Microcirculatory alterations during continuous renal replacement therapy in ICU: A novel view on the 'dialysis trauma' concept.

OBJECTIVE: The purpose of this study was to evaluate microcirculation over 24 h renal replacement therapy (CRRT) in critically ill patients. METHODS: We conducted a single-center, prospective, observational study, measuring microcirculation parameters, monitored by near infrared spectroscopy (NIRS) before hemodiafiltration onset (H0), and at six (H6) and 24 h (H24) during CRRT in critically ill patients. Serum Cystatin C (sCysC) and soluble (s)E-selectin levels were measured at the same time points. Twenty-eight patients [19 men (68%)] were included in the study. RESULTS: Tissue oxygen saturation (StO2, %) [76.5 ± 12.5 (H0) vs 75 ± 11 (H6) vs 70 ± 16 (H24), p = 0.04], reperfusion rate, indicating endothelial function (EF, %/sec) [2.25 ± 1.44 (H0) vs 2.1 ± 1.8 (H6) vs 1.6 ± 1.4 (H24), p = 0.02] and sCysC (mg/L) [2.7 ± 0.8 (H0) vs 2.2 ± 0.6 (H6) vs 1.8 ± 0.8 (H24), p < 0.0001] significantly decreased within the 24 h CRRT. Change of EF positively correlated with changes of sCysC within 24 h CRRT (r = 0.464, p = 0.013) while in patients with diabetes the change of StO2 correlated with dose (r = − 0.8, p = 0.01). No correlation existed between hemoglobin and temperature changes with the deteriorated microcirculation indices. sE-Selectin levels in serum were elevated; no difference was established over the 24 h CRRT period. A strong correlation existed between the sE-Selectin concentration change at H6 and H24 and the mean arterial pressure change in the same period (r = 0.77, p < 0.001). CONCLUSIONS: During the first 24 h of CRRT implementation in critically ill patients, deterioration of microcirculation parameters was noted. Microcirculatory alterations correlated with sCysC changes and with dose in patients with diabetes.

Changes in skeletal muscle microcirculation after a hemodialysis session correlates with adequacy of dialysis.

BACKGROUND: Monitoring of the microcirculation may add additional information in terms of improving the adequacy of hemodialysis (HD) for patients. Withdrawal of liquid and complement activation during a HD session reduces the external pressure on the microcirculation and leads to an increased dilatation of the peripheral capillaries. The purposes of this study were to assess the effect of a single HD or hemodiafiltration session on the thenar microcirculation in patients with end-stage renal disease (ESRD) with or without diabetes, investigate the possible relationship between changes in the microcirculation and adequacy of dialysis (including Kt/V and parameters indicating secondary hyperparathyroidism), and compare microcirculation measurements obtained from patients with ESRD and those from healthy controls. METHODS: This pilot prospective observational study including eleven patients with ESRD on maintenance HD (nine men of mean age 73±10.5 years, ten [91%] with hypertension), nine patients with ESRD on maintenance hemodiafiltration (six men of mean age 65.5±13.2 years, five [55.5%] with diabetes and four [44.5%] with hypertension), and eight healthy volunteers. Two paired microcirculation assessments were recorded for each HD patient before and after a dialysis session. Near infrared spectroscopy and the vascular occlusion test were used to assess the microcirculation, and blood work samples were collected before and after dialysis when the pump slowed down. RESULTS: Patients with ESRD showed an increase in thenar cell metabolism at rest after a 4-hour HD session, and changes in cell metabolism correlated with the Kt/V of the session. Pre-dialysis tissue oxygen saturation over the 4-hour HD session correlated with pre-dialysis serum calcium and parathyroid hormones. Vascular reactivity was lower in ESRD patients receiving HD or hemodiafiltration than in healthy controls. CONCLUSION: Improvement in skeletal muscle microcirculation noted after a HD session was related to adequacy of dialysis. Evaluation of the microcirculation may provide additional information for management of patients on HD and identify novel targets for treatment. These preliminary findings need to be tested using a larger data set.

Prediction of the renal replacement therapy requirement in mechanically ventilated critically ill patients by combining biomarkers for glomerular filtration and tubular damage.

PURPOSE: Mechanically ventilated critically ill patients with high severity score indices need a very cautious therapeutic approach. Considering that inappropriate decisions on renal replacement therapy (RRT) initiation may promote unwanted adverse effects, we evaluated whether a panel of novel and traditional renal markers is superior to conventional renal marker in predicting RRT requirements in this group of patients. METHODS: This was a prospective observational study, performed at the two distinct multidisciplinary intensive care units (ICUs) of a 1000-bed tertiary hospital. Of 310 consecutive patients, 106 patients fulfilled the inclusion criteria of the study. Urinary neutrophil gelatinase-associated lipocalin (uNGAL), serum creatinine (sCr) and serum cystatin C (sCysC) were determined on ICU admission. The predictive performance of all markers for first RRT was tested and compared based on the area under the receiver operating characteristic (ROC) curves. Time-dependent ROC curves were used to assess the earlier time point where the markers presented their maximum area under the curve (AUC). RESULTS: All studied biomarkers and acute physiology and chronic health evaluation (APACHE) II score, were significant independent predictors of RRT (uNGAL-AUC=0.73, sCysC-AUC=0.76, sCr-AUC=0.78, APACHE-AUC=0.73, P<0.0001). sCysC and sCr showed early maximum predictive ability within 10 days of ICU admission, while uNGAL and APACHE II score within 11 days of ICU admission. sCr combined with normalized (n)NGAL and sCysC combined with either nNGAL or uNGAL established best predictors for the RRT initiation (AUC-ROC=0.8). Distinguishing patients without acute kidney injury (AKI) on ICU entry, the combination of sCysC and APACHE II score proved best (AUC-ROC=0.78). CONCLUSIONS: Specific markers of kidney dysfunction and of kidney damage can be successfully combined to increase the prognostic capability for RRT initiation. The presence of AKI affects diagnostic performance. Without an established AKI on ICU admission, future RRT requirement was better predicted by the combination of illness severity with a marker of glomerular filtration rate. With AKI on ICU admission a combination of the marker of glomerular filtration rate with one of tubular injury proved best.

The impact of the heptavalent pneumococcal conjugate vaccine on the epidemiology of acute otitis media complicated by otorrhea.

BACKGROUND: The heptavalent pneumococcal conjugate vaccine (PCV7) has a considerable effect on the epidemiology of pneumococcal disease. The aim of this observational hospital-based study was to examine the effect of the PCV7 (introduced in our settings in 2004) on the epidemiology of spontaneously draining acute otitis media. METHODS: Results of all middle ear fluid cultures (n = 3446) obtained from children with acute otitis media complicated with otorrhea before the introduction of immunization (between 2000 and 2003) were compared with those (n = 2134) obtained during a similar post-PCV7 period (between 2005 and 2008). Results of cultures obtained between 2006 and 2008 were examined prospectively, whereas those obtained in previous years were retrospectively reviewed. RESULTS: Following PCV7 immunization, the rates of otorrhea visits per 10,000 emergency department visits decreased by 38% from 133 to 83 (95% confidence interval of the difference, 42-53; P < 0.001), mainly as a result of the decrease in the incidence of pneumococcal disease (48% decrease-25 vs. 13 per 10,000 emergency department visits; P < 0.001). Otorrhea due to Haemophilus influenzae decreased by 20% (20-16 per 10,000 visits; P < 0.001). Serotype 19A accounted for 1 of 47 (2%) pneumococcal strains in 2006, for 5 of 34 (15%) in 2007, and for 13 of 53 (25%) in 2008 (P for trend: 0.001). In the postvaccine years, penicillin-resistant pneumococcal strains (minimum inhibitory concentration ≥ 2 µg/mL) increased from 4% to 13% (P < 0.001). However, the proportion of pneumococci resistant to macrolides decreased (44% vs. 35%; P = 0.01). CONCLUSIONS: After the introduction of immunization, otorrhea incidents decreased considerably, mainly because of the decrease in pneumococcal disease. H. influenzae is now the predominant organism. Serotype 19A has increased significantly and is the most common nonvaccine pneumococcal serotype. Penicillin resistance has increased in recent years.

Genetic relatedness of resistant and multiresistant Streptococcus pneumoniae strains, recovered in the Athens area, to international clones.

The prevalence of resistance to antibiotics was examined among 318 Streptococcus pneumoniae strains isolated during 1998 and 1999 in a children's hospital in Athens. The rate of resistance to penicillin was 25.8% (intermediate 22%, resistant 3.8%); 42.5% of the strains were resistant to > or = 1 antibiotic and 20% were multidrug resistant. Resistance to penicillin was lowest in invasive strains (8.3%) and highest in ear isolates (31%). A review of the same microbiology laboratory's records revealed that there has been a gradual increase in penicillin resistance since 1988-1989, when it was 5%. Capsular types were determined for 77 strains resistant to > or = 1 antibiotic, and 69 (90%) of them belonged to the following five serotypes: 19F, 14, 9V, 23F, and 6B. Seventy-five strains were analyzed by pulsed-field gel electrophoresis (PFGE) and 59/75 (79%) shared five electrophoretic types. The largest cluster consisted of 19 serotype 19F strains, of which 18 were nonsusceptible to penicillin and most were multidrug resistant and shared a common and distinct electrophoretic pattern not resembling any known clone. A group of 17 strains that were nonsusceptible to penicillin belonged to serotypes 9V (10), 14 (6), and 19F (1) and shared a common PFGE type similar to the international clone Spain9V-3. Seven serotype 23F strains, of which five were multidrug resistant, belonged to the international clone Spain23F-1. Among the strains susceptible to penicillin but resistant to non-beta-lactam antibiotics, the largest cluster consisted of 13 isolates resistant to erythromycin that belonged to serotype 14 and shared an electrophoretic pattern characteristic of the clone England14-9. Finally, three serotype 6B strains were penicillin susceptible and multidrug resistant and had features similar to the Mediterranean 6B clone. The introduction and spread of several antibiotic-resistant international clones accounts at least in part for the increase in pneumococcal resistance observed in recent years in the Athens metropolitan area.