Dissociation between sublingual and gut microcirculation in the response to a fluid challenge in postoperative patients with abdominal sepsis

Results: Fluid administration increased the cardiac index (2.6 ± 0.5 vs. 3.3 ± 1.0 L/min/m2, P < 0.01) and mean arterial blood pressure (68 ± 11 vs. 82 ± 12 mm Hg, P < 0.0001). The sublingual but not the intestinal red blood cell (RBC) velocity increased (912 ± 270 vs. 1,064 ± 200 μm/s, P < 0.002 and 679 ± 379 vs. 747 ± 419 μm/s, P = 0.12, respectively). The sublingual and intestinal perfused vascular density (PVD) did not change significantly (15.2 ± 2.9 vs. 16.1 ± 1.2 mm/mm2 and 12.3 ± 6.7 vs. 13.0 ± 6.7 mm/mm2). We found no correlation between the basal sublingual and intestinal RBC velocities or between their changes in response to the fluid challenge. The individual changes in sublingual RBC velocity correlated with those in cardiac index and basal RBC velocity. Individual changes in intestinal RBC velocity did not correlate with either the cardiac index modifications or the basal RBC velocity. The same pattern was observed with the sublingual and the intestinal PVDs. The sublingual RBC velocities and PVDs were similar between survivors and nonsurvivors. But the intestinal RBC velocities and PVDs were lower in nonsurvivors.Conclusions: In this series of postoperative septic patients, we found a dissociation between sublingual and intestinal microcirculation. The improvement in the sublingual microcirculation after fluid challenge was dependent on the basal state and the increase in cardiac output. In contrast, the intestinal microcirculation behaved as an isolated territory.Methods: Twenty-two septic patients in the first postoperative day of an intestinal surgery, in which an ostomy had been constructed, were evaluated both before and 20 min after a challenge of 10 mL/kg of 6% hydroxyethylstarch 130/0.4. We measured systemic hemodynamics and sublingual and intestinal microcirculation. Correlations between variables were determined through the Pearson test.Background: This study was performed to compare intestinal and sublingual microcirculation and their response to a fluid challenge.Facultad de Ciencias Médica

Dissociation between sublingual and gut microcirculation in the response to a fluid challenge in postoperative patients with abdominal sepsis

Results: Fluid administration increased the cardiac index (2.6 ± 0.5 vs. 3.3 ± 1.0 L/min/m2, P < 0.01) and mean arterial blood pressure (68 ± 11 vs. 82 ± 12 mm Hg, P < 0.0001). The sublingual but not the intestinal red blood cell (RBC) velocity increased (912 ± 270 vs. 1,064 ± 200 μm/s, P < 0.002 and 679 ± 379 vs. 747 ± 419 μm/s, P = 0.12, respectively). The sublingual and intestinal perfused vascular density (PVD) did not change significantly (15.2 ± 2.9 vs. 16.1 ± 1.2 mm/mm2 and 12.3 ± 6.7 vs. 13.0 ± 6.7 mm/mm2). We found no correlation between the basal sublingual and intestinal RBC velocities or between their changes in response to the fluid challenge. The individual changes in sublingual RBC velocity correlated with those in cardiac index and basal RBC velocity. Individual changes in intestinal RBC velocity did not correlate with either the cardiac index modifications or the basal RBC velocity. The same pattern was observed with the sublingual and the intestinal PVDs. The sublingual RBC velocities and PVDs were similar between survivors and nonsurvivors. But the intestinal RBC velocities and PVDs were lower in nonsurvivors.Conclusions: In this series of postoperative septic patients, we found a dissociation between sublingual and intestinal microcirculation. The improvement in the sublingual microcirculation after fluid challenge was dependent on the basal state and the increase in cardiac output. In contrast, the intestinal microcirculation behaved as an isolated territory.Methods: Twenty-two septic patients in the first postoperative day of an intestinal surgery, in which an ostomy had been constructed, were evaluated both before and 20 min after a challenge of 10 mL/kg of 6% hydroxyethylstarch 130/0.4. We measured systemic hemodynamics and sublingual and intestinal microcirculation. Correlations between variables were determined through the Pearson test.Background: This study was performed to compare intestinal and sublingual microcirculation and their response to a fluid challenge.Facultad de Ciencias Médica

Incremento da depuração renal em pacientes gravemente enfermos: Incidência, fatores associados e efeitos no tratamento com vancomicina

Objective: An augmented renal clearance has been described in some groups of critically ill patients, and it might induce sub-optimal concentrations of drugs eliminated by glomerular filtration, mainly antibiotics. Studies on its occurrence and determinants are lacking. Our goals were to determine the incidence and associated factors of augmented renal clearance and the efects on vancomycin concentrations and dosing in a series of intensive care unit patients. Methods: We prospectively studied 363 patients admitted during 1 year to a clinical-surgical intensive care unit. Patients with serum creatinine >1.3mg/dL were excluded. Creatinine clearance was calculated from a 24-hour urine collection. Patients were grouped according to the presence of augmented renal clearance (creatinine clearance >120mL/min/1.73m2), and possible risk factors were analyzed with bivariate and logistic regression analysis. In patients treated with vancomycin, dosage and plasma concentrations were registered. Results: Augmented renal clearance was present in 103 patients (28%); they were younger (48±15 versus 65±17 years, p>0.0001), had more frequent obstetric (16 versus 7%, p=0.0006) and trauma admissions (10 versus 3%, p=0.016) and fewer comorbidities. The only independent determinants for the development of augmented renal clearance were age (OR 0.95; p<0.0001; 95%CI 0.93-0.96) and absence of diabetes (OR 0.34; p=0.03; 95%CI 0.12-0.92). Twelve of the 46 patients who received vancomycin had augmented renal clearance and despite higher doses, had lower concentrations. Conclusions: In this cohort of critically ill patients, augmented renal clearance was a common finding. Age and absence of diabetes were the only independent determinants. Therefore, younger and previously healthy patients might require larger vancomycin dosing.Facultad de Ciencias Médica

Incremento da depuração renal em pacientes gravemente enfermos: Incidência, fatores associados e efeitos no tratamento com vancomicina

Objective: An augmented renal clearance has been described in some groups of critically ill patients, and it might induce sub-optimal concentrations of drugs eliminated by glomerular filtration, mainly antibiotics. Studies on its occurrence and determinants are lacking. Our goals were to determine the incidence and associated factors of augmented renal clearance and the efects on vancomycin concentrations and dosing in a series of intensive care unit patients. Methods: We prospectively studied 363 patients admitted during 1 year to a clinical-surgical intensive care unit. Patients with serum creatinine >1.3mg/dL were excluded. Creatinine clearance was calculated from a 24-hour urine collection. Patients were grouped according to the presence of augmented renal clearance (creatinine clearance >120mL/min/1.73m2), and possible risk factors were analyzed with bivariate and logistic regression analysis. In patients treated with vancomycin, dosage and plasma concentrations were registered. Results: Augmented renal clearance was present in 103 patients (28%); they were younger (48±15 versus 65±17 years, p>0.0001), had more frequent obstetric (16 versus 7%, p=0.0006) and trauma admissions (10 versus 3%, p=0.016) and fewer comorbidities. The only independent determinants for the development of augmented renal clearance were age (OR 0.95; p<0.0001; 95%CI 0.93-0.96) and absence of diabetes (OR 0.34; p=0.03; 95%CI 0.12-0.92). Twelve of the 46 patients who received vancomycin had augmented renal clearance and despite higher doses, had lower concentrations. Conclusions: In this cohort of critically ill patients, augmented renal clearance was a common finding. Age and absence of diabetes were the only independent determinants. Therefore, younger and previously healthy patients might require larger vancomycin dosing.Facultad de Ciencias Médica

Dissociation between sublingual and gut microcirculation in the response to a fluid challenge in postoperative patients with abdominal sepsis

Background: This study was performed to compare intestinal and sublingual microcirculation and their response to a fluid challenge. Methods: Twenty-two septic patients in the first postoperative day of an intestinal surgery, in which an ostomy had been constructed, were evaluated both before and 20 min after a challenge of 10 mL/kg of 6% hydroxyethylstarch 130/0.4. We measured systemic hemodynamics and sublingual and intestinal microcirculation. Correlations between variables were determined through the Pearson test. Results: Fluid administration increased the cardiac index (2.6 +/- 0.5 vs. 3.3 +/- 1.0 L/min/m(2), P <0.01) and mean arterial blood pressure (68 +/- 11 vs. 82 +/- 12 mm Hg, P <0.0001). The sublingual but not the intestinal red blood cell (RBC) velocity increased (912 +/- 270 vs. 1,064 +/- 200 mu m/s, P <0.002 and 679 +/- 379 vs. 747 +/- 419 mu m/s, P = 0.12, respectively). The sublingual and intestinal perfused vascular density (PVD) did not change significantly (15.2 +/- 2.9 vs. 16.1 +/- 1.2 mm/mm(2) and 12.3 +/- 6.7 vs. 13.0 +/- 6.7 mm/mm(2)). We found no correlation between the basal sublingual and intestinal RBC velocities or between their changes in response to the fluid challenge. The individual changes in sublingual RBC velocity correlated with those in cardiac index and basal RBC velocity. Individual changes in intestinal RBC velocity did not correlate with either the cardiac index modifications or the basal RBC velocity. The same pattern was observed with the sublingual and the intestinal PVDs. The sublingual RBC velocities and PVDs were similar between survivors and nonsurvivors. But the intestinal RBC velocities and PVDs were lower in nonsurvivors. Conclusions: In this series of postoperative septic patients, we found a dissociation between sublingual and intestinal microcirculation. The improvement in the sublingual microcirculation after fluid challenge was dependent on the basal state and the increase in cardiac output. In contrast, the intestinal microcirculation behaved as an isolated territor

Higher Fluid Balance Increases the Risk of Death From Sepsis: Results From a Large International Audit.

OBJECTIVES Excessive fluid therapy in patients with sepsis may be associated with risks that outweigh any benefit. We investigated the possible influence of early fluid balance on outcome in a large international database of ICU patients with sepsis. DESIGN Observational cohort study. SETTING Seven hundred and thirty ICUs in 84 countries. PATIENTS All adult patients admitted between May 8 and May 18, 2012, except admissions for routine postoperative surveillance. For this analysis, we included only the 1,808 patients with an admission diagnosis of sepsis. Patients were stratified according to quartiles of cumulative fluid balance 24 hours and 3 days after ICU admission. MEASUREMENTS AND MAIN RESULTS ICU and hospital mortality rates were 27.6% and 37.3%, respectively. The cumulative fluid balance increased from 1,217 mL (-90 to 2,783 mL) in the first 24 hours after ICU admission to 1,794 mL (-951 to 5,108 mL) on day 3 and decreased thereafter. The cumulative fluid intake was similar in survivors and nonsurvivors, but fluid balance was less positive in survivors because of higher fluid output in these patients. Fluid balances became negative after the third ICU day in survivors but remained positive in nonsurvivors. After adjustment for possible confounders in multivariable analysis, the 24-hour cumulative fluid balance was not associated with an increased hazard of 28-day in-hospital death. However, there was a stepwise increase in the hazard of death with higher quartiles of 3-day cumulative fluid balance in the whole population and after stratification according to the presence of septic shock. CONCLUSIONS In this large cohort of patients with sepsis, higher cumulative fluid balance at day 3 but not in the first 24 hours after ICU admission was independently associated with an increase in the hazard of death

Higher Fluid Balance Increases the Risk of Death From Sepsis : Results From a Large International Audit

OBJECTIVES: Excessive fluid therapy in patients with sepsis may be associated with risks that outweigh any benefit. We investigated the possible influence of early fluid balance on outcome in a large international database of ICU patients with sepsis. DESIGN: Observational cohort study. SETTING: Seven hundred and thirty ICUs in 84 countries. PATIENTS: All adult patients admitted between May 8 and May 18, 2012, except admissions for routine postoperative surveillance. For this analysis, we included only the 1,808 patients with an admission diagnosis of sepsis. Patients were stratified according to quartiles of cumulative fluid balance 24 hours and 3 days after ICU admission. MEASUREMENTS AND MAIN RESULTS: ICU and hospital mortality rates were 27.6% and 37.3%, respectively. The cumulative fluid balance increased from 1,217 mL (-90 to 2,783 mL) in the first 24 hours after ICU admission to 1,794 mL (-951 to 5,108 mL) on day 3 and decreased thereafter. The cumulative fluid intake was similar in survivors and nonsurvivors, but fluid balance was less positive in survivors because of higher fluid output in these patients. Fluid balances became negative after the third ICU day in survivors but remained positive in nonsurvivors. After adjustment for possible confounders in multivariable analysis, the 24-hour cumulative fluid balance was not associated with an increased hazard of 28-day in-hospital death. However, there was a stepwise increase in the hazard of death with higher quartiles of 3-day cumulative fluid balance in the whole population and after stratification according to the presence of septic shock. CONCLUSIONS: In this large cohort of patients with sepsis, higher cumulative fluid balance at day 3 but not in the first 24 hours after ICU admission was independently associated with an increase in the hazard of death

Incremento da depuração renal em pacientes gravemente enfermos: incidência, fatores associados e efeitos no tratamento com vancomicina

Objetivo: Foi descrito um incremento da depura&#231;&#227;o renal em alguns grupos de pacientes gravemente enfermos, o qual pode induzir &#224; elimina&#231;&#227;o de concentra&#231;&#245;es de f&#225;rmacos por filtra&#231;&#227;o glomerular aqu&#233;m do ideal, principalmente no caso de antibi&#243;ticos. Sua ocorr&#234;ncia e os fatores determinantes t&#234;m sido pouco estudados. Nossos objetivos foram determinar a incid&#234;ncia e os fatores associados ao incremento da depura&#231;&#227;o renal, bem como seus efeitos nas concentra&#231;&#245;es e na posologia de vancomicina em uma s&#233;rie de pacientes em unidade de terapia intensiva. M&#233;todos: Estudamos, de forma prospectiva, 363 pacientes admitidos durante 1 ano em uma unidade de terapia intensiva cl&#237;nico-cir&#250;rgica. Foram exclu&#237;dos pacientes que tivessem n&#237;vel de creatinina s&#233;rica >1,3mg/dL. A depura&#231;&#227;o de creatinina foi calculada a partir da coleta de urina de 24 horas. Os pacientes foram agrupados segundo a presen&#231;a de incremento da depura&#231;&#227;o renal (depura&#231;&#227;o de creatinina >120mL/min/1,73m2), e os poss&#237;veis fatores de risco foram analisados por meio de an&#225;lise bivariada e log&#237;stica. Em pacientes tratados com vancomicina, foram registradas a posologia e as concentra&#231;&#245;es plasm&#225;ticas. Resultados: O incremento da depura&#231;&#227;o renal esteve presente em 103 pacientes (28%), os quais eram mais jovens (48&#177;15 versus 65&#177;17 anos; p<0,0001), tinham mais frequentemente admiss&#245;es obst&#233;tricas (16 versus 7%; p=0,0006) e por trauma (10 versus 3%; p=0,016), e menos comorbidades. Os &#250;nicos determinantes independentes para o desenvolvimento de incremento da depura&#231;&#227;o renal foram idade (OR=0,95; IC95%=0,93-0,96; p<0,0001;) e aus&#234;ncia de diabetes (OR 0,34; IC95% 0,12-0,92; p=0,03). Doze dos 46 pacientes que receberam vancomicina tinham incremento da depura&#231;&#227;o renal e, apesar das doses elevadas, tinham concentra&#231;&#245;es plasm&#225;ticas de vancomicina mais baixas. Conclus&#245;es: Nessa coorte de pacientes gravemente enfermos, foi frequente o achado de incremento da depura&#231;&#227;o renal. Idade e aus&#234;ncia de diabetes foram os &#250;nicos determinantes independentes. Assim, pacientes jovens e previamente saud&#225;veis podem necessitar de doses mais elevadas de vancomicina

Higher Fluid Balance Increases the Risk of Death From Sepsis: Results From a Large International Audit.

OBJECTIVES Excessive fluid therapy in patients with sepsis may be associated with risks that outweigh any benefit. We investigated the possible influence of early fluid balance on outcome in a large international database of ICU patients with sepsis. DESIGN Observational cohort study. SETTING Seven hundred and thirty ICUs in 84 countries. PATIENTS All adult patients admitted between May 8 and May 18, 2012, except admissions for routine postoperative surveillance. For this analysis, we included only the 1,808 patients with an admission diagnosis of sepsis. Patients were stratified according to quartiles of cumulative fluid balance 24 hours and 3 days after ICU admission. MEASUREMENTS AND MAIN RESULTS ICU and hospital mortality rates were 27.6% and 37.3%, respectively. The cumulative fluid balance increased from 1,217 mL (-90 to 2,783 mL) in the first 24 hours after ICU admission to 1,794 mL (-951 to 5,108 mL) on day 3 and decreased thereafter. The cumulative fluid intake was similar in survivors and nonsurvivors, but fluid balance was less positive in survivors because of higher fluid output in these patients. Fluid balances became negative after the third ICU day in survivors but remained positive in nonsurvivors. After adjustment for possible confounders in multivariable analysis, the 24-hour cumulative fluid balance was not associated with an increased hazard of 28-day in-hospital death. However, there was a stepwise increase in the hazard of death with higher quartiles of 3-day cumulative fluid balance in the whole population and after stratification according to the presence of septic shock. CONCLUSIONS In this large cohort of patients with sepsis, higher cumulative fluid balance at day 3 but not in the first 24 hours after ICU admission was independently associated with an increase in the hazard of death

Regulation of human neutrophil IL-1β secretion induced by Escherichia coli O157:H7 responsible for hemolytic uremic syndrome.

Shiga-toxin producing Escherichia coli (STEC) infections can cause from bloody diarrhea to Hemolytic Uremic Syndrome. The STEC intestinal infection triggers an inflammatory response that can facilitate the development of a systemic disease. We report here that neutrophils might contribute to this inflammatory response by secreting Interleukin 1 beta (IL-1β). STEC stimulated neutrophils to release elevated levels of IL-1β through a mechanism that involved the activation of caspase-1 driven by the NLRP3-inflammasome and neutrophil serine proteases (NSPs). Noteworthy, IL-1β secretion was higher at lower multiplicities of infection. This secretory profile modulated by the bacteria:neutrophil ratio, was the consequence of a regulatory mechanism that reduced IL-1β secretion the higher were the levels of activation of both caspase-1 and NSPs, and the production of NADPH oxidase-dependent reactive oxygen species. Finally, we also found that inhibition of NSPs significantly reduced STEC-triggered IL-1β secretion without modulating the ability of neutrophils to kill the bacteria, suggesting NSPs might represent pharmacological targets to be evaluated to limit the STEC-induced intestinal inflammation