Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: A prospective study

Introduction: Our goal was to assess the effects of titration of a norepinephrine infusion to increasing levels of mean arterial pressure (MAP) on sublingual microcirculation. Methods: Twenty septic shock patients were prospectively studied in two teaching intensive care units. The patients were mechanically ventilated and required norepinephrine to maintain a mean arterial pressure (MAP) of 65 mmHg. We measured systemic hemodynamics, oxygen transport and consumption (DO2 and VO2), lactate, albumin-corrected anion gap, and gastric intramucosal-arterial PCO2 difference (ΔPCO2). Sublingual microcirculation was evaluated by sidestream darkfield (SDF) imaging. After basal measurements at a MAP of 65 mmHg, norepinephrine was titrated to reach a MAP of 75 mmHg, and then to 85 mmHg. Data were analyzed using repeated measurements ANOVA and Dunnett test. Linear trends between the different variables and increasing levels of MAP were calculated. Results: Increasing doses of norepinephrine reached the target values of MAP. The cardiac index, pulmonary pressures, systemic vascular resistance, and left and right ventricular stroke work indexes increased as norepinephrine infusion was augmented. Heart rate, DO2 and VO2, lactate, albumin-corrected anion gap, and ΔPCO2 remained unchanged. There were no changes in sublingual capillary microvascular flow index (2.1 ± 0.7, 2.2 ± 0.7, 2.0 ± 0.8) and the percent of perfused capillaries (72 ± 26, 71 ± 27, 67 ± 32%) for MAP values of 65, 75, and 85 mmHg, respectively. There was, however, a trend to decreased capillary perfused density (18 ± 10,17 ± 10,14 ± 2 vessels/mm2, respectively, ANOVA P = 0.09, linear trend P = 0.045). In addition, the changes of perfused capillary density at increasing MAP were inversely correlated with the basal perfused capillary density (R2 = 0.95, P < 0.0001). Conclusions: Patients with septic shock showed severe sublingual microcirculatory alterations that failed to improve with the increases in MAP with norepinephrine. Nevertheless, there was a considerable interindividual variation. Our results suggest that the increase in MAP above 65 mmHg is not an adequate approach to improve microcirculatory perfusion and might be harmful in some patients.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

Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: A prospective study

Introduction: Our goal was to assess the effects of titration of a norepinephrine infusion to increasing levels of mean arterial pressure (MAP) on sublingual microcirculation. Methods: Twenty septic shock patients were prospectively studied in two teaching intensive care units. The patients were mechanically ventilated and required norepinephrine to maintain a mean arterial pressure (MAP) of 65 mmHg. We measured systemic hemodynamics, oxygen transport and consumption (DO2 and VO2), lactate, albumin-corrected anion gap, and gastric intramucosal-arterial PCO2 difference (ΔPCO2). Sublingual microcirculation was evaluated by sidestream darkfield (SDF) imaging. After basal measurements at a MAP of 65 mmHg, norepinephrine was titrated to reach a MAP of 75 mmHg, and then to 85 mmHg. Data were analyzed using repeated measurements ANOVA and Dunnett test. Linear trends between the different variables and increasing levels of MAP were calculated. Results: Increasing doses of norepinephrine reached the target values of MAP. The cardiac index, pulmonary pressures, systemic vascular resistance, and left and right ventricular stroke work indexes increased as norepinephrine infusion was augmented. Heart rate, DO2 and VO2, lactate, albumin-corrected anion gap, and ΔPCO2 remained unchanged. There were no changes in sublingual capillary microvascular flow index (2.1 ± 0.7, 2.2 ± 0.7, 2.0 ± 0.8) and the percent of perfused capillaries (72 ± 26, 71 ± 27, 67 ± 32%) for MAP values of 65, 75, and 85 mmHg, respectively. There was, however, a trend to decreased capillary perfused density (18 ± 10,17 ± 10,14 ± 2 vessels/mm2, respectively, ANOVA P = 0.09, linear trend P = 0.045). In addition, the changes of perfused capillary density at increasing MAP were inversely correlated with the basal perfused capillary density (R2 = 0.95, P < 0.0001). Conclusions: Patients with septic shock showed severe sublingual microcirculatory alterations that failed to improve with the increases in MAP with norepinephrine. Nevertheless, there was a considerable interindividual variation. Our results suggest that the increase in MAP above 65 mmHg is not an adequate approach to improve microcirculatory perfusion and might be harmful in some patients.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

Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study

Introduction Our goal was to assess the effects of titration of a norepinephrine infusion to increasing levels of mean arterial pressure (MAP) on sublingual microcirculation. Methods Twenty septic shock patients were prospectively studied in two teaching intensive care units. The patients were mechanically ventilated and required norepinephrine to maintain a mean arterial pressure (MAP) of 65 mmHg. We measured systemic hemodynamics, oxygen transport and consumption (DO2 and VO2), lactate, albumin-corrected anion gap, and gastric intramucosal-arterial PCO2 difference (Delta PCO2). Sublingual microcirculation was evaluated by sidestream darkfield (SDF) imaging. After basal measurements at a MAP of 65 mmHg, norepinephrine was titrated to reach a MAP of 75 mmHg, and then to 85 mmHg. Data were analyzed using repeated measurements ANOVA and Dunnett test. Linear trends between the different variables and increasing levels of MAP were calculated. Results Increasing doses of norepinephrine reached the target values of MAP. The cardiac index, pulmonary pressures, systemic vascular resistance, and left and right ventricular stroke work indexes increased as norepinephrine infusion was augmented. Heart rate, DO2 and VO2, lactate, albumin-corrected anion gap, and Delta PCO2 remained unchanged. There were no changes in sublingual capillary microvascular flow index (2.1 +/- 0.7, 2.2 +/- 0.7, 2.0 +/- 0.8) and the percent of perfused capillaries (72 +/- 26, 71 +/- 27, 67 +/- 32%) for MAP values of 65, 75, and 85 mmHg, respectively. There was, however, a trend to decreased capillary perfused density (18 +/- 10,17 +/- 10,14 +/- 2 vessels/mm(2), respectively, ANOVA P = 0.09, linear trend P = 0.045). In addition, the changes of perfused capillary density at increasing MAP were inversely correlated with the basal perfused capillary density (R-2 = 0.95, P < 0.0001). Conclusions Patients with septic shock showed severe sublingual microcirculatory alterations that failed to improve with the increases in MAP with norepinephrine. Nevertheless, there was a considerable interindividual variation. Our results suggest that the increase in MAP above 65 mmHg is not an adequate approach to improve microcirculatory perfusion and might be harmful in some patient

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

Predictability of adverse outcomes in hypertensive disorders of pregnancy: a multicenter prospective cohort study

Objectives To explore variables associated with adverse maternal/fetal/neonatal outcomes among pregnant/postpartum patients admitted to ICU for hypertensive disorders of pregnancy (HDP). Methods Multicenter, prospective, national cohort study. Results Variables independently associated with maternal/fetal/neonatal mortality among 172 patients were as follows: Acute Physiology and Chronic Health Evaluation-II (APACHE-II)(OR1.20[1.06–1.35]), gestational age (OR0.698[0.59–0.82]) and aspartate aminotransferase (AST)(OR1.004[1.001–1.006]). Positive likelihood ratio for headache, epigastric pain, and visual disturbances to predict composite adverse outcomes were 1.23(1.16–1.30), 0.76(0.59–1.02), and 1.1(0.98–1.2), respectively. Conclusions Maternal/fetal mortality due to HDP was independently associated with severity of illness on admission, gestational age, and elevated AST. Accuracy of clinical symptoms to predict composite adverse outcomes was low