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1.
Crit Care ; 23(1): 186, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31122276

RESUMO

BACKGROUND: Multiple organ dysfunction is a common cause of morbidity and mortality in intensive care units (ICUs). Original development of the Sequential Organ Failure Assessment (SOFA) score was not to predict outcome, but to describe temporal changes in organ dysfunction in critically ill patients. Organ dysfunction scoring may be a reasonable surrogate outcome in clinical trials but further exploration of the impact of case mix on the temporal sequence of organ dysfunction is required. Our aim was to compare temporal changes in SOFA scores between hospital survivors and non-survivors. METHODS: We performed a population-based observational retrospective cohort study of critically ill patients admitted from January 1, 2004, to December 31, 2013, to 4 multisystem adult intensive care units (ICUs) in Calgary, Canada. The primary outcome was temporal changes in daily SOFA scores during the first 14 days of ICU admission. SOFA scores were modeled between hospital survivors and non-survivors using generalized estimating equations (GEE) and were also stratified by admission SOFA (≤ 11 versus > 11). RESULTS: The cohort consisted of 20,007 patients with at least one SOFA score and was mostly male (58.2%) with a median age of 59 (interquartile range [IQR] 44-72). Median ICU length of stay was 3.5 (IQR 1.7-7.5) days. ICU and hospital mortality were 18.5% and 25.5%, respectively. Temporal change in SOFA scores varied by survival and admission SOFA score in a complicated relationship. Area under the receiver operating characteristic (ROC) curve using admission SOFA as a predictor of hospital mortality was 0.77. The hospital mortality rate was 5.6% for patients with an admission SOFA of 0-2 and 94.4% with an admission SOFA of 20-24. There was an approximately linear increase in hospital mortality for SOFA scores of 3-19 (range 8.7-84.7%). CONCLUSIONS: Examining the clinical course of organ dysfunction in a large non-selective cohort of patients provides insight into the utility of SOFA. We have demonstrated that hospital outcome is associated with both admission SOFA and the temporal rate of change in SOFA after admission. It is necessary to further explore the impact of additional clinical factors on the clinical course of SOFA with large datasets.


Assuntos
Insuficiência de Múltiplos Órgãos/classificação , Insuficiência de Múltiplos Órgãos/fisiopatologia , Projetos de Pesquisa/normas , Fatores de Tempo , Adulto , Idoso , Idoso de 80 Anos ou mais , Alberta , Estudos de Coortes , Feminino , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/complicações , Escores de Disfunção Orgânica , Projetos de Pesquisa/tendências , Estudos Retrospectivos , Análise de Sobrevida , Sobreviventes/estatística & dados numéricos
2.
Turk J Med Sci ; 49(2): 506-513, 2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-30997789

RESUMO

Background/aim: Intraabdominal hypertension (IAH) occurs frequently in patients with acute pancreatitis and adds to their morbidity and mortality. The main aim of the study was to identify the determination of the predictive factors connected to IAH that influence the evolution of acute pancreatitis. Materials and methods: The prospective cohort study was conducted on 100 patients who had acute pancreatitis. According to obtained intraabdominal pressure (IAP) values, the patients were divided into two groups: one group (n = 40) with normal IAP values and the other (IAH group, n = 60) with increased IAP values. Deceased patients were specially analyzed within the IAH group in order to determine mortality predictors. Results: Statistical significance of IAP (P = 0.048), lactates (P = 0.048), peak pressure (P = 0.043), abdominal perfusion pressure (P = 0.05), and mean arterial pressure (P = 0.041) was greater for deceased than for surviving patients in the IAH group. High mortality appears for patients younger than 65 years old, with lactate level higher than 3.22 mmol/L and filtration gradient (GF) lower than 67 mmHg. Conclusion: Age, lactates, GF, and APACHE II score are determined as mortality predictors for patients suffering from acute pancreatitis who developed IAH. The mortality rate is higher when the level of GF is decreasing and the level of lactate increasing.


Assuntos
Hipertensão Intra-Abdominal/mortalidade , Monitorização Fisiológica , Insuficiência de Múltiplos Órgãos/mortalidade , Pancreatite/mortalidade , Doença Aguda , Adulto , Idoso , Feminino , Humanos , Hipertensão Intra-Abdominal/fisiopatologia , Hipertensão Intra-Abdominal/terapia , Lactatos/sangue , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/fisiopatologia , Pancreatite/fisiopatologia , Pancreatite/terapia , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida
3.
Crit Rev Oncol Hematol ; 137: 18-26, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31014512

RESUMO

Multiple Myeloma (MM) is primarily a disease of old age with a median age of sixty-nine years at diagnosis. The development of novel therapies for induction and use of autologous stem cell transplantation has resulted in improved clinical outcomes and better quality of life for MM patients. Elderly patients, comprising the majority of MM population, have a higher incidence of age-related comorbidities, frailty and organ dysfunction which complicates the coordination of treatment and limits the selection of therapies. Even in the era of multiple chemotherapeutic options, the clinical heterogeneity of the myeloma patients' demands personalized treatments which often require dose-adjustments or dose delays. The use of reduced-dose regimens and various comorbidity indices has improved clinical outcome and regimen tolerability in MM patients with renal, neurological and bone abnormalities. We focus on advancements in the treatment of multiple myeloma with the goal to guide clinicians towards patient-specific management.


Assuntos
Mieloma Múltiplo/terapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Comorbidade , Fragilidade/fisiopatologia , Humanos , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/fisiopatologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Medicina de Precisão/métodos , Qualidade de Vida , Transplante de Células-Tronco
4.
Am J Physiol Lung Cell Mol Physiol ; 316(5): L946-L952, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30840483

RESUMO

Patients who survive the acute phase of sepsis can progress to persistent inflammation, immunosuppression, and catabolism syndrome (PICS). Although sepsis is characterized by early hypercoagulability and delayed hypocoagulability, coagulopathy during chronic critical illness is not fully understood. The objective of this study was to determine whether sepsis-induced PICS is associated with coagulation abnormalities. Using our previously described murine PICS model, outbred mice underwent cecal ligation and puncture, and coagulability was characterized after 8 days. We found that during PICS the spleen became markedly enlarged with increased splenocytes and splenic megakaryocytes without a concomitant increase in circulating platelets. Microscopy revealed a nearly sevenfold increase in pulmonary microvascular thrombi in PICS mice, along with significantly decreased pulmonary tidal volumes and inspiratory times and with significantly increased respiratory rates. Thromboelastometry showed that PICS mice had significantly delayed clot initiation time but increased clot firmness. Finally, PICS mice displayed delayed thrombin production and decreased overall thrombin concentrations. All together, these data demonstrate a general dysregulation of coagulation resulting in microthrombus formation and compromised lung function. On the basis of these findings, we propose that consumptive coagulopathy constitutes another cardinal feature of PICS and may contribute to the ongoing tissue damage and multiple organ failure that can occur in chronic critical illness.


Assuntos
Coagulação Intravascular Disseminada , Pulmão , Insuficiência de Múltiplos Órgãos , Sepse , Animais , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/etiologia , Coagulação Intravascular Disseminada/patologia , Coagulação Intravascular Disseminada/fisiopatologia , Pulmão/irrigação sanguínea , Pulmão/metabolismo , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Camundongos , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/patologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Sepse/sangue , Sepse/complicações , Sepse/patologia , Sepse/fisiopatologia
5.
Eur J Gastroenterol Hepatol ; 31(5): 618-625, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30920976

RESUMO

INTRODUCTION: Microcirculation is essential for adequate tissue perfusion and organ function. Microcirculatory changes may occur in cirrhosis, inducing loss of multiorgan function. The aim was to evaluate preliver transplantation and postliver transplantation aspects of multiorgan function, microcirculation, inflammatory, and endothelial biomarkers and survival in a controlled study including cirrhotic outpatients. PATIENTS AND METHODS: We accessed functional capillary density (FCD) and red blood cell acceleration (RBCA) by nailfold videocapillaroscopy. Inflammatory and endothelial biomarkers [interleukin-6 (IL-6), soluble intercellular adhesion molecule-1, endothelin-1, and tumor necrosis factor-α] were analyzed. Cerebral and renal functions were assessed to represent organ dysfunction and regression analyses were carried out. Receiver operating characteristic curves were constructed and survival Kaplan-Meier analysis was carried out. RESULTS: Fifty-four patients and 18 controls were included. Inflammatory and endothelial markers increased in advanced disease. FCD was reduced and RBCA was progressively lower according to disease severity. RBCA correlated inversely with inflammatory and endothelial biomarkers, and directly with renal function. The presence of hepatic encephalopathy correlated inversely with RBCA and directly with IL-6 and endothelin-1. In multivariate analysis, RBCA was an independent factor for organ dysfunction. The area under the receiver operating chartacteristic curve for IL-6 for survival was 0.74 (0.59-0.89), P=0.05. Transplant-free survival was 97.5% for values under 5.78 ng/ml (IL-6 best cutoff) and 83.9% above 5.78 ng/ml, log-rank=0.018. Eleven patients underwent transplantation, with an overall improvement in microcirculatory function. CONCLUSION: Our results suggest a mechanism of organ damage in cirrhosis, where microcirculatory dysfunction could be correlated to inflammatory and endothelial biomarkers, and loss of multiorgan function. IL-6 seems to be an important survival marker of inflammation. Liver transplantation improved microcirculatory dysfunction, corroborating this hypothesis.


Assuntos
Capilares/fisiopatologia , Cirrose Hepática/complicações , Microcirculação , Insuficiência de Múltiplos Órgãos/etiologia , Unhas/irrigação sanguínea , Idoso , Biomarcadores/sangue , Capilares/diagnóstico por imagem , Estudos de Casos e Controles , Eritrócitos , Feminino , Encefalopatia Hepática/sangue , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/fisiopatologia , Humanos , Mediadores da Inflamação/sangue , Molécula 1 de Adesão Intercelular/sangue , Interleucina-6/sangue , Nefropatias/sangue , Nefropatias/etiologia , Nefropatias/fisiopatologia , Cirrose Hepática/sangue , Cirrose Hepática/fisiopatologia , Cirrose Hepática/cirurgia , Transplante de Fígado , Estudos Longitudinais , Masculino , Angioscopia Microscópica , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/fisiopatologia , Fluxo Sanguíneo Regional , Fatores de Risco , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue
6.
Zhonghua Shao Shang Za Zhi ; 35(3): 161-162, 2019 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-30897860

RESUMO

Objective: A series of pathophysiological changes occur in a body with burn, among which the pathophysiological changes in organs are rather insidious but have far-reaching effects. At present, in clinical practice, we mainly adopt symptomatic or alternative treatment to deal with organ dysfunction, lacking systematic intervention measures based on clear and perfect theoretical data. Theme of the key article of this issue is the injury and protection of organs in the early stage after burns. The collected articles show the current status and frontiers of the research on this topic in China, including the retrospective analysis of clinical data, exploration of cell-level injury mechanism, and experimental treatment scheme in animal models. However, until now, few instructive or inspiring articles have been published. I appeal more colleagues could focus on this, explore more, research more, and share more.


Assuntos
Queimaduras/complicações , Queimaduras/patologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Animais , China , Rim/fisiopatologia , Fígado/fisiopatologia , Pulmão/fisiopatologia , Insuficiência de Múltiplos Órgãos/etiologia , Estudos Retrospectivos
7.
Zhonghua Shao Shang Za Zhi ; 35(3): 163-168, 2019 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-30897861

RESUMO

Objective: To analyze the clinical characteristics of early organ injury in elderly patients with severe burns and the effects on the prognosis of patients. Methods: From January 2010 to August 2018, 62 patients with severe burns (43 men and 19 women, aged from 60 to 89 years at the time of admission) who were hospitalized in the Institute of Burn Research of the First Affiliated Hospital of Army Medical University (the Third Military Medical University, hereinafter referred to as the author's affiliation), meeting the inclusion criteria, were included in elderly (E) group, and 124 patients with severe burns (86 men and 38 women, aged from 18 to 59 years at the time of admission) at the same term were included in young and middle-aged (YM) group. Treatment of patients in the 2 groups followed the conventional procedures of the author's affiliation. The following data of patients in the 2 groups were retrospectively analyzed. (1) Fluid replacement volume and urine volume within the first and second post injury hour (PIH) 24 were recorded. The levels of hemoglobin, haematocrit, and blood lactic acid at admission, PIH 24 and 48 were recorded. (2) The creatine kinase isozyme-MB (CK-MB), total bilirubin, blood creatinine, oxygenation index, and blood platelet count at admission, at shock stage, and on post injury day (PID) 3 to 7 were collected. (3) The days of seriously or critically ill and deaths were recorded. Data were processed with chi-square test, group t test, Mann-Whitney U test, analysis of variance for repeated measurement, and Bonferroni correction. Results: (1) There were no statistically significant differences in fluid replacement volume within the first and second PIH 24, and urine volume within the second PIH 24 between patients in the 2 groups (t=0.351, 1.307, 1.110, P>0.05). The urine volume of patients in group E within the first PIH 24 was significantly less than that in group YM (t=5.628, P<0.05). There were no statistically significant differences in levels of hemoglobin (t=0.011, 1.075, 0.239), haematocrit (t=0, 0.033, 0.199), and blood lactic acid (t=0.017, 1.002, 0.739) at admission, PIH 24 and 48 between patients in the 2 groups (P>0.05). (2) There were no statistically significant differences in levels of CK-MB at admission and on PID 3 to 7 between patients in the 2 groups (t=0.069, 0.001, P>0.05). The level of CK-MB of patients in group E at shock stage was significantly higher than that in group YM (t=4.017, P<0.05). There were no statistically significant differences in levels of total bilirubin at admission and on PID 3 to 7 between patients in the 2 groups (t=0.227, 0.002, P>0.05). However, the level of total bilirubin of patients in group E at shock stage was significantly higher than that in group YM (t=6.485, P<0.05). The levels of blood creatinine of patients in group E at admission and shock stage were significantly higher than those in group YM (t=4.226, 12.299, P<0.05 or P<0.01), while there was no statistically significant difference between them on PID 3 to 7 (t=0.693, P>0.05). The oxygenation indexes of patients in group E at admission and shock stage and on PID 3 to 7 [(371±16), (263±16), and (228±18) mmHg (1 mmHg=0.133 kPa)] were lower than (420±13), (327±13), and (281±17) mmHg of patients in group YM, respectively (t=5.650, 9.782, 4.856, P<0.05 or P<0.01). There were no statistically significant differences in levels of blood platelet count at admission and shock stage between patients in the 2 groups (t=0.038, 0.588, P>0.05), while the level of blood platelet count of patients in group E on PID 3 to 7 was significantly lower than that in group YM (t=6.636, P<0.05). (3) The days of seriously or critically ill and death rate of patients in group E were respectively longer or higher than those in group YM (Z=-2.303, χ(2)=13.676, P<0.05 or P<0.01). Conclusions: In the case of the same tissue perfusion at shock stage, injuries in heart, liver, kidney, lung, and coagulation system in elderly patients with severe burns are more obvious than those in young and middle-aged patients, with more severe illness and higher mortality.


Assuntos
Queimaduras/complicações , Insuficiência de Múltiplos Órgãos/fisiopatologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto Jovem
8.
PLoS One ; 14(3): e0213085, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30835764

RESUMO

INTRODUCTION: Previous studies described impaired microvascular perfusion and tissue oxygenation as reliable predictors of Multiple Organ Failure in major trauma. However, this relationship has been incompletely investigated. The objective of this analysis is to further evaluate the association between organ dysfunction and microcirculation after trauma. MATERIALS AND METHODS: This is a retrospective subgroup analysis on 28 trauma patients enrolled for the Microcirculation DAIly MONitoring in critically ill patients study (NCT 02649088). Patients were divided in two groups according with their Sequential Organ Failure Assessment (SOFA) score at day 4. At admission and every 24 hours, the sublingual microcirculation was evaluated with Sidestream Darkfield Imaging (SDF) and peripheral tissue perfusion was assessed with Near Infrared Spectroscopy (NIRS) and Vascular Occlusion Test (VOT). Simultaneously, hemodynamic, clinical/laboratory parameters and main organ supports were collected. RESULTS: Median SOFA score at Day 4 was 6.5. Accordingly, patients were divided in two groups: D4-SOFA ≤6.5 and D4-SOFA >6.5. The Length of Stay in Intensive Care was significantly higher in patients with D4-SOFA>6.5 compared to D4-SOFA≤6.5 (p = 0.013). Total Vessel Density of small vessels was significantly lower in patients with high D4-SOFA score at Day 1 (p = 0.002) and Day 2 (p = 0.006) after admission; the Perfused Vessel Density was lower in patients with high D4-SOFA score at Day 1 (p = 0.007) and Day 2 (p = 0.033). At Day 1, NIRS monitoring with VOT showed significantly faster tissue oxygen saturation downslope (p = 0.018) and slower upslope (p = 0.04) in patients with high D4-SOFA. DISCUSSION: In our cohort of major traumas, sublingual microcirculation and peripheral microvascular reactivity were significantly more impaired early after trauma in those patients who developed more severe organ dysfunctions. Our data would support the hypothesis that restoration of macrocirculation can be dissociated from restoration of peripheral and tissue perfusion, and that microvascular alterations can be associated with organ failure.


Assuntos
Microcirculação , Soalho Bucal/irrigação sanguínea , Insuficiência de Múltiplos Órgãos/diagnóstico , Ferimentos e Lesões/complicações , Adulto , Idoso , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Escores de Disfunção Orgânica , Consumo de Oxigênio , Estudos Prospectivos , Estudos Retrospectivos , Espectroscopia de Luz Próxima ao Infravermelho , Ferimentos e Lesões/fisiopatologia
9.
Crit Care ; 23(1): 83, 2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30867011

RESUMO

BACKGROUND: Continuous coordination among organ systems is necessary to maintain biological stability in humans. Organ system network analysis in addition to organ-oriented medicine is expected to improve patient outcomes. However, organ system networks remain beyond clinical application with little evidence for their importance on homeostatic mechanisms. This proof-of-concept study examined the impact of organ system networks on systemic stability in severely ill patients. METHODS: Patients admitted to the intensive care unit of the University of Tokyo Hospital with one representative variable reflecting the condition of each of the respiratory, cardiovascular, renal, hepatic, coagulation, and inflammatory systems were enrolled. Relationships among the condition of individual organ systems, inter-organ connections, and systemic stability were evaluated between non-survivors and survivors whose organ system conditions were matched to those of the non-survivors (matched survivors) as well as between non-survivors and all survivors. We clustered these six organ systems using principal component analysis and compared the dispersion of the principal component scores of each cluster using the Ansari-Bradley test to evaluate systemic stability involving multiple organ systems. Inter-organ connections were evaluated using Spearman's rank test. RESULTS: Among a total of 570 enrolled patients, 91 patients died. The principal component analysis yielded the respiratory-renal-inflammatory and cardiovascular-hepatic-coagulation system clusters. In the respiratory-renal-inflammatory cluster, organ systems were connected in both the survivors and the non-survivors. The principal component scores of the respiratory-renal-inflammatory cluster were dispersed similarly (stable cluster) in the non-survivors, the matched survivors, and the total survivors irrespective of the severity of individual organ system dysfunction. Conversely, in the cardiovascular-hepatic-coagulation cluster, organ systems were connected only in the survivors, and the principal component scores of the cluster were significantly dispersed (unstable cluster) in the non-survivors compared to the total survivors (P = 0.002) and the matched survivors (P = 0.004). CONCLUSIONS: This study demonstrated that systemic instability was closely associated with network disruption among organ systems irrespective of their dysfunction severity. Organ system network analysis is necessary to improve outcomes in severely ill patients.


Assuntos
Insuficiência de Múltiplos Órgãos/diagnóstico , APACHE , Idoso , Biomarcadores/análise , Biomarcadores/sangue , Estado Terminal/epidemiologia , Estado Terminal/terapia , Feminino , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/fisiopatologia , Escores de Disfunção Orgânica , Análise de Componente Principal
10.
Gastroenterology ; 156(7): 2008-2023, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30768987

RESUMO

Acute pancreatitis may be associated with both local and systemic complications. Systemic injury manifests in the form of organ failure, which is seen in approximately 20% of all cases of acute pancreatitis and defines "severe acute pancreatitis." Organ failure typically develops early in the course of acute pancreatitis, but also may develop later due to infected pancreatic necrosis-induced sepsis. Organ failure is the most important determinant of outcome in acute pancreatitis. We review here the current understanding of the risk factors, pathophysiology, timing, impact on outcome, and therapy of organ failure in acute pancreatitis. As we discuss the pathophysiology of severe systemic injury, the distinctions between markers and mediators of severity are highlighted based on evidence supporting their causality in organ failure. Emphasis is placed on clinically relevant end points of organ failure and the mechanisms underlying the pathophysiological perturbations, which offer insight into potential therapeutic targets to treat.


Assuntos
Insuficiência de Múltiplos Órgãos/etiologia , Pancreatite/complicações , Doença Aguda , Animais , Humanos , Insuficiência de Múltiplos Órgãos/mortalidade , Insuficiência de Múltiplos Órgãos/fisiopatologia , Insuficiência de Múltiplos Órgãos/terapia , Pancreatite/mortalidade , Pancreatite/fisiopatologia , Pancreatite/terapia , Prognóstico , Medição de Risco , Fatores de Risco
11.
Int J Artif Organs ; 42(6): 315-317, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30614343

RESUMO

PURPOSE: For the first time in Kazakhstan, we have used a combined extracorporeal support, by including the CytoSorb system in a continuous veno-venous hemofiltration system in an 8-month-old patient with a body weight of 5600 g. RESULTS: The CytoSorb therapy session resulted in a reduction of inflammation markers IL-6, S100, procalcitonin, and C-reactive protein. Simultaneously, the level of transaminases, creatine kinase, and troponin were normalized, by the end of the session patient hemodynamics were stable and there was no need for vasopressors, acid-base balance was maintained, and the patient was weaned from mechanical ventilation to spontaneous breathing. CONCLUSION: Treatment using the CytoSorb device was safe and well-tolerated in a pediatric patient and has proven its practical value as an adjuvant therapy for sepsis in pediatric patient populations.


Assuntos
Biomarcadores , Hemofiltração , Insuficiência de Múltiplos Órgãos , Choque Séptico , Equilíbrio Ácido-Base , Biomarcadores/análise , Biomarcadores/sangue , Proteína C-Reativa/análise , Terapia Combinada/métodos , Hemodinâmica , Hemofiltração/instrumentação , Hemofiltração/métodos , Humanos , Lactente , Interleucina-6/sangue , Cazaquistão , Masculino , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Insuficiência de Múltiplos Órgãos/terapia , Pró-Calcitonina/sangue , Diálise Renal/efeitos adversos , Respiração Artificial/métodos , Proteínas S100/sangue , Choque Séptico/sangue , Choque Séptico/fisiopatologia , Choque Séptico/terapia , Transaminases/sangue , Resultado do Tratamento
12.
Am J Physiol Renal Physiol ; 316(3): F438-F448, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30516423

RESUMO

Sepsis-induced organ failure is characterized by a massive inflammatory response and oxidative stress. Acute kidney injury (AKI) occurs in approximately half of patients in septic shock, and the mortality associated with sepsis-induced AKI is unacceptably high. Klotho is a protein expressed by renal cells and has anti-senescence properties. Klotho has also been shown to protect the kidneys in ischemia-reperfusion injury and to have antioxidant properties. To analyze the role of Klotho in sepsis-related organ dysfunction and AKI, we used a cecal ligation and puncture (CLP) model of sepsis in heterozygous Klotho-haploinsufficient mice and their wild-type littermates (CLP- Kl/+ and CLP-WT mice, respectively). In comparison with the CLP-WT mice, CLP- Kl/+ mice showed lower survival, impaired renal function, impaired hepatic function, greater oxidative stress, upregulation of inflammatory pathways (at the systemic and kidney tissue levels), and increased NF-κB activation. It is noteworthy that CLP- Kl/+ mice also showed lower heart-rate variability, less sympathetic activity, impaired baroreflex sensitivity to sodium nitroprusside, and a blunted blood pressure response to phenylephrine. We also demonstrated that sepsis creates a state of acute Klotho deficiency. Given that low Klotho expression exacerbates sepsis and multiple organ dysfunction, Klotho might play a protective role in sepsis, especially in elderly individuals in whom Klotho expression is naturally reduced.


Assuntos
Glucuronidase/metabolismo , Rim/metabolismo , Fígado/metabolismo , Insuficiência de Múltiplos Órgãos/metabolismo , Sepse/metabolismo , Animais , Barorreflexo/fisiologia , Ceco/lesões , Modelos Animais de Doenças , Glucuronidase/genética , Haploinsuficiência , Frequência Cardíaca/fisiologia , Inflamação/metabolismo , Inflamação/fisiopatologia , Rim/fisiopatologia , Fígado/fisiopatologia , Camundongos , Camundongos Knockout , Insuficiência de Múltiplos Órgãos/genética , Insuficiência de Múltiplos Órgãos/fisiopatologia , NF-kappa B/metabolismo , Estresse Oxidativo/fisiologia , Sepse/genética , Sepse/fisiopatologia , Regulação para Cima
13.
Br J Biomed Sci ; 76(1): 29-34, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30379116

RESUMO

OBJECTIVE: An imbalance in oxidant-antioxidant status may impact the severity of sepsis. We hypothesised links between nitrosative stress and pro-inflammatory cytokines and their correlation with the severity of sepsis and associated organ dysfunction. METHODS: The hypothesis was tested in 110 patients with sepsis (in whom a disease severity score (APACHE II) and assessment of organ failure score (SOFA) were determined) and 55 healthy volunteers. Neutrophil inducible nitric oxide synthase (iNOS) expressions at mRNA and protein levels were estimated by real-time PCR and immuno-precipitation followed by Western blotting, respectively. Nitric oxide (NO) content was assessed in neutrophils by confocal microscopy, plasma nitrite by the Griess reaction and inflammatory cytokines (TNF-α, IFN-γ and IL-8) by ELISA (in plasma) and real-time PCR (in neutrophils). Serum bilirubin and creatinine were determined by routine methods and lung function by the PaO2/FiO2 ratio. RESULTS: Increased neutrophil iNOS expression and NO content, plasma total nitrite content and pro-inflammatory cytokines were present in sepsis patients (all P < 0.001). Plasma nitrite correlated with cytokines, APACHE II, SOFA, PaO2/FiO2 ratio, serum bilirubin and creatinine clearance (all r2 0.63-0.85, P < 0.001). Cytokines correlated with nitrite, APACHE II, SOFA, PaO2/FiO2 ratio, serum bilirubin and creatinine clearance (all r2 0.35-0.85, P < 0.001). CONCLUSION: Neutrophils iNOS expression, NO content, plasma nitrite and cytokines have a role in the assessment of the severity of sepsis and organ toxicity.


Assuntos
Interferon gama/sangue , Interleucina-8/sangue , Insuficiência de Múltiplos Órgãos/diagnóstico , Estresse Nitrosativo , Sepse/diagnóstico , Fator de Necrose Tumoral alfa/sangue , APACHE , Adulto , Idoso , Bilirrubina/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Creatinina/sangue , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/fisiopatologia , Neutrófilos/metabolismo , Neutrófilos/patologia , Óxido Nítrico/sangue , Óxido Nítrico Sintase Tipo II/sangue , Óxido Nítrico Sintase Tipo II/genética , Sepse/sangue , Sepse/fisiopatologia
14.
J Int Med Res ; 47(1): 66-75, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30179058

RESUMO

OBJECTIVE: This study aimed to examine the relationship between serum iron levels and in-hospital mortality in critically ill patients. METHODS: We retrospectively studied 250 critically ill patients who received treatment at the intensive care unit between June 2015 and May 2017. Blood chemistry and hepatic and renal function were measured. Kaplan-Meier survival curves were plotted according to serum iron levels. Correlations between serum iron levels and other variables were analyzed. RESULTS: A total of 165 (66.0%) patients had abnormally low serum iron levels (<10.6 µmol/L). Patients who died during hospitalization had markedly higher Acute Physiology and Chronic Health Evaluation II scores and significantly lower serum iron levels compared with those who survived. Cumulative survival was significantly lower in patients with low serum iron levels than in those with normal serum iron levels in subgroup analysis of older patients (n = 192). Multivariate regression analysis showed that, after adjusting for relevant factors, low serum iron levels remained an independent risk for in-hospital mortality (odds ratio 2.014; 95% confidence interval 1.089, 3.725). CONCLUSIONS: Low serum iron levels are present in a significant proportion of critically ill patients and are associated with higher in-hospital mortality, particularly in older patients.


Assuntos
Mortalidade Hospitalar/tendências , Ferro/sangue , Insuficiência de Múltiplos Órgãos/mortalidade , Infarto do Miocárdio/mortalidade , Pneumonia/mortalidade , Acidente Vascular Cerebral/mortalidade , Idoso , Biomarcadores/sangue , Estado Terminal , Feminino , Humanos , Unidades de Terapia Intensiva , Testes de Função Renal , Tempo de Internação/estatística & dados numéricos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/fisiopatologia , Análise Multivariada , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/fisiopatologia , Pneumonia/sangue , Pneumonia/diagnóstico , Pneumonia/fisiopatologia , Prognóstico , Estudos Retrospectivos , Escala Psicológica Aguda Simplificada , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Análise de Sobrevida
15.
Ann Vasc Surg ; 56: 354.e5-354.e9, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30500643

RESUMO

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is being considered for temporizing catastrophic hemorrhage before arriving at a specialty center for definitive surgical management. CASE: We describe the clinical case of a 72-year-old male with a ruptured infrarenal aortic abdominal aneurysm initially stabilized with REBOA at an outside facility and transferred to our care. Transport time was >100 minutes. Despite successful surgical repair of the ruptured aneurysm, the patient expired from multiple-organ failure likely related to ischemia-reperfusion injuries from prolonged balloon occlusion of the aorta. CONCLUSIONS: Ischemia-mitigating techniques and therapies need to improve drastically before the clinical application of REBOA can be effectively extended to outside the vicinity of specialty centers.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Ruptura Aórtica/cirurgia , Oclusão com Balão/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Insuficiência de Múltiplos Órgãos/etiologia , Traumatismo por Reperfusão/etiologia , Ressuscitação/efeitos adversos , Idoso , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/fisiopatologia , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/fisiopatologia , Aortografia/métodos , Angiografia por Tomografia Computadorizada , Evolução Fatal , Humanos , Masculino , Insuficiência de Múltiplos Órgãos/fisiopatologia , Traumatismo por Reperfusão/fisiopatologia , Ressuscitação/métodos , Fatores de Tempo , Resultado do Tratamento
16.
Gut ; 68(6): 1044-1051, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-29950344

RESUMO

OBJECTIVE: In patients with pancreatitis, early persisting organ failure is believed to be the most important cause of mortality. This study investigates the relation between the timing (onset and duration) of organ failure and mortality and its association with infected pancreatic necrosis in patients with necrotising pancreatitis. DESIGN: We performed a post hoc analysis of a prospective database of 639 patients with necrotising pancreatitis from 21 hospitals. We evaluated the onset, duration and type of organ failure (ie, respiratory, cardiovascular and renal failure) and its association with mortality and infected pancreatic necrosis. RESULTS: In total, 240 of 639 (38%) patients with necrotising pancreatitis developed organ failure. Persistent organ failure (ie, any type or combination) started in the first week in 51% of patients with 42% mortality, in 13% during the second week with 46% mortality and in 36% after the second week with 29% mortality. Mortality in patients with persistent multiple organ failure lasting <1 week, 1-2 weeks, 2-3 weeks or longer than 3 weeks was 43%, 38%, 46% and 52%, respectively (p=0.68). Mortality was higher in patients with organ failure alone than in patients with organ failure and infected pancreatic necrosis (44% vs 29%, p=0.04). However, when excluding patients with very early mortality (within 10 days of admission), patients with organ failure with or without infected pancreatic necrosis had similar mortality rates (28% vs 34%, p=0.33). CONCLUSION: In patients with necrotising pancreatitis, early persistent organ failure is not associated with increased mortality when compared with persistent organ failure which develops further on during the disease course. Furthermore, no association was found between the duration of organ failure and mortality.


Assuntos
Causas de Morte , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Pancreatite Necrosante Aguda/complicações , Adulto , Idoso , Estudos de Coortes , Bases de Dados Factuais , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/fisiopatologia , Pancreatite Necrosante Aguda/mortalidade , Pancreatite Necrosante Aguda/patologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Estatísticas não Paramétricas , Análise de Sobrevida , Fatores de Tempo
17.
J Intensive Care Med ; 34(6): 486-494, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28372498

RESUMO

PURPOSE: Sepsis stimulates pro- and anti-inflammatory immune responses. The innate immune response is critical to organ injury repair. We tested for an association between innate immune function and organ function recovery in a prospective cohort of immune-competent adults with sepsis. METHODS: We conducted a prospective observational cohort study enrolling immune-competent adults with sepsis. We tested innate immune function by quantification of lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) α production capacity in whole blood samples on hospital days 1, 4, and 6. The primary outcome was organ function recovery on day 4 defined as a 4-point decrease in the composite cardiovascular and respiratory Sequential Organ Failure Assessment (SOFA) score components or a SOFA score ≤2. RESULTS: Patients with sepsis who recovered organ function by day 4 (n = 11) had similar baseline characteristics when compared to those with ongoing organ failure (n = 13). Tumor necrosis factor α production capacity was similar between the 2 groups on hospital days 1 and 4 but significantly different on day 6. Patients who regained organ function recovery had significantly higher TNF-α production capacity on day 6 ( P = .01), which persisted after adjustment for age, Acute Physiology and Chronic Health Evaluation III score, and steroid administration ( P = .03). There was no difference in TNF-α production capacity over time in those who survived to hospital discharge versus nonsurvivors. CONCLUSION: Increasing TNF-α production capacity is associated with improved organ failure recovery. Further studies are needed to evaluate a causal association between innate immune suppression and organ failure recovery as well as predictive accuracy for hospital survival. Impaired TNF-α production as a marker of sepsis-associated innate immune dysfunction may be a feasible target for immune stimulation to decrease time to organ failure recovery.


Assuntos
Cuidados Críticos , Imunidade Inata/imunologia , Insuficiência de Múltiplos Órgãos/imunologia , Sepse/imunologia , Biomarcadores/sangue , Humanos , Imunidade Inata/fisiologia , Unidades de Terapia Intensiva , Contagem de Linfócitos , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/fisiopatologia , Insuficiência de Múltiplos Órgãos/terapia , Escores de Disfunção Orgânica , Estudos Prospectivos , Sepse/sangue , Sepse/fisiopatologia , Sepse/terapia
18.
Eur J Trauma Emerg Surg ; 45(2): 255-261, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29318345

RESUMO

PURPOSE: Patients with multiple injuries are particularly susceptible to accidental hypothermia which is correlated with an increased risk of post-traumatic complications and mortality; however, its impact on neurological outcome in cases where there is concomitant traumatic brain injury is underexplored. METHODS: We analyzed severely injured patients (ISS ≥ 16) including a moderate-to-severe traumatic brain injury (AISHead ≥ 3). The primary endpoint was objective neurological recovery, expressed as Glasgow Outcome Scale (GOS) score at time of discharge. Secondary endpoints were mortality, systemic inflammatory response syndrome (SIRS), sepsis, acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS). Statistical analysis included logistic regression (odds ratio). The significance level in all analyses was p = 0.05. RESULTS: We analyzed 278 patients (M age = 43 years, SD 19; M ISS = 32.8, SD 10.7). Mortality was 17% (n = 14). 102 patients (37%) were hypothermic on admission. Hypothermic patients were more severely injured (ISS 35.6 ± 11.1 vs. 31.2 ± 10.1, p = 0.001; APACHE II 18.1 ± 7.4 vs. 16.2 ± 7.3, p = 0.045) and had a higher transfusion requirement. Mortality rate in hypothermic patients was increased (23.5 vs. 13.1%, p = 0.03); however, hypothermia was not an independent predictor of mortality. Median GOS at discharge was 3 (IQR 3); in 47% of patients the outcome was favorable (GOS 4 or 5) and 36% it was poor (GOS 2 or 3). There were no differences in post-traumatic complications. Analysis of 73 matched pairs of hypothermic and normothermic patients could not prove hypothermia as an independent predictor of poor neurological outcome (OR 1.7, 95% CI 0.8-3.6, p = 0.1) in the total population. However, older patients (> 41 years) had a 4.2-times higher risk (95% CI 1.4-12.7; p = 0.01) of poor neurological outcome, if they were hypothermic on admission. CONCLUSIONS: Accidental hypothermia seems to have a negative impact on neurological recovery in older patients with multiple injuries including traumatic brain injury which outweighs potential benefits.


Assuntos
Lesões Encefálicas Traumáticas/fisiopatologia , Hipotermia/fisiopatologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Doenças Neurodegenerativas/fisiopatologia , Síndrome do Desconforto Respiratório do Adulto/fisiopatologia , Sepse/fisiopatologia , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Adulto , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/mortalidade , Feminino , Humanos , Hipotermia/etiologia , Hipotermia/mortalidade , Escala de Gravidade do Ferimento , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/mortalidade , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/mortalidade , Prognóstico , Síndrome do Desconforto Respiratório do Adulto/mortalidade , Sepse/mortalidade , Síndrome de Resposta Inflamatória Sistêmica/mortalidade , Fatores de Tempo , Adulto Jovem
19.
J Formos Med Assoc ; 118(5): 859-866, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-29798818

RESUMO

Despite supportive care with renal replacement therapy, acute kidney injury (AKI) remains linked with increased short and long-term mortality, not just because of renal failure but also because of accompanying remote organ dysfunction. Increasing evidence from animal studies suggests that numerous factors contribute both to the development of AKI and the impairment of various vital organs, including pro-inflammatory cytokine expression, leukocyte infiltration, vascular permeability changes, ion channel derangement, oxidative stress, and cell apoptosis. Human studies have reported that AKI with concomitant multi-organ dysfunction is associated with a high death rate. We propose that persistent organ dysfunction after AKI can be considered in relation to three proposed mechanisms (1) classical uremic stress and its associated sequelae (2) systemic inflammation as a consequence of kidney injury (3) treatment-related effects. Using this framework, we discuss the known pathways through which AKI can affect the function of a number of remote organs. We review the short- and long-term clinical impact of AKI on other organ systems and potential mechanisms through which AKI may affect remote organ systems. Further elucidating the effects of AKI on remote organ function may lead to new therapeutic strategies to improve outcomes after AKI.


Assuntos
Lesão Renal Aguda/complicações , Efeitos Adversos de Longa Duração/fisiopatologia , Insuficiência de Múltiplos Órgãos/etiologia , Terapia de Substituição Renal/efeitos adversos , Lesão Renal Aguda/mortalidade , Lesão Renal Aguda/fisiopatologia , Animais , Apoptose , Citocinas/metabolismo , Humanos , Inflamação/fisiopatologia , Efeitos Adversos de Longa Duração/mortalidade , Insuficiência de Múltiplos Órgãos/mortalidade , Insuficiência de Múltiplos Órgãos/fisiopatologia
20.
BMJ Case Rep ; 11(1)2018 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-30567262

RESUMO

Hyperthyroidism is a common metabolic disorder, although its presentation as an endocrine emergency called thyroid storm is rare. Here we review a case of a thyroid storm as the initial presentation of thyrotoxicosis, with multiple organ failure and haemodynamic collapse due to low-output cardiac dysfunction. Quick intervention with aggressive antithyroid therapy, including steroid pulse, and supportive intensive care measures led to an outstanding improvement and full recovery. The present case clearly shows the beneficial impact of initial clinical suspicion resulting in an early diagnosis and intensive therapy. Moreover, it supports the additional role of steroids to aggressive antithyroid strategy in order to control associated deleterious systemic inflammatory reactions.


Assuntos
Antitireóideos/uso terapêutico , Cuidados Críticos , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Choque Cardiogênico/tratamento farmacológico , Esteroides/uso terapêutico , Crise Tireóidea/tratamento farmacológico , Disfunção Ventricular Esquerda/tratamento farmacológico , Anticolesterolemiantes/uso terapêutico , Resina de Colestiramina/uso terapêutico , Cuidados Críticos/métodos , Frequência Cardíaca , Hemodinâmica , Humanos , Iodetos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Propiltiouracila/uso terapêutico , Choque Cardiogênico/etiologia , Choque Cardiogênico/fisiopatologia , Crise Tireóidea/complicações , Crise Tireóidea/fisiopatologia , Resultado do Tratamento , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia , Perda de Peso
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