Antoine Dewitte

Doppler resistive index to reflect regulation of renal vascular tone during sepsis and acute kidney injury

IntroductionRenal resistive index (RI), determined by Doppler ultrasonography, directly reveals and quantifies modifications in renal vascular resistance. The aim of this study was to evaluate if mean arterial pressure (MAP) is determinant of renal RI in septic, critically ill patients suffering or not from acute kidney injury (AKI).MethodsThis prospective observational study included 96 patients. AKI was defined according to RIFLE criteria and transient or persistent AKI according to renal recovery within 3 days.ResultsMedian renal RIs were 0.72 (0.68-0.75) in patients without AKI and 0.76 (0.72-0.80) in patients with AKI (P=0.001). RIs were 0.75 (0.72-0.79) in transient AKI and 0.77 (0.70-0.80) in persistent AKI (P=0.84). RI did not differ in patients given norepinephrine infusion and was not correlated with norepinephrine dose. RI was correlated with MAP (ρ= -0.47; P=0.002), PaO2/FiO2 ratio (ρ= -0.33; P=0.04) and age (ρ=0.35; P=0.015) only in patients without AKI.ConclusionsA poor correlation between renal RI and MAP, age, or PaO2/FiO2 ratio was found in septic and critically ill patients without AKI compared to patients with AKI. These findings suggest that determinants of RI are multiple. Renal circulatory response to sepsis estimated by Doppler ultrasonography cannot reliably be predicted simply from changes in systemic hemodynamics. As many factors influence its value, the interest in a single RI measurement at ICU admission to determine optimal MAP remains uncertain.

Precision of noninvasive hemoglobin-level measurement by pulse co-oximetry in patients admitted to intensive care units for severe gastrointestinal bleeds.

Objectives:Measurement of total hemoglobin, based on pulse co-oximetry, is a continuous and noninvasive method that has been principally evaluated in healthy volunteers subjected to hemodilution. We tested the hypothesis that its accuracy could adversely affect patients presenting with severe hemorrhage, which is traditionally associated with increased microvascular tone. Design:Observational study. Setting:Twelve-bed mixed medico-surgical intensive care unit. Patients:Thirty-three patients admitted to our critical care unit for gastrointestinal bleeds were included. Interventions:A spectrophotometric sensor was positioned on the patient’s fingertip and connected to a pulse co-oximeter. During the first 24 hrs following admission, venous hemoglobin level was determined at the laboratory every 8 hrs and was compared with hemoglobin levels displayed on the pulse co-oximeter measurements screen and/or measured from capillary blood using a portable photometer. Measurements and Main Results:The primary end point was the percentage of inaccurate measurements, which were defined as >15% difference compared with reference values or their unavailability for any technical reason. Twenty-five (19%) measurements of pulse co-oximeter measurements were unavailable from the screen. Pulse co-oximeter measurements and capillary hemoglobin levels were significantly correlated to venous hemoglobin level. For venous hemoglobin level compared with pulse co-oximeter measurements (n = 105), and for venous hemoglobin level compared with capillary hemoglobin levels (n = 111), the biases were, respectively, 1.0 ± 1.9 g dL−1 and 0.4 ± 1.0 g dL−1 (p < .05). The proportion of inaccurate measurements was significantly higher for pulse co-oximeter measurements (56% vs. 15%, p < .05). Although the use of norepinephrine did not affect concordance parameters, unavailability of measurements was frequently observed (42% vs. 15%, p < .05). Conclusions:Determination of pulse co-oximetry-based hemoglobin in patients presenting with severe gastrointestinal bleeds can be inaccurate, which renders its use to guide transfusion decisions potentially hazardous. The unavailability of measurements, especially during vasopressor infusion, represents another serious limitation for hemorrhagic patients.

Doppler-based renal resistive index for prediction of renal dysfunction reversibility: A systematic review and meta-analysis ☆

BACKGROUND AND OBJECTIVES Doppler-based renal resistive index (RI) might help in distinguishing transient from persistent acute kidney injury (AKI). The main objective of these systematic review and meta-analysis was to investigate the diagnostic performance of RI in predicting short-term reversibility of AKI. STUDY DESIGN A systematic review of the literature was performed. Relevant studies were identified in Pubmed and Cochrane databases covering the years 1985 to 2013 and reviewed independently by 3 authors. Renal transplant recipients were excluded from this analysis. The summary estimates were computed using a random-effects model based on the DerSimonian and Lair meta-analytic method. RESULTS Among the 154 unique articles identified, 9 studies were included. Of the 176 patients in these studies with elevated RI or pulsatility index, 146 (83%) had a persistent AKI vs 44 (16%) of the 273 patients with normal values. Elevated RI or pulsatility index was associated with an increased risk of persistent AKI (odds ratio, 29.85; 95% confidence interval [CI], 8.73-102.16; P < .00001) with significant heterogeneity (I(2) = 75.0%, P < .0001). The pooled sensitivity and specificity were 0.83 (95% CI, 0.77-0.88) and 0.84 (95% CI, 0.79-0.88). The summary positive and negative likelihood ratios were 4.9 (95% CI, 2.44-9.87) and 0.21 (95% CI, 0.11-0.41). CONCLUSION These results suggest that an elevated RI may be a predictor of persistent AKI in critically ill patients. Further studies are warranted, however, to clarify the exact test performance given the marked heterogeneity among the included studies.

Neuro-ventilatory efficiency during weaning from mechanical ventilation using neurally adjusted ventilatory assist

BACKGROUND Neuro-ventilatory efficiency (NVE), defined as the tidal volume to electrical diaphragm-activity ratio (VT/EAdi) at the beginning and end of the weaning process after acute hypoxaemic respiratory failure, may provide valuable information about patient recovery. METHODS This observational study included 12 patients breathing with neurally adjusted ventilatory assist (NAVA). When a spontaneous breathing trial (SBT) with pressure support of 7 cm H2O and PEEP was unsuccessful, NAVA was used and the level was adjusted to obtain an EAdi of ∼60% of maximal EAdi during SBT. VT and EAdi were recorded continuously. We compared changes in NVE between NAVA and SBT at the first failed and first successful SBT. RESULTS When patients were switched from NAVA to SBT, NVE was significantly reduced during both unsuccessful and successful SBT (-56 and -38%, respectively); however, this reduction was significantly lower when SBT was successful (P=0.01). Between the first and last day of weaning, we observed that NVE decreased with NAVA [40.6 (27.7-89.5) vs 28.8 (18.6-46.7); P=0.002] with a significant decrease in NAVA level, whereas it remained unchanged during SBT [15.4 (10.7-39.1) vs 19.5 (11.6-29.6); P=0.50] with significant increases in both EAdi and VT and no difference in respiratory rhythm. CONCLUSIONS These results suggest that in patients after respiratory failure and prolonged mechanical ventilation, changes in VT and NVE, between SBTs are indicative of patient recovery. Larger clinical trials are needed to clarify whether changes in NVE reliably predict weaning in patients ventilated with NAVA.

Accuracy of determining hemoglobin level using occlusion spectroscopy in patients with severe gastrointestinal bleeding.

Background:In patients presenting with severe hemorrhage, the authors conducted an equivalence trial that compared noninvasive occlusion spectroscopy and the capillary blood method to determine hemoglobin level. Methods:This prospective observational study included patients admitted to their intensive care unit for gastrointestinal bleeding. A ring-shaped sensor, connected to a NBM-200MP (OrSense®, Nes Ziona, Israel), was fitted onto the patient’s thumb to intermittently measure hemoglobin (SotHb). During the first 24 h after admission, venous hemoglobin level, considered as the reference method, was determined at the laboratory every 8 h and was compared to SotHb and the capillary blood method. The primary endpoint was the proportion of inaccurate measurements, defined as greater than 15% difference compared with reference values or their unavailability for any technical reason. Results:The study was scheduled to include 68 patients but was stopped prematurely after an interim analysis of 34 patients. The proportion of inaccuracies revealed that SotHb could not be considered equivalent to the capillary blood method (47% [95% CI, 43–51] and 24% [95% CI, 20–28]). Considering venous hemoglobin level as a reference method, the mean biases for SotHb (n = 133) and the capillary blood method (n = 135) were, respectively, −0.4 ± 2.0 and 0.8 ± 1.2 g/dl (P < 0.05). SotHb was associated with an increased incidence of failed transfusion. The inaccuracy of SotHb tended to be increased in patients receiving vasopressor agents. Conclusions:Noninvasive determination of hemoglobin level based on occlusion spectroscopy lacks accuracy in patients presenting with severe gastrointestinal bleeding and cannot be considered equivalent to the capillary-based method. This inaccuracy seems to be moderately influenced by the infusion of vasopressor agents.

Fractional excretion of urea as a diagnostic index in acute kidney injury in intensive care patients

PURPOSE Acute kidney injury (AKI) is a dynamic process that evolves from an early reversible condition to an established disease. Value of urine indices in the event of AKI is uncertain in critically ill patients. The aim of this study was to evaluate the performance of fractional excretion of urea (FeU) for differentiating persistent from transient AKI in patients admitted to the intensive care unit. METHODS This was an observational study. Forty-seven patients with AKI according to the RIFLE classification were included. Transient AKI was defined as AKI resolved within 3 days after inclusion. Persistent AKI was defined as persistent serum creatinine elevation or oliguria. RESULTS Fractional excretion of urea was lower in case of transient, 33% (25-39), than persistent AKI, 47% (36-61) (P = .001). Areas under the receiver operating characteristic curve for FeU in case of transient AKI were better than those for other urinary indexes, 0.78 (95% confidence interval, 0.63-0.92). Optimal cutoff point according to the receiver operating characteristic curve was 40%. In patients treated with diuretics, FeU was the only predictive index of transient AKI. Fractional excretion of urea gradually increased from days 1 to 7 in transient AKI, whereas plasma creatinine decreased. CONCLUSIONS Fractional excretion of urea less than 40% was found to be a sensitive and specific index in differentiating transient from persistent AKI in intensive care unit patients especially if diuretics had been administered.

New frontiers for platelet CD154

The role of platelets extends beyond hemostasis. The pivotal role of platelets in inflammation has shed new light on the natural history of conditions associated with acute or chronic inflammation. Beyond the preservation of vascular integrity, platelets are essential to tissue homeostasis and platelet-derived products are already used in the clinics. Unanticipated was the role of platelets in the adaptative immune response, allowing a renewed conceptual approach of auto-immune diseases. Platelets are also important players in cancer growth and dissemination. Platelets fulfill most of their functions through the expression of still incompletely characterized membrane-bound or soluble mediators. Among them, CD154 holds a peculiar position, as platelets represent a major source of CD154 and as CD154 contributes to most of these new platelet attributes. Here, we provide an overview of some of the new frontiers that the study of platelet CD154 is opening, in inflammation, tissue homeostasis, immune response, hematopoiesis and cancer.

Effect of flumazenil on diaphragm electrical activation during weaning from mechanical ventilation after acute respiratory distress syndrome

BACKGROUND Diaphragm electrical activation (EAdi) and the ratio of tidal volume to EAdi (VT/EAdi) may provide clinical information on neuroventilatory efficiency (NVE) in patients being weaned from mechanical ventilation. We tested the hypothesis that residual sedation could interfere with respiratory recovery, by assessing the effects of flumazenil on EAdi and VT/EAdi ratio. METHODS This observational study included 13 patients breathing with pressure-support ventilation (PSV) after a long period of controlled mechanical ventilation (i.e. >4 days) plus midazolam-based sedation for acute respiratory distress syndrome. EAdi and respiratory patterns were compared before and after a bolus of flumazenil, which was given because neurological status needed to be evaluated. RESULTS Flumazenil induced a significant increase in EAdi [+71 (41-123)%, P=0.0002] and VT [+17 (8-32)%, P=0.0005], resulting in significantly decreased NVE [-34 (15-43)%]. The increased VT was significantly correlated with the increased EAdi (ρ=0.70, P=0.009). CONCLUSIONS During weaning from mechanical ventilation, the diaphragmatic contribution to the breathing process may be reduced by residual midazolam-induced ventilatory depression. The increased EAdi with reversal of residual sedation was associated with a proportional increase in VT. These findings should be considered by the attending physician when interpreting daily EAdi and VT changes during weaning from mechanical ventilation.

CD154 Induces Matrix Metalloproteinase‐9 Secretion in Human Podocytes

Matrix remodeling is a key feature of glomerulosclerosis secondary to diabetes or hypertension. Podocytes contribute to glomerular basement membrane (GBM) turnover by producing matrix components and matrix remodelling enzymes, including matrix metalloproteinases (MMPs). The CD40/CD154 signaling pathway modulates matrix remodeling through the synthesis of MMPs and tissue inhibitors of MMPs. Platelets are a primary blood reservoir of CD154. Here we studied, the impact of the CD154/CD40 pathway on MMP‐9 expression by cultured human podocytes. The role of CD40/CD154 was evaluated upon exposure of podocytes to recombinant human CD154 (rhCD154) or activated platelet supernatants from healthy human subjects. We first showed by protein and mRNA expression that CD40 was synthesized by podocytes and detectable on kidney tissue sections. CD40 expression was acquired during podocyte differentiation and enhanced upon exposure to rhCD154. In podocytes, rhCD154 induced an increase of MMP‐9 production as shown by RT‐PCR, Western blot and and gelatin zymography. Activated platelet supernatants induced MMP‐9 mRNA synthesis in podocytes, an effect reduced by anti‐CD40 antibody. Our results underscore a potential role for platelets through the CD40/CD154 signaling pathway in the control of GBM synthesis and degradation, via its regulatory role on MMP‐9 production. CD154 secretion by activated platelets may contribute to GBM alterations in proteinuric nephropathies. J. Cell. Biochem. 117: 2737–2747, 2016.

Renal Doppler in the management of the acute kidney injury in intensive care unit

predictive value of Doppler-based renal arterial resistive index. Intensive Care Med 2006;32:1553-9. [6] Radermacher J, Mengel M, Ellis S, et al. The renal arterial resistance index and renal allograft survival. N Engl J Med 2003;349:115-24. [7] Deruddre S, Cheisson G, Mazoit JX, et al. Renal arterial resistance in septic shock: effects of increasing mean arterial pressure with norepinephrine on the renal resistive index assessed with Doppler ultrasonography. Intensive Care Med 2007;33:1557-62.