm U1018, Center for Research in Epidemiology and Population Health (CESP), Faculty of Paris Saclay, Villejuif, France
| | - Eric Mariotte
- Department of Intensive Care, Saint Louis Hospital, Paris, France
| | - Gaël Pradel
- Department of Intensive Care, Avignon Hospital, Avignon, France
| | - Olivier Lesieur
- Department of Medical and Surgical Intensive Care, La Rochelle Saint Louis Hospital, La Rochelle, France
| | - Jean-Damien Ricard
- Université de Paris, AP-HP, Hôpital Louis Mourier, DMU ESPRIT, Médecine Intensive Réanimation, Colombes, France
| | - Fabien Hervé
- Department of Medical and Surgical Intensive Care, Quimper Hospital, Quimper, France
| | - Damien Du Cheyron
- Department of Medical Intensive Care, Caen University Hospital, Caen, France
| | - Claude Guerin
- Department of Medical Intensive Care, Edouard Herriot Hospital, Lyon, France
| | - Alain Mercat
- Department of Medical Intensive Care, University Hospital of Angers, Angers, France
| | - Jean-Louis Teboul
- Department of Medical Intensive Care, Bicêtre University Hospital, AP-HP, Paris-Saclay University, Le Kremlin Bicêtre, France
| | - Peter Radermacher
- Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Helmholtzstrasse 8-1, Ulm, Germany
| | - Pierre Asfar
- Department of Medical Intensive Care, University Hospital of Angers, Angers, France.
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Mallat J, Rahman N, Hamed F, Hernandez G, Fischer MO. Pathophysiology, mechanisms, and managements of tissue hypoxia. Anaesth Crit Care Pain Med 2022; 41:101087. [PMID: 35462083 DOI: 10.1016/j.accpm.2022.101087] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 02/17/2022] [Accepted: 02/18/2022] [Indexed: 11/01/2022]
Abstract
Oxygen is needed to generate aerobic adenosine triphosphate and energy that is required to support vital cellular functions. Oxygen delivery (DO2) to the tissues is determined by convective and diffusive processes. The ability of the body to adjust oxygen extraction (ERO2) in response to changes in DO2 is crucial to maintain constant tissue oxygen consumption (VO2). The capability to increase ERO2 is the result of the regulation of the circulation and the effects of the simultaneous activation of both central and local factors. The endothelium plays a crucial role in matching tissue oxygen supply to demand in situations of acute drop in tissue oxygenation. Tissue oxygenation is adequate when tissue oxygen demand is met. When DO2 is severely compromised, a critical DO2 value is reached below which VO2 falls and becomes dependent on DO2, resulting in tissue hypoxia. The different mechanisms of tissue hypoxia are circulatory, anaemic, and hypoxic, characterised by a diminished DO2 but preserved capacity of increasing ERO2. Cytopathic hypoxia is another mechanism of tissue hypoxia that is due to impairment in mitochondrial respiration that can be observed in septic conditions with normal overall DO2. Sepsis induces microcirculatory alterations with decreased functional capillary density, increased number of stopped-flow capillaries, and marked heterogeneity between the areas with large intercapillary distance, resulting in impairment of the tissue to extract oxygen and to satisfy the increased tissue oxygen demand, leading to the development of tissue hypoxia. Different therapeutic approaches exist to increase DO2 and improve microcirculation, such as fluid therapy, transfusion, vasopressors, inotropes, and vasodilators. However, the effects of these agents on microcirculation are quite variable.
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Affiliation(s)
- Jihad Mallat
- Critical Care Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates; Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA; Normandy University, UNICAEN, ED 497, Caen, France.
| | - Nadeem Rahman
- Critical Care Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - Fadi Hamed
- Critical Care Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - Glenn Hernandez
- Departamento de Medicina Intensiva, Facultad de Medicina, Pontifcia Universidad Católica de Chile, Santiago, Chile
| | - Marc-Olivier Fischer
- Department of Anaesthesiology-Resuscitation and Perioperative Medicine, Normandy University, UNICAEN, Caen University Hospital, Normandy, Caen, France
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Near-Infrared Spectroscopy for Determination of Cardiac Output Augmentation in a Swine Model of Ischemia-Reperfusion Injury. Crit Care Explor 2022; 4:e0749. [PMID: 35982838 PMCID: PMC9380696 DOI: 10.1097/cce.0000000000000749] [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] [Indexed: 11/27/2022] Open
Abstract
CONTEXT: Near infrared spectroscopy (NIRS) is a noninvasive tool for assessing local oxygen balance. In circulatory shock, the microcirculatory environment as measured by NIRS during resuscitation may provide additional diagnostic tools of value to the critical care physician. HYPOTHESIS: To assess whether a relative increase in peripheral NIRS was correlated with a clinically relevant increase in cardiac output following a fluid bolus in a swine model of shock. METHODS AND MODELS: Nine healthy young adult swine with median weight 80 kg (interquartile range, 75–83 kg) were anesthetized and surgically instrumented. They underwent a controlled hemorrhage of 20% of their blood volume followed by partial or complete aortic occlusion to create a variable ischemia-reperfusion injury. Next, the animals underwent four 500-mL plasmalyte boluses over 9 minutes each followed by a 6-minute pause. The animal then underwent a 25% mixed auto/homologous blood transfusion followed by four more 500 mL plasmalyte boluses over 9 minutes. Finally, the animals underwent a 25% mixed auto/homologous blood transfusion followed by an additional four rounds of 500-mL plasmalyte boluses over 9 minutes. Left thoracic limb NIRS, descending thoracic aortic flow (dAF), arterial blood pressure (MAP), central venous pressure (CVP), and mixed central venous oxygen saturation (Svo2) were measured continuously for comparison. RESULTS: The area under the receiver operating curve for an increase in dAF of 10% in response to a 500 mL bolus based on a percent increase in the proximal NIRS was 0.82 with 95% CI, 0.72–0.91; Svo2, 0.86 with 95% CI, 0.78–0.95; MAP, 0.75 with 95% CI, 0.65–0.85 and CVP, 0.64 with 95% CI, 0.53–0.76. INTERPRETATION AND CONCLUSIONS: A dynamic relative increase in NIRS in response to a crystalloid challenge has moderate discriminatory power for cardiac output augmentation during shock in a swine model of ischemia-reperfusion injury. NIRS performed as well as invasive measurements (Svo2 and MAP) and better than CVP.
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Prehospital Bundle of Care Based on Antibiotic Therapy and Hemodynamic Optimization Is Associated With a 30-Day Mortality Decrease in Patients With Septic Shock. Crit Care Med 2022; 50:1440-1448. [PMID: 35904262 DOI: 10.1097/ccm.0000000000005625] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVES This study aims to investigate the association between the 30-day mortality in patients with septic shock (SS) and a prehospital bundle of care completion, antibiotic therapy administration, and hemodynamic optimization defined as a fluid expansion of at least 10 mL.kg-1.hr-1. DESIGN To assess the association between prehospital BUndle of Care (BUC) completion and 30-day mortality, the inverse probability treatment weighting (IPTW) propensity method was performed. SETTING International guidelines recommend early treatment implementation in order to reduce SS mortality. More than one single treatment, a bundle of care, including antibiotic therapy and hemodynamic optimization, is more efficient. PATIENTS From May 2016 to March 2021, patients with SS requiring prehospital mobile ICU (mICU) intervention were retrospectively analyzed. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Among the 529 patients with SS requiring action by the mICU enrolled in this study, 354 (67%) were analyzed. Presumed pulmonary, digestive, and urinary infections were the cause of the SS in 49%, 25%, and 13% of the cases, respectively. The overall 30-day mortality was 32%. Seventy-one patients (20%) received prehospital antibiotic therapy and fluid expansion. Log binomial regression weighted with IPTW resulted in a significant association between 30-day mortality and prehospital BUC completion (respiratory rate [RR] of 0.56 [0.33-0.89]; p = 0.02 and adjusted RR 0.52 [0.27-0.93]; p = 0.03). CONCLUSIONS A prehospital bundle of care, based on antibiotic therapy and hemodynamic optimization, is associated with a 30-day mortality decrease among patients suffering from SS cared for by an mICU.
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Krychtiuk KA, Vrints C, Wojta J, Huber K, Speidl WS. Basic mechanisms in cardiogenic shock: part 1-definition and pathophysiology. EUROPEAN HEART JOURNAL. ACUTE CARDIOVASCULAR CARE 2022; 11:356-365. [PMID: 35218350 DOI: 10.1093/ehjacc/zuac021] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 01/17/2022] [Accepted: 02/07/2022] [Indexed: 05/23/2023]
Abstract
Cardiogenic shock mortality rates remain high despite significant advances in cardiovascular medicine and the widespread uptake of mechanical circulatory support systems. Except for early invasive angiography and percutaneous coronary intervention of the infarct-related artery, the most widely used therapeutic measures are based on low-quality evidence. The grim prognosis and lack of high-quality data warrant further action. Part 1 of this two-part educational review defines cardiogenic shock and discusses current treatment strategies. In addition, we summarize current knowledge on basic mechanisms in the pathophysiology of cardiogenic shock, focusing on inflammation and microvascular disturbances, which may ultimately be translated into diagnostic or therapeutic approaches to improve the outcome of our patients.
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Affiliation(s)
- Konstantin A Krychtiuk
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria
- Duke Clinical Research Institute, Durham, NC, USA
| | - Christiaan Vrints
- Research Group Cardiovascular Diseases, Department GENCOR, University of Antwerp, Antwerp, Belgium
- Department of Cardiology, Antwerp University Hospital (UZA), Edegem, Belgium
| | - Johann Wojta
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria
- Ludwig Boltzmann Institute for Cardiovascular Research, Vienna, Austria
- Core Facilities, Medical University of Vienna, Vienna, Austria
| | - Kurt Huber
- Ludwig Boltzmann Institute for Cardiovascular Research, Vienna, Austria
- 3rd Department of Internal Medicine, Cardiology and Intensive Care Unit, Wilhelminenhospital, Vienna, Austria
- Medical School, Sigmund Freud University, Vienna, Austria
| | - Walter S Speidl
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria
- Ludwig Boltzmann Institute for Cardiovascular Research, Vienna, Austria
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Abstract
BACKGROUND/AIMS In patients with acute-on-chronic liver failure (ACLF), type 1 hepatorenal syndrome (HRS) is a critical organ failure complication that resulted in rapid mortality. There are no efficient parameters to predict HRS in hepatitis B virus (HBV)-related ACLF. To assess HBV-ACLF risk factors and evaluate the association between mean arterial pressures (MAP), HRS and survival in patients with HBV-ACLF. METHODS A total of 420 ACLF patients were screened from June 2015 to June 2016, and 57 HBV-ACLF patients were included in the study. Clinical data and MAP measurements of these patients were collected. Multivariate analyses, Cox proportional hazards regression and receiver operator characteristic (ROC) curves were used to analyze. RESULTS In a 30-day study period, 43 (75.44%) patients survived. Patients in the HRS group were older and had higher Model for End-Stage Liver Disease (MELD) scores than patients in the non-HRS group. A MAP drop of ≥9.5 mmHg was an independent predictor of HRS with a sensitivity and specificity of 92.86 and 69.77%, respectively. The baseline MELD score was also an independent risk factor of HRS. MAP drop (OR, 1.582; P = 0.000), prothrombin time, HRS, MELD and FIB were independent prognostic factors for 30-day mortality. The area under the ROC curve of MAP drop was 0.808 (P = 0.001). CONCLUSION A decrease in MAP was a valuable predictor of HRS in patients with HBV-related ACLF. MAP drop ≥9.5 mmHg may be useful for predicting patient prognosis and exploring new treatment measures in patients with HBV-related ACLF.
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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: 20] [Impact Index Per Article: 6.7] [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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Affiliation(s)
- Jean-Louis Vincent
- Department of Intensive Care, Erasme Hospital, Université libre de Bruxelles, Brussels, Belgium
| | - Alexandre Joosten
- Department of Anesthesiology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
- Department of Anesthesiology and Intensive Care, Hôpitaux Universitaires Paris-Sud, Université Paris-Sud, Université Paris-Saclay, Paul Brousse Hospital, Assistance Publique Hôpitaux de Paris (APHP), Villejuif, France
| | - Bernd Saugel
- Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Heterogeneous impact of hypotension on organ perfusion and outcomes: a narrative review. Br J Anaesth 2021; 127:845-861. [PMID: 34392972 DOI: 10.1016/j.bja.2021.06.048] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 06/08/2021] [Accepted: 06/25/2021] [Indexed: 12/20/2022] Open
Abstract
Arterial blood pressure is the driving force for organ perfusion. Although hypotension is common in acute care, there is a lack of accepted criteria for its definition. Most practitioners regard hypotension as undesirable even in situations that pose no immediate threat to life, but hypotension does not always lead to unfavourable outcomes based on experience and evidence. Thus efforts are needed to better understand the causes, consequences, and treatments of hypotension. This narrative review focuses on the heterogeneous underlying pathophysiological bases of hypotension and their impact on organ perfusion and patient outcomes. We propose the iso-pressure curve with hypotension and hypertension zones as a way to visualize changes in blood pressure. We also propose a haemodynamic pyramid and a pressure-output-resistance triangle to facilitate understanding of why hypotension can have different pathophysiological mechanisms and end-organ effects. We emphasise that hypotension does not always lead to organ hypoperfusion; to the contrary, hypotension may preserve or even increase organ perfusion depending on the relative changes in perfusion pressure and regional vascular resistance and the status of blood pressure autoregulation. Evidence from RCTs does not support the notion that a higher arterial blood pressure target always leads to improved outcomes. Management of blood pressure is not about maintaining a prespecified value, but rather involves ensuring organ perfusion without undue stress on the cardiovascular system.
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Innocenti F, Palmieri V, Tassinari I, Capretti E, De Paris A, Gianno A, Marchesini A, Montuori M, Pini R. Change in Myocardial Contractility in Response to Treatment with Norepinephrine in Septic Shock. Am J Respir Crit Care Med 2021; 204:365-368. [PMID: 33945774 DOI: 10.1164/rccm.202102-0442le] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Affiliation(s)
| | | | | | - Elisa Capretti
- Azienda Ospedaliero-Universitaria Careggi Firenze, Italy
| | - Anna De Paris
- Azienda Ospedaliero-Universitaria Careggi Firenze, Italy
| | - Adriana Gianno
- Azienda Ospedaliero-Universitaria Careggi Firenze, Italy
| | | | | | - Riccardo Pini
- Azienda Ospedaliero-Universitaria Careggi Firenze, Italy
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41
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Muratsu A, Hirose T, Ohnishi M, Tachino J, Nakao S, Takegawa R, Sakai T, Shiozaki T, Shimazu T. Usefulness of simultaneous measurement of brain and muscle regional oxygen saturation in shock patients: A report of three cases. Clin Case Rep 2021; 9:e04715. [PMID: 34466265 PMCID: PMC8385776 DOI: 10.1002/ccr3.4715] [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: 06/23/2021] [Revised: 07/30/2021] [Accepted: 07/31/2021] [Indexed: 11/13/2022] Open
Abstract
The regional oxygen saturation (rSO₂) values of brain and muscle tissues can be measured simultaneously even if blood pressure cannot be measured due to circulatory failure associated with shock and may continuously reflect the oxygen supply-demand balance.
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Affiliation(s)
- Arisa Muratsu
- Department of Traumatology and Acute Critical MedicineOsaka University Graduate School of MedicineSuitaJapan
| | - Tomoya Hirose
- Department of Traumatology and Acute Critical MedicineOsaka University Graduate School of MedicineSuitaJapan
| | - Mitsuo Ohnishi
- Department of Traumatology and Acute Critical MedicineOsaka University Graduate School of MedicineSuitaJapan
- Traumatology and Critical Care Medical CenterNational Hospital Organization Osaka National HospitalOsaka‐cityJapan
| | - Jotaro Tachino
- Department of Traumatology and Acute Critical MedicineOsaka University Graduate School of MedicineSuitaJapan
| | - Shunichiro Nakao
- Department of Traumatology and Acute Critical MedicineOsaka University Graduate School of MedicineSuitaJapan
| | - Ryosuke Takegawa
- Department of Traumatology and Acute Critical MedicineOsaka University Graduate School of MedicineSuitaJapan
| | - Tomohiko Sakai
- Department of Traumatology and Acute Critical MedicineOsaka University Graduate School of MedicineSuitaJapan
| | - Tadahiko Shiozaki
- Department of Traumatology and Acute Critical MedicineOsaka University Graduate School of MedicineSuitaJapan
| | - Takeshi Shimazu
- Department of Traumatology and Acute Critical MedicineOsaka University Graduate School of MedicineSuitaJapan
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Magnin M, Amson H, Vacheron CH, Thiollière F, Piriou V, Junot S, Bonnet Garin JM, Allaouchiche B. Associations between peripheral perfusion disorders, mean arterial pressure and dose of norepinephrine administrated in the early phase of septic shock. Clin Exp Pharmacol Physiol 2021; 48:1327-1335. [PMID: 34133795 DOI: 10.1111/1440-1681.13540] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 09/11/2020] [Accepted: 06/14/2021] [Indexed: 11/27/2022]
Abstract
The aim of the study was to explore the correlations between peripheral perfusion, mean arterial pressure and the dose-rate of norepinephrine (NE) infused for the treatment of septic shock. The study is retrospective analysis of data acquired prospectively on 57 patients during the first 24 hours after the occurrence of the shock. Clinical and haemodynamic characteristics, skin perfusion parameters (capillary refill time [CRT], mottling score and temperature gradients) and the dose rate of NE infusion were collected. Negative correlations between mean arterial pressure (MAP) and temperature gradients (core-to-toe: P = .03, core-to-index: P = .04) were found and abnormal CRT was associated with lower MAP (P = .02). The dose rate of NE was negatively correlated with temperature gradients (core-to-toe: P = .02, core-to-index: P = .01, forearm-to-index: P = .008) in the overall population. In patients receiving NE for at least 12 hours, the NE dose rate positively was correlated with the mottling score (P = .006), temperature gradients (core-to-toe: P = .04, forearm-to-index: P = .02, core-to-index: P = .005) and CRT (P = .001). The dose of NE administrated was associated with 14-days mortality (odds ration [OR] = 1.21 [1.06-1.38], P = .006) and with 28-days mortality (OR = 1.17 [1.01-1.36], P = 0.04). In conclusion, the study described the presence of correlations between peripheral perfusion and MAP and between peripheral perfusion and the dose rate of NE infusion.
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Affiliation(s)
- Mathieu Magnin
- University of Lyon, APCSe Agressions Pulmonaires et Circulatoires dans le Sepsis (Pulmonary and circulatory disorders in sepsis), VetAgro Sup, Marcy l'Etoile, France.,Physiology, University of Lyon, VetAgro Sup, Marcy l'Etoile, France
| | - Harry Amson
- Intensive care unit, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, University of Lyon, Pierre-Bénite, France.,PHE3ID, Centre International de Recherche en Infectiologie, Institut National de la Santé et de la Recherche Médicale U1111, CNRS UMR 5308, Université Claude Bernard Lyon 1, Lyon, France.,Service de Biostatistique - Bioinformatique, Pôle Santé Publique, Hospices Civils de Lyon, Lyon, France
| | - Charles-Hervé Vacheron
- Intensive care unit, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, University of Lyon, Pierre-Bénite, France.,PHE3ID, Centre International de Recherche en Infectiologie, Institut National de la Santé et de la Recherche Médicale U1111, CNRS UMR 5308, Université Claude Bernard Lyon 1, Lyon, France.,Service de Biostatistique - Bioinformatique, Pôle Santé Publique, Hospices Civils de Lyon, Lyon, France
| | - Fabrice Thiollière
- Intensive care unit, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, University of Lyon, Pierre-Bénite, France
| | - Vincent Piriou
- Intensive care unit, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, University of Lyon, Pierre-Bénite, France
| | - Stéphane Junot
- University of Lyon, APCSe Agressions Pulmonaires et Circulatoires dans le Sepsis (Pulmonary and circulatory disorders in sepsis), VetAgro Sup, Marcy l'Etoile, France.,Anesthesiology, University of Lyon, VetAgro Sup, Marcy l'Etoile, France
| | - Jeanne-Marie Bonnet Garin
- University of Lyon, APCSe Agressions Pulmonaires et Circulatoires dans le Sepsis (Pulmonary and circulatory disorders in sepsis), VetAgro Sup, Marcy l'Etoile, France.,Physiology, University of Lyon, VetAgro Sup, Marcy l'Etoile, France
| | - Bernard Allaouchiche
- University of Lyon, APCSe Agressions Pulmonaires et Circulatoires dans le Sepsis (Pulmonary and circulatory disorders in sepsis), VetAgro Sup, Marcy l'Etoile, France.,Intensive care unit, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, University of Lyon, Pierre-Bénite, France
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Chen H, Xu J, Wang X, Wang Y, Tong F. Early Lactate-Guided Resuscitation of Elderly Septic Patients. J Intensive Care Med 2021; 37:686-692. [PMID: 34184576 DOI: 10.1177/08850666211023347] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
BACKGROUND Early lactate-guided resuscitation was endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease the mortality of patients admitted to the ICU department with septic shock. However, its effectiveness in elderly Asian patients is uncertain. METHOD We conducted a single-center trial to test the effectiveness of the early lactate-guided resuscitation of older Asian patients at the Second Hospital of Hebei Medical University. Eligible septic shock patients who consented to participation in the study were randomly assigned to receive early lactate-guided treatment or regular treatment as controls. RESULT A total of 82 patients met the hyperlactatemia criteria and participated in the trial. Forty-two patients received early lactate-guided treatment (lactate group) and 40 received regular treatment (control group). The lactate group received more fluids at initial 6 hours (3.3 ± 1.4 vs 2.4 ± 1.7 L, P = 0.01), but similar proportions of patients in both groups required the use of vasopressors and vasodilators. Patients in the lactate group showed significantly reduced ICU needs compared to the control group, which were weaned from mechanical ventilation more quickly (median 7, IQR 4 to 14 vs median 9, IQR 4.3 to 17.8, P = 0.02) and transferred out of the ICU earlier (median 4.5, IQR 2.8 to 7.3 vs median 6, IQR 3.2 to 8, P = 0.01). However, the hospital mortality (35.7% vs 42.5%, P = 0.35) and ICU mortality (31.0% vs 37.5%, P = 0.38) for both groups were not reduced. CONCLUSION For critically ill patients (elderly Asian patients) admitted to the ICU department with hyperlactatemia, early lactate-guided treatment reduced ICU needs but did not reduce mortality.
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Affiliation(s)
- Hui Chen
- Department of Intensive Care Unit, 71213The Second Hospital of Hebei Medical University, Hebei Province, China
| | - Jiangqing Xu
- Department of Intensive Care Unit, 71213The Second Hospital of Hebei Medical University, Hebei Province, China
| | - Xia Wang
- Department of Intensive Care Unit, 71213The Second Hospital of Hebei Medical University, Hebei Province, China
| | - Yaxuan Wang
- Department of Urology Surgery, 71213The Second Hospital of Hebei Medical University, Hebei Province, China
| | - Fei Tong
- Department of Intensive Care Unit, 71213The Second Hospital of Hebei Medical University, Hebei Province, China
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Mansour C, Chaaya R, Sredensek J, Mocci R, Santangelo B, Allaouchiche B, Bonnet-Garin JMM, Boselli E, Junot SA. Evaluation of the sublingual microcirculation with sidestream dark field video microscopy in horses anesthetized for an elective procedure or intestinal surgery. Am J Vet Res 2021; 82:574-581. [PMID: 34166089 DOI: 10.2460/ajvr.82.7.574] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVE To compare the sublingual microcirculation between healthy horses anesthetized for elective procedures and horses with colic anesthetized for abdominal surgery and to determine the effect of mean arterial blood pressure (MAP) on the microcirculation. ANIMALS 9 horses in the elective group and 8 horses in the colic group. PROCEDURES Sublingual microcirculation was assessed with sidestream dark field video microscopy. Videos were captured at 3 time points during anesthesia. Recorded microvasculature parameters were De Backer score (DBS), total density of perfused vessels (PVD) and small vessels (PVD-S), total proportion of perfused vessels (PPV) and small vessels (PPV-S), vascular flow index (MFI), and heterogeneity index (HI). Blood pressure during hypotensive (MAP < 60 mm Hg) and normotensive (MAP ≥ 60 mm Hg) episodes was also recorded. RESULTS During normotensive episodes, the elective group had significantly better PPV and PPV-S versus the colic group (median PPV, 76% vs 50%; median PPV-S, 73% vs 51%). In both groups, PPV decreased during anesthesia (elective group, -29%; colic group, -16%) but significantly improved in the elective group 15 minutes before the end of anesthesia (59%). During hypotensive episodes, PVD-S was better preserved in the colic group (11.1 vs 3.8 mm/mm2). No differences were identified for the microcirculatory parameters between normo- and hypotensive episodes in the colic group. CONCLUSIONS AND CLINICAL RELEVANCE Sublingual microcirculation was better preserved in healthy horses anesthetized for elective procedures than in horses with colic anesthetized for abdominal surgery despite resuscitation maneuvers. Results indicated that the macrocirculation and microcirculation in critically ill horses may be independent.
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Affiliation(s)
- Christelle Mansour
- From the APCSe Unit UPSP 2016.A101, VetAgro Sup, University of Lyon, 69280 Marcy-l'Étoile, France
| | - Rana Chaaya
- From the Department of Pharmacology, Faculty of Agronomy and Veterinary Medicine, Lebanese University, Beirut, Lebanon
| | - Jerneja Sredensek
- From the Anesthesia Service at the Veterinary Campus of Lyon, VetAgro Sup, University of Lyon, 69280 Marcy-l'Étoile, France
| | - Rita Mocci
- From the Anesthesia Service at the Veterinary Campus of Lyon, VetAgro Sup, University of Lyon, 69280 Marcy-l'Étoile, France
| | - Bruna Santangelo
- From the Anesthesia Service at the Veterinary Campus of Lyon, VetAgro Sup, University of Lyon, 69280 Marcy-l'Étoile, France
| | - Bernard Allaouchiche
- From the APCSe Unit UPSP 2016.A101, VetAgro Sup, University of Lyon, 69280 Marcy-l'Étoile, France
- From the Lyon University Hospital Center, ICU, 69310 Pierre-Bénite, France
| | | | - Emmanuel Boselli
- From the APCSe Unit UPSP 2016.A101, VetAgro Sup, University of Lyon, 69280 Marcy-l'Étoile, France
- From the Department of Anesthesia, Hospital Center Pierre Oudot, 38300 Bourgoin-Jallieu, France
| | - Stéphane A Junot
- From the APCSe Unit UPSP 2016.A101, VetAgro Sup, University of Lyon, 69280 Marcy-l'Étoile, France
- From the Anesthesia Service at the Veterinary Campus of Lyon, VetAgro Sup, University of Lyon, 69280 Marcy-l'Étoile, France
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Effect of mean arterial pressure change by norepinephrine on peripheral perfusion index in septic shock patients after early resuscitation. Chin Med J (Engl) 2021; 133:2146-2152. [PMID: 32842018 PMCID: PMC7508439 DOI: 10.1097/cm9.0000000000001017] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background The peripheral perfusion index (PI), as a real-time bedside indicator of peripheral tissue perfusion, may be useful for determining mean arterial pressure (MAP) after early resuscitation of septic shock patients. The aim of this study was to explore the response of PI to norepinephrine (NE)-induced changes in MAP. Methods Twenty septic shock patients with pulse-induced contour cardiac output catheter, who had usual MAP under NE infusion after early resuscitation, were enrolled in this prospective, open-label study. Three MAP levels (usual MAP −10 mmHg, usual MAP, and usual MAP +10 mmHg) were obtained by NE titration, and the corresponding global hemodynamic parameters and PI were recorded. The general linear model with repeated measures was used for analysis of variance of related parameters at three MAP levels. Results With increasing NE infusion, significant changes were found in MAP (F = 502.46, P < 0.001) and central venous pressure (F = 27.45, P < 0.001) during NE titration. However, there was not a significant and consistent change in continuous cardiac output (CO) (F = 0.41, P = 0.720) and PI (F = 0.73, P = 0.482) at different MAP levels. Of the 20 patients enrolled, seven reached the maximum PI value at usual MAP −10 mmHg, three reached the maximum PI value at usual MAP, and ten reached the maximum PI value at usual MAP +10 mmHg. The change in PI was not significantly correlated with the change in CO (r = 0.260, P = 0.269) from usual MAP −10 mmHg to usual MAP. There was also no significant correlation between the change in PI and change in CO (r = 0.084, P = 0.726) from usual MAP to usual MAP +10 mmHg. Conclusions Differing MAP levels by NE infusion induced diverse PI responses in septic shock patients, and these PI responses may be independent of the change in CO. PI may have potential applications for MAP optimization based on changes in peripheral tissue perfusion.
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[S3 Guideline Sepsis-prevention, diagnosis, therapy, and aftercare : Long version]. Med Klin Intensivmed Notfmed 2021; 115:37-109. [PMID: 32356041 DOI: 10.1007/s00063-020-00685-0] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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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: 15] [Impact Index Per Article: 3.8] [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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Abstract
PURPOSE OF REVIEW The aim of this study was to discuss the implication of microvascular dysfunction in septic shock. RECENT FINDINGS Resuscitation of sepsis has focused on systemic haemodynamics and, more recently, on peripheral perfusion indices. However, central microvascular perfusion is altered in sepsis and these alterations often persist despite normalization of various macro haemodynamic resuscitative goals. Endothelial dysfunction is a key element in sepsis pathophysiology. It is responsible for the sepsis-induced hypotension. In addition, endothelial dysfunction is also implicated involved in the activation of inflammation and coagulation processes leading to amplification of the septic response and development of organ dysfunction. It also promotes an increase in permeability, mostly at venular side, and impairs microvascular perfusion and hence tissue oxygenation.Microvascular alterations are characterized by heterogeneity in blood flow distribution, with adequately perfused areas in close vicinity to not perfused areas, thus characterizing the distributive nature of septic shock. Such microvascular alterations have profound implications, as these are associated with organ dysfunction and unfavourable outcomes. Also, the response to therapy is highly variable and cannot be predicted by systemic hemodynamic assessment and hence cannot be detected by classical haemodynamic tools. SUMMARY Microcirculation is a key element in the pathophysiology of sepsis. Even if microcirculation-targeted therapy is not yet ready for the prime time, understanding the processes implicated in microvascular dysfunction is important to prevent chasing systemic hemodynamic variables when this does not contribute to improve tissue perfusion.
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49
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Roy TK, Secomb TW. Effects of impaired microvascular flow regulation on metabolism-perfusion matching and organ function. Microcirculation 2020; 28:e12673. [PMID: 33236393 DOI: 10.1111/micc.12673] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Accepted: 11/17/2020] [Indexed: 12/14/2022]
Abstract
Impaired tissue oxygen delivery is a major cause of organ damage and failure in critically ill patients, which can occur even when systemic parameters, including cardiac output and arterial hemoglobin saturation, are close to normal. This review addresses oxygen transport mechanisms at the microcirculatory scale, and how hypoxia may occur in spite of adequate convective oxygen supply. The structure of the microcirculation is intrinsically heterogeneous, with wide variations in vessel diameters and flow pathway lengths, and consequently also in blood flow rates and oxygen levels. The dynamic processes of structural adaptation and flow regulation continually adjust microvessel diameters to compensate for heterogeneity, redistributing flow according to metabolic needs to ensure adequate tissue oxygenation. A key role in flow regulation is played by conducted responses, which are generated and propagated by endothelial cells and signal upstream arterioles to dilate in response to local hypoxia. Several pathophysiological conditions can impair local flow regulation, causing hypoxia and tissue damage leading to organ failure. Therapeutic measures targeted to systemic parameters may not address or may even worsen tissue oxygenation at the microvascular level. Restoration of tissue oxygenation in critically ill patients may depend on restoration of endothelial cell function, including conducted responses.
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Affiliation(s)
- Tuhin K Roy
- Department of Anesthesiology & Perioperative Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Timothy W Secomb
- Department of Physiology, University of Arizona, Tucson, AZ, 85724, USA
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Chen J, Martin C, Ball IM, McIntyre CW, Slessarev M. Impact of Graded Passive Cycling on Hemodynamics, Cerebral Blood Flow, and Cardiac Function in Septic ICU Patients. Front Med (Lausanne) 2020; 7:569679. [PMID: 33178715 PMCID: PMC7596326 DOI: 10.3389/fmed.2020.569679] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Accepted: 08/28/2020] [Indexed: 12/19/2022] Open
Abstract
Background: In-bed passive cycling is considered a safe and feasible early mobilization technique in intensive care unit (ICU) patients who are unable to exercise actively. However, the impact of varying intensity of passive cycling on perfusion and function of ischemia-prone organs is unknown. In this study, we assessed the impact of a graded passive cycling protocol on hemodynamics, cerebral blood flow, and cardiac function in a cohort of septic ICU patients. Methods: In consecutive patients presenting with sepsis, we measured global hemodynamic indices, middle cerebral artery velocity (MCAv), and cardiac function in response to a graded increase in passive cycling cadence. Using 5-min stages, we increased cadence from 5 to 55 RPM in increments of 10 RPM, preceded and followed by 5 min baseline and recovery periods at 0 RPM. The mean values obtained during the last 2 min of each stage were compared within and between subjects for all metrics using repeated-measures ANOVA. Results: Ten septic patients (six males) completed the protocol. Across patients, there was a 5.2% reduction in MCAv from baseline at cycling cadences of 25-45 RPM with a dose-dependent decrease of MCAv of > 10% in four of the 10 patients enrolled. There was a 16% increase in total peripheral resistance from baseline at peak cadence of 55 RPMs and no changes in any other measured hemodynamic parameters. Patient responses to passive cycling varied between patients in terms of magnitude, direction of change, and the cycling cadence at which these changes occurred. Conclusions: In septic patients, graded passive cycling is associated with dose-dependent decreases in cerebral blood flow, increases in total peripheral resistance, and either improvement or worsening of left ventricular function. The magnitude and cadence threshold of these responses vary between patients. Future studies should establish whether these changes are associated with clinical outcomes, including cognitive impairment, vasopressor use, and functional outcomes.
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Affiliation(s)
- Jennifer Chen
- Department of Medical Biophysics, Western University, London, ON, Canada
| | - Claudio Martin
- Department of Medicine, Western University, London, ON, Canada
| | - Ian M Ball
- Department of Medicine, Western University, London, ON, Canada.,Departments of Epidemiology and Biostatistics, Western University, London, ON, Canada
| | - Christopher W McIntyre
- Department of Medical Biophysics, Western University, London, ON, Canada.,Department of Medicine, Western University, London, ON, Canada
| | - Marat Slessarev
- Department of Medical Biophysics, Western University, London, ON, Canada.,Department of Medicine, Western University, London, ON, Canada.,The Brain and Mind Institute, Western University, London, ON, Canada
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