Pub Date : 2015-12-01DOI: 10.1097/SHK.0000000000000481
I. Rasmy, H. Mohamed, N. Nabil, S. Abdalah, A. Hasanin, A. Eladawy, M. Ahmed, A. Mukhtar
ABSTRACT We evaluated the ability of perfusion index (PI) to predict vasopressor requirement during early resuscitation in patients with severe sepsis. All consecutive patients with clinically suspected severe sepsis as defined by the criteria of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference were included. Perfusion variables included PI, arterial lactate level, central venous oxygen saturation, and the difference between central venous carbon dioxide and arterial carbon dioxide pressures, and were recorded before resuscitation and 6 h thereafter. We enrolled 36 patients with severe sepsis. Twenty-one patients required vasopressors, whereas 15 did not. The cut-off of the PI value for predicting vasopressor requirement was ⩽0.3. This cut-off value had a sensitivity of 100% and a specificity of 93%; the area under the curve was 0.96 (95% confidence interval 0.8–0.99, P < 0.0001). The cut-off of the arterial lactate level for predicting vasopressor requirement was ≥1.8 mg dL−1. This cut-off value had a sensitivity of 82% and a specificity of 80%; the area under the curve was 0.84 (95% confidence interval 0.68–0.94, P < 0.0001). Other perfusion variables failed to predict vasopressor requirement in patients with severe sepsis. We concluded that PI and arterial lactate level are good predictors of vasopressor requirement during early resuscitation in patients with severe sepsis. Further studies are warranted to investigate whether monitoring PI during resuscitation improves the outcome of patients with septic shock.
{"title":"Evaluation of Perfusion Index as a Predictor of Vasopressor Requirement in Patients with Severe Sepsis","authors":"I. Rasmy, H. Mohamed, N. Nabil, S. Abdalah, A. Hasanin, A. Eladawy, M. Ahmed, A. Mukhtar","doi":"10.1097/SHK.0000000000000481","DOIUrl":"https://doi.org/10.1097/SHK.0000000000000481","url":null,"abstract":"ABSTRACT We evaluated the ability of perfusion index (PI) to predict vasopressor requirement during early resuscitation in patients with severe sepsis. All consecutive patients with clinically suspected severe sepsis as defined by the criteria of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference were included. Perfusion variables included PI, arterial lactate level, central venous oxygen saturation, and the difference between central venous carbon dioxide and arterial carbon dioxide pressures, and were recorded before resuscitation and 6 h thereafter. We enrolled 36 patients with severe sepsis. Twenty-one patients required vasopressors, whereas 15 did not. The cut-off of the PI value for predicting vasopressor requirement was ⩽0.3. This cut-off value had a sensitivity of 100% and a specificity of 93%; the area under the curve was 0.96 (95% confidence interval 0.8–0.99, P < 0.0001). The cut-off of the arterial lactate level for predicting vasopressor requirement was ≥1.8 mg dL−1. This cut-off value had a sensitivity of 82% and a specificity of 80%; the area under the curve was 0.84 (95% confidence interval 0.68–0.94, P < 0.0001). Other perfusion variables failed to predict vasopressor requirement in patients with severe sepsis. We concluded that PI and arterial lactate level are good predictors of vasopressor requirement during early resuscitation in patients with severe sepsis. Further studies are warranted to investigate whether monitoring PI during resuscitation improves the outcome of patients with septic shock.","PeriodicalId":21787,"journal":{"name":"Shock: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches","volume":"2011 1","pages":"554–559"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86343365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-12-01DOI: 10.1097/SHK.0000000000000461
R. Petroni, P. Biselli, T. M. Lima, I. Velasco, F. Soriano
ABSTRACT Acute lung injury (ALI) is a common complication associated with septic shock that directly influences the prognosis of sepsis patients. Currently, one of the main supportive treatment modalities for septic shock is fluid resuscitation. The use of hypertonic saline (HS: 7.5% NaCl) for fluid resuscitation has been described as a promising therapy in experimental models of sepsis-induced ALI, but it has failed to produce similar results in clinical practice. Thus, we compared experimental timing versus clinical timing effectiveness (i.e., early vs. late fluid resuscitation) after the inflammatory scenario was established in a rat model of bacterial lipopolysaccharide-induced ALI. We found that late fluid resuscitation with hypertonic saline (NaCl 7.5%) did not reduce the mortality rates of animals compared with the mortality late associated with early treatment. Late fluid resuscitation with both hypertonic and normal saline increased pulmonary inflammation, decreased pulmonary function, and induced pulmonary injury by elevating metalloproteinase-2 and metalloproteinase-9 activity and collagen deposition in the animals, unlike early treatment. The animals with lipopolysaccharide-induced ALI that received late resuscitation with any kind of fluids demonstrated aggravated pulmonary injury and respiratory function. Moreover, we showed that the therapeutic window for a beneficial effect of fluid resuscitation with hypertonic saline is very narrow.
{"title":"Impact of Time on Fluid Resuscitation with Hypertonic Saline (NaCl 7.5%) in Rats with LPS-Induced Acute Lung Injury","authors":"R. Petroni, P. Biselli, T. M. Lima, I. Velasco, F. Soriano","doi":"10.1097/SHK.0000000000000461","DOIUrl":"https://doi.org/10.1097/SHK.0000000000000461","url":null,"abstract":"ABSTRACT Acute lung injury (ALI) is a common complication associated with septic shock that directly influences the prognosis of sepsis patients. Currently, one of the main supportive treatment modalities for septic shock is fluid resuscitation. The use of hypertonic saline (HS: 7.5% NaCl) for fluid resuscitation has been described as a promising therapy in experimental models of sepsis-induced ALI, but it has failed to produce similar results in clinical practice. Thus, we compared experimental timing versus clinical timing effectiveness (i.e., early vs. late fluid resuscitation) after the inflammatory scenario was established in a rat model of bacterial lipopolysaccharide-induced ALI. We found that late fluid resuscitation with hypertonic saline (NaCl 7.5%) did not reduce the mortality rates of animals compared with the mortality late associated with early treatment. Late fluid resuscitation with both hypertonic and normal saline increased pulmonary inflammation, decreased pulmonary function, and induced pulmonary injury by elevating metalloproteinase-2 and metalloproteinase-9 activity and collagen deposition in the animals, unlike early treatment. The animals with lipopolysaccharide-induced ALI that received late resuscitation with any kind of fluids demonstrated aggravated pulmonary injury and respiratory function. Moreover, we showed that the therapeutic window for a beneficial effect of fluid resuscitation with hypertonic saline is very narrow.","PeriodicalId":21787,"journal":{"name":"Shock: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches","volume":"1 1","pages":"609–615"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90449025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-12-01DOI: 10.1097/SHK.0000000000000462
L. Martin, Carsten Peters, S. Schmitz, J. Moellmann, Antons Martincuks, N. Heussen, M. Lehrke, G. Müller-Newen, G. Marx, T. Schuerholz
ABSTRACT The heart is one of the most frequently affected organs in sepsis. Recent studies focused on lipopolysaccharide-induced mitochondrial dysfunction; however myocardial dysfunction is not restricted to gram-negative bacterial sepsis. The purpose of this study was to investigate circulating heparan sulfate (HS) as an endogenous danger associated molecule causing cardiac mitochondrial dysfunction in sepsis. We used an in vitro model with native sera (SsP) and sera eliminated from HS (HS-free), both of septic shock patients, to stimulate murine cardiomyocytes. As determined by extracellular flux analyzing, SsP increased basal mitochondrial respiration, but reduced maximum mitochondrial respiration, compared with unstimulated cells (P < 0.0001 and P < 0.0001, respectively). Cells stimulated with HS-free serum revealed unaltered basal and maximum mitochondrial respiration, compared with unstimulated cells (P = 0.1174 and P = 0.8992, respectively). Cellular ATP-level were decreased in SsP-stimulated cells but unaltered in cells stimulated with HS-free serum compared with unstimulated cells (P < 0.0001 and P = 0.1593, respectively). Live-cell imaging revealed an increased production of mitochondrial reactive oxygen species in cells stimulated with SsP compared with cells stimulated with HS-free serum (P < 0.0001). Expression of peroxisome proliferator-activated receptors (PPAR&agr; and PPAR&ggr;) and their co-activators PGC-1&agr;, which regulate mitochondrial function, were studied using PCR. Cells stimulated with SsP showed downregulated PPARs and PGC-1&agr; mRNA-levels compared with HS-free serum (P = 0.0082, P = 0.0128, and P = 0.0185, respectively). Blocking Toll-like receptor 4 revealed an inhibition of HS-dependent downregulation of PPARs and PGC-1&agr; (all P < 0.0001). In conclusion, circulating HS in serum of septic shock patients cause cardiac mitochondrial dysfunction, suggesting that HS may be targets of therapeutics in septic cardiomyopathy.
{"title":"Soluble Heparan Sulfate in Serum of Septic Shock Patients Induces Mitochondrial Dysfunction in Murine Cardiomyocytes","authors":"L. Martin, Carsten Peters, S. Schmitz, J. Moellmann, Antons Martincuks, N. Heussen, M. Lehrke, G. Müller-Newen, G. Marx, T. Schuerholz","doi":"10.1097/SHK.0000000000000462","DOIUrl":"https://doi.org/10.1097/SHK.0000000000000462","url":null,"abstract":"ABSTRACT The heart is one of the most frequently affected organs in sepsis. Recent studies focused on lipopolysaccharide-induced mitochondrial dysfunction; however myocardial dysfunction is not restricted to gram-negative bacterial sepsis. The purpose of this study was to investigate circulating heparan sulfate (HS) as an endogenous danger associated molecule causing cardiac mitochondrial dysfunction in sepsis. We used an in vitro model with native sera (SsP) and sera eliminated from HS (HS-free), both of septic shock patients, to stimulate murine cardiomyocytes. As determined by extracellular flux analyzing, SsP increased basal mitochondrial respiration, but reduced maximum mitochondrial respiration, compared with unstimulated cells (P < 0.0001 and P < 0.0001, respectively). Cells stimulated with HS-free serum revealed unaltered basal and maximum mitochondrial respiration, compared with unstimulated cells (P = 0.1174 and P = 0.8992, respectively). Cellular ATP-level were decreased in SsP-stimulated cells but unaltered in cells stimulated with HS-free serum compared with unstimulated cells (P < 0.0001 and P = 0.1593, respectively). Live-cell imaging revealed an increased production of mitochondrial reactive oxygen species in cells stimulated with SsP compared with cells stimulated with HS-free serum (P < 0.0001). Expression of peroxisome proliferator-activated receptors (PPAR&agr; and PPAR&ggr;) and their co-activators PGC-1&agr;, which regulate mitochondrial function, were studied using PCR. Cells stimulated with SsP showed downregulated PPARs and PGC-1&agr; mRNA-levels compared with HS-free serum (P = 0.0082, P = 0.0128, and P = 0.0185, respectively). Blocking Toll-like receptor 4 revealed an inhibition of HS-dependent downregulation of PPARs and PGC-1&agr; (all P < 0.0001). In conclusion, circulating HS in serum of septic shock patients cause cardiac mitochondrial dysfunction, suggesting that HS may be targets of therapeutics in septic cardiomyopathy.","PeriodicalId":21787,"journal":{"name":"Shock: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches","volume":"100 1","pages":"569–577"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80763513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-12-01DOI: 10.1097/SHK.0000000000000465
N. Hara, M. Chijiiwa, M. Yara, Y. Ishida, Yukihiko Ogiwara, M. Inazu, M. Kuroda, M. Karlsson, F. Sjovall, E. Elmér, H. Uchino
ABSTRACT The pathophysiology of sepsis-associated encephalopathy (SAE) is complex and remains incompletely elucidated. Dysregulated reactive oxygen species (ROS) production and mitochondrial-mediated necrotic–apoptotic pathway have been proposed as part of the pathogenesis. The present study aimed at analyzing the preventive effect of the free radical scavenger edaravone on sepsis-induced brain alterations. Sepsis was induced by cecal ligation and puncture (CLP) and the mice were divided into three groups—CLP vehicle (CLPV), CLP and edaravone (MCI-186, 3-methyl-1-phenyl-2-pyrazolin-5-one) (CLPE), and sham-operated (Sham). Mice in CLPV and CLPE were injected with saline or edaravone intraperitoneally at a dose of 10 mg/kg twice daily. The treatments were initiated 4 days prior to the surgical procedure. Mortality, histological changes, electron microscopy (EM), and expression of Bcl-2 family genes (Bcl-2 and Bax) were analyzed in selected brain regions. CLPE showed significant improvement in survival compared with CLPV 18 h postinduction of sepsis (P < 0.05). At the same time point, pathohistological analysis also showed marked reduction of neuronal cell death in both parietal cortex and hippocampus in the CLPE (P < 0.05). RT-PCR and immunoblotting directed at the Bcl-2 family revealed increased Bax mRNA levels in hippocampus at 12 h in CLPV as well as an increased Bax/Bcl-2 protein ratio, changes that were significantly suppressed in CLPE. In conclusion, our study suggests that sepsis induced by cecal ligation alters cerebral redox status and supports a proapoptotic phenotype. The free radical scavenger edavarone reduces mortality of septic mice and protects against sepsis-induced neuronal cell death.
{"title":"Metabolomic Analyses of Brain Tissue in Sepsis Induced by Cecal Ligation Reveal Specific Redox Alterations—Protective Effects of the Oxygen Radical Scavenger Edaravone","authors":"N. Hara, M. Chijiiwa, M. Yara, Y. Ishida, Yukihiko Ogiwara, M. Inazu, M. Kuroda, M. Karlsson, F. Sjovall, E. Elmér, H. Uchino","doi":"10.1097/SHK.0000000000000465","DOIUrl":"https://doi.org/10.1097/SHK.0000000000000465","url":null,"abstract":"ABSTRACT The pathophysiology of sepsis-associated encephalopathy (SAE) is complex and remains incompletely elucidated. Dysregulated reactive oxygen species (ROS) production and mitochondrial-mediated necrotic–apoptotic pathway have been proposed as part of the pathogenesis. The present study aimed at analyzing the preventive effect of the free radical scavenger edaravone on sepsis-induced brain alterations. Sepsis was induced by cecal ligation and puncture (CLP) and the mice were divided into three groups—CLP vehicle (CLPV), CLP and edaravone (MCI-186, 3-methyl-1-phenyl-2-pyrazolin-5-one) (CLPE), and sham-operated (Sham). Mice in CLPV and CLPE were injected with saline or edaravone intraperitoneally at a dose of 10 mg/kg twice daily. The treatments were initiated 4 days prior to the surgical procedure. Mortality, histological changes, electron microscopy (EM), and expression of Bcl-2 family genes (Bcl-2 and Bax) were analyzed in selected brain regions. CLPE showed significant improvement in survival compared with CLPV 18 h postinduction of sepsis (P < 0.05). At the same time point, pathohistological analysis also showed marked reduction of neuronal cell death in both parietal cortex and hippocampus in the CLPE (P < 0.05). RT-PCR and immunoblotting directed at the Bcl-2 family revealed increased Bax mRNA levels in hippocampus at 12 h in CLPV as well as an increased Bax/Bcl-2 protein ratio, changes that were significantly suppressed in CLPE. In conclusion, our study suggests that sepsis induced by cecal ligation alters cerebral redox status and supports a proapoptotic phenotype. The free radical scavenger edavarone reduces mortality of septic mice and protects against sepsis-induced neuronal cell death.","PeriodicalId":21787,"journal":{"name":"Shock: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches","volume":"11 1","pages":"578–584"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78320575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-12-01DOI: 10.1097/SHK.0000000000000480
J. Janak, Jeffrey T. Howard, K. Goei, Rachael N Weber, Gary W. Muniz, C. Hinojosa-Laborde, V. Convertino
Introduction: As technological advances allow for the development of more sophisticated measurement of the mechanisms that contribute to compensation for loss of circulating blood volume such as hemorrhage, it is important to compare the discriminative ability of these new measures to standard vital signs and other new physiologic metrics of interest. The purpose of this study was to compare the discriminative ability of the following three measures to predict the onset of hemodynamic decompensation: peripheral perfusion index (PPI), pulse pressure variability (PPV), and the compensatory reserve index (CRI). Materials and Methods: There were 51 healthy participants who underwent a progressive simulated hemorrhage to induce central hypovolemia by lower body negative pressure (LBNP). The least-squares means and 95% confidence intervals for each measure were reported by LBNP level and stratified by tolerance status (high tolerance vs. low tolerance). Generalized estimating equations were used to perform repeated measures logistic regression analysis by regressing the onset of hemodynamic decompensation on each of the vital signs of interest. These probabilities were used to calculate sensitivity, specificity, and receiver-operating characteristic area under the curve (ROCAUC) for PPI, PPV, and CRI. Results: Compared with both PPV (ROCAUC = 0.79) and PPI (0.56), the CRI (0.90) had superior discriminative ability (P ⩽ 0.0001) to predict the onset of hemodynamic decompensation. This included higher sensitivity (0.86 vs. 0.78 and 0.71) and specificity (0.78 vs. 0.69 and 0.29) for the CRI compared with PPV and PPI, respectively. Further, CRI was the only measure with mean predicted probabilities of the onset of hemodynamic decompensation that progressively increased as the level of simulated hemorrhage increased. Discussion: There are two potential rationales for why the CRI had superior discriminative ability to predict hemodynamic decompensation. First, the CRI more accurately predicted the onset of hemodynamic decompensation at all levels of simulated hemorrhage, but especially at lower levels of hemorrhage. Second, the CRI was better able to differentiate high versus low tolerant participants. Conclusion: Consistent with previous research, the CRI had superior discriminative ability to predict the onset of hemodynamic decompensation. For those patients at greatest risk for developing impending circulatory shock, identifying the most sensitive and specific measures of the onset of hemodynamic decompensation is critical for both the early recognition and implementation of life-saving interventions.
导论:随着技术的进步，可以开发出更复杂的测量方法来补偿循环血容量损失(如出血)的机制，将这些新测量方法与标准生命体征和其他感兴趣的新生理指标的鉴别能力进行比较是很重要的。本研究的目的是比较以下三种指标预测血流动力学失代偿发生的判别能力:外周灌注指数(PPI)、脉压变异性(PPV)和代偿储备指数(CRI)。材料和方法:51名健康受试者接受进行性模拟出血，通过下体负压(LBNP)诱导中枢性低血容量。每个测量值的最小二乘平均值和95%置信区间按LBNP水平报告，并按耐受性状态(高耐受性vs低耐受性)分层。通过回归每个感兴趣的生命体征的血流动力学失代偿的开始，使用广义估计方程进行重复测量逻辑回归分析。这些概率用于计算PPI、PPV和CRI的敏感性、特异性和受体操作特征曲线下面积(ROCAUC)。结果:与PPV (ROCAUC = 0.79)和PPI(0.56)相比，CRI(0.90)在预测血流动力学失代偿发生方面具有更强的判别能力(P≤0.0001)。与PPV和PPI相比，CRI分别具有更高的敏感性(0.86 vs. 0.78和0.71)和特异性(0.78 vs. 0.69和0.29)。此外，CRI是唯一具有血流动力学失代偿发生的平均预测概率的指标，该概率随着模拟出血水平的增加而逐渐增加。讨论:CRI在预测血流动力学失代偿方面具有优越的判别能力，可能有两个原因。首先，CRI更准确地预测了所有水平的模拟出血的血流动力学失代偿的发生，但特别是在低水平的出血。其次，CRI能够更好地区分高耐受性和低耐受性的参与者。结论:与既往研究一致，CRI对血流动力学失代偿的发生有较好的判别能力。对于那些发生即将发生的循环性休克风险最大的患者，确定血液动力学失代偿发生的最敏感和最具体的措施对于早期识别和实施挽救生命的干预措施至关重要。
{"title":"Predictors of the Onset of Hemodynamic Decompensation During Progressive Central Hypovolemia: Comparison of the Peripheral Perfusion Index, Pulse Pressure Variability, and Compensatory Reserve Index","authors":"J. Janak, Jeffrey T. Howard, K. Goei, Rachael N Weber, Gary W. Muniz, C. Hinojosa-Laborde, V. Convertino","doi":"10.1097/SHK.0000000000000480","DOIUrl":"https://doi.org/10.1097/SHK.0000000000000480","url":null,"abstract":"Introduction: As technological advances allow for the development of more sophisticated measurement of the mechanisms that contribute to compensation for loss of circulating blood volume such as hemorrhage, it is important to compare the discriminative ability of these new measures to standard vital signs and other new physiologic metrics of interest. The purpose of this study was to compare the discriminative ability of the following three measures to predict the onset of hemodynamic decompensation: peripheral perfusion index (PPI), pulse pressure variability (PPV), and the compensatory reserve index (CRI). Materials and Methods: There were 51 healthy participants who underwent a progressive simulated hemorrhage to induce central hypovolemia by lower body negative pressure (LBNP). The least-squares means and 95% confidence intervals for each measure were reported by LBNP level and stratified by tolerance status (high tolerance vs. low tolerance). Generalized estimating equations were used to perform repeated measures logistic regression analysis by regressing the onset of hemodynamic decompensation on each of the vital signs of interest. These probabilities were used to calculate sensitivity, specificity, and receiver-operating characteristic area under the curve (ROCAUC) for PPI, PPV, and CRI. Results: Compared with both PPV (ROCAUC = 0.79) and PPI (0.56), the CRI (0.90) had superior discriminative ability (P ⩽ 0.0001) to predict the onset of hemodynamic decompensation. This included higher sensitivity (0.86 vs. 0.78 and 0.71) and specificity (0.78 vs. 0.69 and 0.29) for the CRI compared with PPV and PPI, respectively. Further, CRI was the only measure with mean predicted probabilities of the onset of hemodynamic decompensation that progressively increased as the level of simulated hemorrhage increased. Discussion: There are two potential rationales for why the CRI had superior discriminative ability to predict hemodynamic decompensation. First, the CRI more accurately predicted the onset of hemodynamic decompensation at all levels of simulated hemorrhage, but especially at lower levels of hemorrhage. Second, the CRI was better able to differentiate high versus low tolerant participants. Conclusion: Consistent with previous research, the CRI had superior discriminative ability to predict the onset of hemodynamic decompensation. For those patients at greatest risk for developing impending circulatory shock, identifying the most sensitive and specific measures of the onset of hemodynamic decompensation is critical for both the early recognition and implementation of life-saving interventions.","PeriodicalId":21787,"journal":{"name":"Shock: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches","volume":"8 1","pages":"548–553"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88913214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-12-01DOI: 10.1097/SHK.0000000000000456
B. Ramakers, E. Giamarellos‐Bourboulis, Chronis Tasioudis, M. Coenen, M. Kox, S. Vermeulen, Johanne M. Groothuismink, J. G. van der Hoeven, C. Routsi, A. Savva, A. Prekates, F. Diamantea, D. Sinapidis, P. Smits, K. Toutouzas, N. Riksen, P. Pickkers
Introduction: Adenosine exerts anti-inflammatory and tissue-protective effects during systemic inflammation. While the tissue-protective effects might limit organ damage, its anti-inflammatory properties may induce immunoparalysis and impede bacterial clearance. The common 34C>T loss-of-function variant of AMPD1 (rs17602729) is associated with increased adenosine formation, but effects on immune function and outcome in sepsis patients are unknown. Methods: The effects of the presence of the 34C>T variant on sepsis susceptibility, immune function, multi-organ dysfunction, and mortality in septic patients were studied. Patients suffering from community acquired pneumonia (CAP, initial cohort n = 285; replication cohort n = 212) and ventilator-associated pneumonia (VAP, n = 117; n = 33) and control patients without infection (n = 101) were enrolled. Genetic distributions of the AMPD1 SNP were CC 76%, CT 22%, and TT 2% in the initial cohort and CC 80%, CT 18%, and TT 2% in the replication cohort. Results: The occurrence of septic CAP, but not septic VAP, was increased for the CT versus CC genotype (OR (95% CI) 2.0 (1.1–3.7); P = 0.02) in the initial cohort. The increased risk for the CT versus CC genotype was also observed in the replication cohort but did not reach statistical significance there (P = 0.38), resulting in an OR of the total group of 1.7 (95% CI 1.0–3.1), P = 0.07. In septic patients carrying the CT genotype, the ex vivo production of TNF-&agr; by LPS-stimulated monocytes was attenuated (P = 0.005), indicative of a more pronounced immunoparalytic state in these patients. Conclusions: Presence of the AMPD1 34C>T variant is associated with higher infection susceptibility to CAP, but not to VAP. More pronounced immunoparalysis in these patients mediated by the anti-inflammatory effects of adenosine may account for this observation.
{"title":"Effects of the 34C>T Variant of the AMPD1 Gene on Immune Function, Multi-Organ Dysfunction, and Mortality in Sepsis Patients","authors":"B. Ramakers, E. Giamarellos‐Bourboulis, Chronis Tasioudis, M. Coenen, M. Kox, S. Vermeulen, Johanne M. Groothuismink, J. G. van der Hoeven, C. Routsi, A. Savva, A. Prekates, F. Diamantea, D. Sinapidis, P. Smits, K. Toutouzas, N. Riksen, P. Pickkers","doi":"10.1097/SHK.0000000000000456","DOIUrl":"https://doi.org/10.1097/SHK.0000000000000456","url":null,"abstract":"Introduction: Adenosine exerts anti-inflammatory and tissue-protective effects during systemic inflammation. While the tissue-protective effects might limit organ damage, its anti-inflammatory properties may induce immunoparalysis and impede bacterial clearance. The common 34C>T loss-of-function variant of AMPD1 (rs17602729) is associated with increased adenosine formation, but effects on immune function and outcome in sepsis patients are unknown. Methods: The effects of the presence of the 34C>T variant on sepsis susceptibility, immune function, multi-organ dysfunction, and mortality in septic patients were studied. Patients suffering from community acquired pneumonia (CAP, initial cohort n = 285; replication cohort n = 212) and ventilator-associated pneumonia (VAP, n = 117; n = 33) and control patients without infection (n = 101) were enrolled. Genetic distributions of the AMPD1 SNP were CC 76%, CT 22%, and TT 2% in the initial cohort and CC 80%, CT 18%, and TT 2% in the replication cohort. Results: The occurrence of septic CAP, but not septic VAP, was increased for the CT versus CC genotype (OR (95% CI) 2.0 (1.1–3.7); P = 0.02) in the initial cohort. The increased risk for the CT versus CC genotype was also observed in the replication cohort but did not reach statistical significance there (P = 0.38), resulting in an OR of the total group of 1.7 (95% CI 1.0–3.1), P = 0.07. In septic patients carrying the CT genotype, the ex vivo production of TNF-&agr; by LPS-stimulated monocytes was attenuated (P = 0.005), indicative of a more pronounced immunoparalytic state in these patients. Conclusions: Presence of the AMPD1 34C>T variant is associated with higher infection susceptibility to CAP, but not to VAP. More pronounced immunoparalysis in these patients mediated by the anti-inflammatory effects of adenosine may account for this observation.","PeriodicalId":21787,"journal":{"name":"Shock: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches","volume":"47 1","pages":"542–547"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84755564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ABSTRACT Sepsis is common in intensive care units (ICU) and is associated with high mortality. Cardiac dysfunction complicating sepsis is one of the most important causes of this mortality. This dysfunction is due to myocardial inflammation and reduced production of energy by the heart. A number of studies have shown that hydrogen-rich saline (HRS) has a beneficial effect on sepsis. Therefore, we tested whether HRS prevents cardiac dysfunction by increasing cardiac energy. Four groups of rats received intraperitoneal injections of one of the following solutions: normal saline (NS), HRS, lipopolysaccharide (LPS), and LPS plus HRS. Cardiac function was measured by echocardiography 8 h after the injections. Gene and protein expression related to fatty acid oxidation (FAO) were measured by quantitative polymerase chain reaction (PCR) and Western blot analysis. The injection of LPS compromised heart function through decreased fractional shortening (FS) and increased left ventricular diameter (LVD). The addition of HRS increased FS, palmitate triphosphate, and the ratio of phosphocreatinine (PCr) to adenosine triphosphate (ATP) as well as decreasing LVD. The LPS challenge reduced the expression of genes related to FAO, including perioxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1&agr;), perioxisome proliferator-activated receptor alpha (PPAR&agr;), Estrogen-related receptor alpha (ERR&agr;), and their downstream targets, in mRNA and protein level, which were attenuated by HRS. However, HRS had little effect on glucose metabolism. Furthermore, HRS inhibited c-Jun N-terminal kinase (JNK) activation in the rat heart. Inhibition of JNK by HRS showed beneficial effects on LPS-challenged rats, at least in part, by restoring cardiac FAO.
{"title":"Hydrogen-Rich Saline Attenuates Lipopolysaccharide-Induced Heart Dysfunction by Restoring Fatty Acid Oxidation in Rats by Mitigating C-Jun N-Terminal Kinase Activation","authors":"Bing-dong Tao, Lidan Liu, Nian-hong Wang, Dong-yi Tong, Wei Wang, Jin Zhang","doi":"10.1097/SHK.0000000000000467","DOIUrl":"https://doi.org/10.1097/SHK.0000000000000467","url":null,"abstract":"ABSTRACT Sepsis is common in intensive care units (ICU) and is associated with high mortality. Cardiac dysfunction complicating sepsis is one of the most important causes of this mortality. This dysfunction is due to myocardial inflammation and reduced production of energy by the heart. A number of studies have shown that hydrogen-rich saline (HRS) has a beneficial effect on sepsis. Therefore, we tested whether HRS prevents cardiac dysfunction by increasing cardiac energy. Four groups of rats received intraperitoneal injections of one of the following solutions: normal saline (NS), HRS, lipopolysaccharide (LPS), and LPS plus HRS. Cardiac function was measured by echocardiography 8 h after the injections. Gene and protein expression related to fatty acid oxidation (FAO) were measured by quantitative polymerase chain reaction (PCR) and Western blot analysis. The injection of LPS compromised heart function through decreased fractional shortening (FS) and increased left ventricular diameter (LVD). The addition of HRS increased FS, palmitate triphosphate, and the ratio of phosphocreatinine (PCr) to adenosine triphosphate (ATP) as well as decreasing LVD. The LPS challenge reduced the expression of genes related to FAO, including perioxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1&agr;), perioxisome proliferator-activated receptor alpha (PPAR&agr;), Estrogen-related receptor alpha (ERR&agr;), and their downstream targets, in mRNA and protein level, which were attenuated by HRS. However, HRS had little effect on glucose metabolism. Furthermore, HRS inhibited c-Jun N-terminal kinase (JNK) activation in the rat heart. Inhibition of JNK by HRS showed beneficial effects on LPS-challenged rats, at least in part, by restoring cardiac FAO.","PeriodicalId":21787,"journal":{"name":"Shock: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches","volume":"89 1","pages":"593–600"},"PeriodicalIF":0.0,"publicationDate":"2015-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85600057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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