Incoherence between Systemic Hemodynamic and Microcirculatory Response to Fluid Challenge in Critically Ill Patients.

BACKGROUND: The aim of the study was to assess the coherence between systemic hemodynamic and microcirculatory response to a fluid challenge (FC) in critically ill patients. METHODS: We prospectively collected data in patients requiring a FC whilst cardiac index (CI) and microcirculation were monitored. The sublingual microcirculation was assessed using the incident dark field (IDF) CytoCam device (Braedius Medical, Huizen, The Netherlands). The proportion of small perfused vessels (PPV) was calculated. Fluid responders were defined by at least a 10% increase in CI during FC. Responders according to changes in microcirculation were defined by at least 10% increase in PPV at the end of FC. Cohen's kappa coefficient was measured to assess the agreement to categorize patients as "responders" to FC according to CI and PPV. RESULTS: A total of 41 FC were performed in 38 patients, after a median time of 1 (0-1) days after ICU admission. Most of the fluid challenges (39/41, 95%) were performed using crystalloids and the median total amount of fluid was 500 (500-500) mL. The main reasons for fluid challenge were oliguria (n = 22) and hypotension (n = 10). After FC, CI significantly increased in 24 (58%) cases; a total of 19 (46%) FCs resulted in an increase in PPV. Both CI and PPV increased in 13 responders and neither in 11; the coefficient of agreement was only 0.21. We found no correlation between absolute changes in CI and PPV after fluid challenge. CONCLUSIONS: The results of this heterogenous population of critically ill patients suggest incoherence in fluid responsiveness between systemic and microvascular hemodynamics; larger cohort prospective studies with adequate a priori sample size calculations are needed to confirm these findings.

[Pulse pressure variation guided fluid therapy during kidney transplantation: a randomized controlled trial]. / Reposição de volume orientada pela variação da pressão de pulso durante transplante renal: estudo randomizado controlado.

PURPOSE: Kidney transplantation is the gold-standard treatment for end stage renal disease. Although different hemodynamic variables, like central venous pressure and mean arterial pressure, have been used to guide volume replacement during surgery, the best strategy still ought to be determined. Respiratory arterial Pulse Pressure Variation (PPV) is recognized to be a good predictor of fluid responsiveness for perioperative hemodynamic optimization in operating room settings. The aim of this study was to investigate whether a PPV-guided fluid management strategy is better than a liberal fluid strategy during kidney transplantation surgeries. Identification of differences in urine output in the first postoperative hour was the main objective of this study. METHODS: We conducted a prospective, single blind, randomized controlled trial. We enrolled 40 patients who underwent kidney transplantation from deceased donors. Patients randomized in the PPV Group received fluids whenever PPV was higher than 12%, patients in the Free Fluid Group received fluids following our institutional standard care protocol for kidney transplantations (10mL.kg-1.h-1). RESULTS: Urinary output was similar at every time-point between the two groups, urea was statistically different from the third postoperative day with a peak at the fourth postoperative day and creatinine showed a similar trend, being statistically different from the second postoperative day. Urea, creatinine and urine output were not different at the hospital discharge. CONCLUSION: PPV-guided fluid therapy during kidney transplantation significantly improves urea and creatinine levels in the first week after kidney transplantation surgery.

Pulse pressure variation guided fluid therapy during kidney transplantation: a randomized controlled trial / Reposição de volume orientada pela variação da pressão de pulso durante transplante renal: estudo randomizado controlado

Abstract Purpose: Kidney transplantation is the gold-standard treatment for end stage renal disease. Although different hemodynamic variables, like central venous pressure and mean arterial pressure, have been used to guide volume replacement during surgery, the best strategy still ought to be determined. Respiratory arterial Pulse Pressure Variation (PPV) is recognized to be a good predictor of fluid responsiveness for perioperative hemodynamic optimization in operating room settings. The aim of this study was to investigate whether a PPV guided fluid management strategy is better than a liberal fluid strategy during kidney transplantation surgeries. Identification of differences in urine output in the first postoperative hour was the main objective of this study. Methods: We conducted a prospective, single blind, randomized controlled trial. We enrolled 40 patients who underwent kidney transplantation from deceased donors. Patients randomized in the "PPV" group received fluids whenever PPV was higher than 12%, patients in the "free fluid" group received fluids following our institutional standard care protocol for kidney transplantations (10 mL.kg-1. h-1). Results: Urinary output was similar at every time-point between the two groups, urea was statistically different from the third postoperative day with a peak at the fourth postoperative day and creatinine showed a similar trend, being statistically different from the second postoperative day. Urea, creatinine and urine output were not different at the hospital discharge. Conclusion: PPV guided fluid therapy during kidney transplantation significantly improves urea and creatinine levels in the first week after kidney transplantation surgery.

Resumo Objetivo: Transplante renal é o tratamento padrão-ouro na doença renal em estágio terminal. Embora diferentes variáveis hemodinâmicas, tais como pressão venosa central e pressão arterial média, têm sido usadas para orientar a estratégia de reposição volêmica durante a cirurgia, a melhor estratégia ainda não foi determinada. A Variação da Pressão de Pulso (VPP) durante o ciclo respiratório é reconhecida como um bom preditor da resposta à infusão de volume para otimização hemodinâmica perioperatória no centro cirúrgico. O objetivo do estudo foi estudar se a estratégia de reposição de volume orientada por VPP é melhor do que a estratégia liberal de reposição de volume durante cirurgia de transplante renal. O principal objetivo do estudo foi identificar diferença no débito urinário na primeira hora do pós-operatório. Método: Realizamos estudo prospectivo, unicego, randomizado, controlado. Incluímos 40 pacientes submetidos a transplante renal de doador cadáver. Pacientes randomizados para o Grupo VPP receberam volume quando a VPP estava acima de 12%, e os pacientes no Grupo Reposição Liberal receberam volume de acordo com o nosso protocolo institucional padrão de assistência para transplante renal (10 mL.kg-1.h-1). Resultados: O débito urinário foi semelhante em todos os tempos nos dois grupos, a ureia foi estatisticamente diferente a partir do terceiro dia do pós-operatório com pico no quarto dia do pós-operatório e a creatinina apresentou tendência semelhante, tornando-se estatisticamente diferente a partir do segundo dia do pós-operatório. Ureia, creatinina e débito urinário não estavam diferentes na alta hospitalar. Conclusões: A terapia orientada por VPP durante transplante renal melhorou de forma significativa os níveis de ureia e creatinina na primeira semana pós-transplante renal.

Comparison of estimation of cardiac output using an uncalibrated pulse contour method and echocardiography during veno-venous extracorporeal membrane oxygenation.

INTRODUCTION: During veno-venous extracorporeal membrane oxygenation, cardiac output monitoring is essential to assess tissue oxygen delivery. Adequate arterial oxygenation depends on the ratio between the extracorporeal pump blood flow and the cardiac output. The aim of this study was to compare estimates of cardiac output and blood flow/cardiac output ratios made using an uncalibrated pulse contour method with those made using echocardiography in patients treated with veno-venous extracorporeal membrane oxygenation. METHODS: Cardiac output was estimated simultaneously using a pulse contour method (MostCareUp; Vygon, Encouen, France) and echocardiography in 17 hemodynamically stable patients treated with veno-venous extracorporeal membrane oxygenation. Comparisons were made using Bland-Altman and linear regression analysis. RESULTS: There were significant correlations between cardiac output estimated using pulse contour method and echocardiography and between blood flow/cardiac output estimated using pulse contour method and blood flow/cardiac output estimated using echocardiography (r = 0.84, p < 0.001 and r = 0.87, p < 0.001, respectively). Bland-Altman analysis showed a good agreement (bias -0.20 ± 0.50 L/min) and a low percentage of error (25%) for the cardiac output values estimated by the two methods. The bias between the blood flow/cardiac output ratios obtained with the two methods was 5.19% ± 12.3% (percentage of error = 28.1%). CONCLUSIONS: The pulse contour method is a valuable alternative to echocardiography for the assessment of cardiac output and the blood flow/cardiac output ratio in patients treated with veno-venous extracorporeal membrane oxygenation.

Relationship between Microcirculatory Perfusion and Arterial Elastance: A Pilot Study.

BACKGROUND: Arterial elastance (Ea) represents the total afterload imposed on the left ventricle, and it is largely influenced by systemic vascular resistance (SVR). Although one can expect that Ea is influenced by peripheral endothelial function, no data are available to support it in patients. The aim of this study was to investigate the relationship between Ea, SVR, and microvascular perfusion in critically ill patients undergoing the fluid challenge (FC). METHODS: A prospective study in patients receiving a fluid challenge. A pulse wave analysis system (MostCare, Vygon, France) was used to estimate Ea and an incident dark field (IDF) handheld device (Braedius Medical BV, The Netherlands) to evaluate the sublingual microcirculation. Microvascular perfusion was assessed using the proportion of small-perfused vessels (PPV). Relative changes in each variable were calculated before and after FC; fluid responsiveness was defined as an increase in the cardiac index by at least 10% from baseline. RESULTS: We studied 20 patients requiring a fluid challenge (n=10 for hypotension; n=5 for oliguria; n=3 for lactate values greater than 2 mmol/l; n=2 for tachycardia), including 12 fluid responders. There was a strong correlation between Ea and SVR (r 2 = 0.75; p < 0.001) and only a weak correlation between Ea and PPV at baseline (r 2 = 0.22; p=0.04). Ea decreased from 1.4 [1.2-1.6] to 1.2 [1.1-1.4] mmHg/mL (p=0.01), SVR from 1207 [1006-1373] to 1073 [997-1202] dyn ∗ s/cm5 (p=0.06), and PPV from 56 [51-64] % to 59 [47-73] % (p=0.25) after fluid challenge. Changes in Ea were significantly correlated with changes in SVR, but not with changes in PPV. CONCLUSIONS: The correlation between Ea and indexes of microvascular perfusion in the sublingual region is weak. The impact of microcirculatory perfusion on the arterial load is probably limited.

Red Cell Distribution Width After Subarachnoid Hemorrhage.

BACKGROUND: High red cell distribution width (RDW) values have been associated with increased hospital mortality in critically ill patients, but few data are available for subarachnoid hemorrhage (SAH). METHODS: We analyzed an institutional database of adult (>18 y) patients admitted to the Department of Intensive Care after nontraumatic SAH between January 2011 and May 2016. RDW (normal value, 10.9% to 13.4%) was obtained daily from admission for a maximum of 7 days, from routine blood analysis. We recorded the occurrence of delayed cerebral ischemia (DCI), and neurological outcome (assessed using the Glasgow Outcome Scale [GOS]) at 3 months. RESULTS: A total of 270 patients were included (median age 54 y-121/270 male [45%]), of whom 96 (36%) developed DCI and 109 (40%) had an unfavorable neurological outcome (GOS, 1 to 3). The median RDW on admission was 13.8 [13.3 to 14.5]% and the highest value during the intensive care unit (ICU) stay 14.2 [13.6 to 14.8]%. The RDW was high (>13.4%) in 177 patients (66%) on admission and in 217 (80%) at any time during the ICU stay. Patients with a high RDW on admission were more likely to have an unfavorable neurological outcome. In multivariable regression analysis, older age, a high WFNS grade on admission, presence of DCI or intracranial hypertension, previous neurological disease, vasopressor therapy and a high RDW (OR, 1.1618 [95% CI, 1.213-2.158]; P=0.001) during the ICU stay were independent predictors of unfavorable neurological outcome. CONCLUSIONS: High RDW values were more likely to result in an unfavorable outcome after SAH. This information could help in the stratification of SAH patients already on ICU admission.

No relationship between red blood cell distribution width and microcirculatory alterations in septic patients.

BACKGROUND: Increased red cell distribution width (RDW), a quantitative measure of erythrocyte size variability, has been associated with increased mortality in critically ill patients. METHODS: In this post-hoc analysis of prospectively collected data, we studied 122 septic patients with and without shock who had undergone sublingual microcirculatory assessment using Sidestream Dark Field (SDF) videomicroscopy. Patient demographics, comorbidities, the Acute Physiology and Chronic Health Evaluation (APACHE) II score on admission and the Sequential Organ Failure Assessment (SOFA) score on the day of the microcirculatory assessment were collected. The RDW was retrospectively collected on the day of the microcirculatory evaluation from the routine daily blood count analysis. RESULTS: Median patient age was 68[55-77] years, and median APACHE II and SOFA scores were 22[17-28] and 10[8-12], respectively; ICU mortality was 43%. On the day of the microcirculatory analysis, the median RDW was 13.8[12.8-15.5]% and was elevated (>13.4%) in 74 (61%) patients. There was no correlation between RDW and microcirculatory parameters (functional capillary density, r2 = 0.12; proportion of small perfused vessels, r2 = 0.17; mean flow index, r2 = 0.14). RDW was not related to disease severity, the presence of shock or survival. CONCLUSIONS: RDW is not associated with microcirculatory alterations or prognosis in septic patients.

Individualized antibiotic strategies.

PURPOSE OF REVIEW: Infections are common complications in critically ill patients and are frequently treated with antibiotics. Unfortunately, delivery of optimal therapy is complicated because efficacy of antimicrobials is influenced by the timing of treatment initiation, the use of combination therapy, and the optimization of drug dosing. RECENT FINDINGS: Early diagnosis of infection is mandatory to provide a rapid and appropriate antibiotic therapy. The presence of less susceptible strains, in particular for hospital-acquired infections, or patients with severe disease, such as the presence of septic shock, may need combination antibiotic therapy. Antibiotic pharmacokinetics, notably volume of distribution and total body clearance, are significantly altered in these critically ill patients and can influence the attainment of adequate circulating levels when standard dosage regimens are administered. Higher dosing should be considered in such patients, although in case of renal impairment and reduced clearance, drug accumulation could also result in some side-effects. Nebulized antibiotics may provide a better clinical response than systemic antibiotics in ventilator-associated pneumonia because of multidrug-resistant pathogens. SUMMARY: The optimal use of antibiotics in the management of severe infections is an important challenge for ICU physicians. Antimicrobial therapy needs to be individualized according to specific patient characteristics, infecting organisms, and susceptibility patterns.