Vincenzo Gabbanelli

Microcirculatory effects of the transfusion of leukodepleted or non-leukodepleted red blood cells in patients with sepsis: a pilot study

IntroductionMicrovascular alterations impair tissue oxygenation during sepsis. A red blood cell (RBC) transfusion increases oxygen (O2) delivery but rarely improves tissue O2 uptake in patients with sepsis. Possible causes include RBC alterations due to prolonged storage or residual leukocyte-derived inflammatory mediators. The aim of this study was to compare the effects of two types of transfused RBCs on microcirculation in patients with sepsis.MethodsIn a prospective randomized trial, 20 patients with sepsis were divided into two separate groups and received either non-leukodepleted (n = 10) or leukodepleted (n = 10) RBC transfusions. Microvascular density and perfusion were assessed with sidestream dark field (SDF) imaging sublingually, before and 1 hour after transfusions. Thenar tissue O2 saturation (StO2) and tissue hemoglobin index (THI) were determined with near-infrared spectroscopy, and a vascular occlusion test was performed. The microcirculatory perfused boundary region was assessed in SDF images as an index of glycocalyx damage, and glycocalyx compounds (syndecan-1, hyaluronan, and heparan sulfate) were measured in the serum.ResultsNo differences were observed in microvascular parameters at baseline and after transfusion between the groups, except for the proportion of perfused vessels (PPV) and blood flow velocity, which were higher after transfusion in the leukodepleted group. Microvascular flow index in small vessels (MFI) and blood flow velocity exhibited different responses to transfusion between the two groups (P = 0.03 and P = 0.04, respectively), with a positive effect of leukodepleted RBCs. When within-group changes were examined, microcirculatory improvement was observed only in patients who received leukodepleted RBC transfusion as suggested by the increase in De Backer score (P = 0.02), perfused vessel density (P = 0.04), PPV (P = 0.01), and MFI (P = 0.04). Blood flow velocity decreased in the non-leukodepleted group (P = 0.03). THI and StO2 upslope increased in both groups. StO2 and StO2 downslope increased in patients who received non-leukodepleted RBC transfusions. Syndecan-1 increased after the transfusion of non-leukodepleted RBCs (P = 0.03).ConclusionsThis study does not show a clear superiority of leukodepleted over non-leukodepleted RBC transfusions on microvascular perfusion in patients with sepsis, although it suggests a more favorable effect of leukodepleted RBCs on microcirculatory convective flow. Further studies are needed to confirm these findings.Trial registrationClinicalTrials.gov, NCT01584999

The impact of a clinical information system in an intensive care unit.

PurposeAlthough clinical information systems (CISs) have been available and implemented in many Intensive care Units (ICUs) for more than a decade, there is little objective evidence of their impact on the quality of care and staff perceptions. This study was performed to compare time spent charting with pen and paper patient data versus time spent with the new electronic CIS and to evaluate staff perceptions of a CIS in an ICU.Materials and MethodsTime spent every day was calculated for each patient, for 7 days, for recording on the paper vital signs and physician therapeutic orders and time spent for computing fluid balance and scores. This time was then compared with time required to make the same activities by means of CIS, 10 months after its introduction in ICU. Four years after the installation of CIS, a questionnaire was given to all staff attending to the ICU to evaluate their opinions of the CIS.ResultsThe CIS took less staff time to record common ICU data than paper records (3 ± 2 minutes/day versus 37 ± 7 minutes/day respectively, P< 0.001). Perceptions of the CIS were that computers promoted an improving charting quality.ConclusionsThe implementation of a CIS was associated with a reduced time spent for daily activity and a positive medical and nursing staff perception.

RIFLE-Based Data Collection/Management System Applied to a Prospective Cohort Multicenter Italian Study on the Epidemiology of Acute Kidney Injury in the Intensive Care Unit

The epidemiology of acute kidney injury (AKI) has been difficult to explore in the past, due to different definitions across various studies. Nevertheless, this is a very important topic today in light of the high morbidity and mortality of critically ill patients presenting renal dysfunction during their stay in the intensive care unit (ICU). The case mix has changed over the years, and AKI is a common problem in critically ill patients often requiring renal replacement therapy (RRT). The RIFLE and AKIN initiatives have provided a unifying definition for AKI, making possible large retrospective studies in different countries. The present study aims at validating a unified web-based data collection and data management tool based on the most recent AKI definition/classification system. The interactive database is designed to elucidate the epidemiology of AKI in a critically ill population. As a test, we performed a prospective observational multicenter study designed to prospectively evaluate all incident admissions in ten ICUs in Italy and the relevant epidemiology of AKI. Thus, a simple user-friendly web-based data collection tool was created with the scope to serve for this study and to facilitate future multicenter collaborative efforts. We enrolled 601 consecutive incident patients into the study; 25 patients with end-stage renal disease were excluded, leaving 576 patients for analysis. The median age was 66 (IQR 53–76) years, 59.4% were male, while median Simplified Acute Physiology Score II and Acute Physiology and Chronic Health Evaluation II scores were 43 (IQR 35–54) and 18 (IQR 13–24), respectively. The most common diagnostic categories for ICU admission were: respiratory (27.4%), followed by neurologic (17%), trauma (14.4%), and cardiovascular (12.1%). Crude ICU and hospital mortality were 21.7% and median ICU length of stay was 5 (IQR 3–14) days. Of 576 patients, 246 patients (42.7%) had AKI within 24 h of ICU admission, while 133 developed new AKI later during their ICU stay. RIFLE-initial class was Risk in 205 patients (54.1%), Injury in 99 (26.1%) and Failure in 75 (19.8%). Progression of AKI to a worse RIFLE class was seen in 114 patients (30.8% of AKI patients). AKI patients were older, with higher frequency of common risk factors. 116 AKI patients (30.6%) fulfilled criteria for sepsis during their ICU stay, compared to 33 (16.7%) of non-AKI patients (p < 0.001). 48 patients (8.3%) were treated with RRT in the ICU. Patients were started on RRT a median of 2 (IQR 0–6) days after ICU admission. AKI patients were started on RRT a median of 1 (IQR 0–4) day after fulfilling criteria for AKI. Median duration of RRT was 5 (IQR 2–10) days. AKI patients had a higher crude ICU mortality (28.8 vs. 8.1%, non-AKI; p < 0.001) and longer ICU length of stay (median 7 vs. 3 days, non-AKI; p < 0.001). Crude ICU mortality and ICU length of stay increased with greater severity of AKI. 225 (59.4% of AKI patients) had complete recovery of renal function, with a serum creatinine at time of ICU discharge which was ≤120% of baseline; an additional 51 AKI patients (13.5%) had partial renal recovery, while 103 (27.2%) had not recovered renal function at the time of death or ICU discharge. The study supports the use of RIFLE as an optimal classification system to stage AKI severity. AKI is indeed a deadly complication for ICU patients, where the level of severity is correlated with mortality and length of stay. The tool developed for data collection was user-friendly and easy to implement. Some of its features, including a RIFLE class alert system, may help the treating physician to systematically collect AKI data in the ICU and possibly may guide specific decisions on the institution of RRT.

Recombinant activated protein C treatment improves tissue perfusion and oxygenation in septic patients measured by near-infrared spectroscopy

IntroductionThe purpose was to test the hypothesis that muscle perfusion, oxygenation, and microvascular reactivity would improve in patients with severe sepsis or septic shock during treatment with recombinant activated protein C (rh-aPC) (n = 11) and to explore whether these parameters are related to macrohemodynamic indices, metabolic status or Sequential Organ Failure Assessment (SOFA) score. Patients with contraindications to rh-aPC were used as a control group (n = 5).Materials and methodsPatients were sedated, intubated, mechanically ventilated, and hemodynamically monitored with the PiCCO system. Tissue oxygen saturation (StO2) was measured using near-infrared spectroscopy (NIRS) during the vascular occlusion test (VOT). Baseline StO2 (StO2 baseline), rate of decrease in StO2 during VOT (StO2 downslope), and rate of increase in StO2 during the reperfusion phase were (StO2 upslope) determined. Data were collected before (T0), during (24 hours (T1a), 48 hours (T1b), 72 hours (T1c) and 96 hours (T1d)) and 6 hours after stopping rh-aPC treatment (T2) and at the same times in the controls. At every assessment, hemodynamic and metabolic parameters were registered and the SOFA score calculated.ResultsThe mean ± standard deviation Acute Physiology and Chronic Health Evaluation II score was 26.3 ± 6.6 and 28.6 ± 5.3 in rh-aPC and control groups, respectively. There were no significant differences in macrohemodynamic parameters between the groups at all the time points. In the rh-aPC group, base excess was corrected (P < 0.01) from T1a until T2, and blood lactate was significantly decreased at T1d and T2 (2.8 ± 1.3 vs. 1.9 ± 0.7 mmol/l; P < 0.05). In the control group, base excess was significantly corrected at T1a, T1b, T1c, and T2 (P < 0.05). The SOFA score was significantly lower in the rh-aPC group compared with the controls at T2 (7.9 ± 2.2 vs. 12.2 ± 3.2; P < 0.05). There were no differences between groups in StO2 baseline. StO2 downslope in the rh-aPC group decreased significantly at all the time points, and at T1b and T2 (-16.5 ± 11.8 vs. -8.1 ± 2.4%/minute) was significantly steeper than in the control group. StO2 upslope increased and was higher than in the control group at T1c, T1d and T2 (101.1 ± 62.1 vs. 54.5 ± 23.8%/minute) (P < 0.05).ConclusionsTreatment with rh-aPC may improve muscle oxygenation (StO2 baseline) and reperfusion (StO2 upslope) and, furthermore, rh-aPC treatment may increase tissue metabolism (StO2 downslope). NIRS is a simple, real-time, non-invasive technique that could be used to monitor the effects of rh-aPC therapy at microcirculatory level in septic patients.

Thermodilution vs pressure recording analytical method in hemodynamic stabilized patients

PURPOSE Many mini-invasive devices to monitor cardiac output (CO) have been introduced and, among them, the pressure recording analytical method (PRAM). The aim of this study was to assess the agreement of PRAM with the intermittent transpulmonary thermodilution and continuous pulmonary thermodilution in measuring CO in hemodynamically stabilized patients. MATERIALS AND METHODS This is a prospective clinical study in a mixed medical-surgical intensive care unit (ICU) and in a postcardiac surgical ICU. Forty-eight patients were enrolled: 32 patients to the medical-surgical ICU monitored with PiCCO (Pulsion Medical System AG, Munich, Germany) and 16 were cardiac patients monitored with Vigilance (Edwards Lifesciences, Irvine, CA). RESULTS A total of 112 measurements were made. Ninety-six comparisons of paired CO measurements were made in patients hospitalized in medical-surgical ICU; 16, in cardiac surgical patients. The mean Vigilance-CO was 4.49 ± 0.99 L/min (range, 2.80-5.90 L/min), and the mean PRAM-CO was 4.27 ± 0.88 L/min (range, 2.85-6.19 L/min). The correlation coefficient between Vigilance-CO and PRAM-CO was 0.83 (95% confidence interval, 0.57-0.94; P < .001). The bias was 0.22 ± 0.55 L/min with limits of agreement between 0.87 and 1.30 L/min. The percentage error was 25%. Mean TP-CO was 6.78 ± 2.04 L/min (range, 4.12-11.27 L/min), and the mean PRAM-CO was 6.11 ± 2.18 L/min (range, 2.82-10.90 L/min). The correlation coefficient between PiCCO-CO and PRAM-CO was 0.91 (95% confidence interval, 0.83-0.96; P < .0001). The bias was 0.67 ± 0.89 L/min with limits of agreement -1.07 and 2.41 L/min. The coefficient of variation for PiCCO was 4% ± 2%, and the coefficient of variation for PRAM was 10% ± 8%. The percentage error was 28%. CONCLUSIONS The PRAM system showed good agreement with pulmonary artery catheter and PiCCO in hemodynamically stabilized patients.

Increasing microcirculation after drotrecogin alfa (activated)

In severe sepsis, microcirculatory dysfunction caused by inflammation, endothelial activation and procoagulant response leads to mithocondrial dysfunction (termed microcirculatory and mitochondrial distress syndrome). If undetected, this condition can lead to parenchymal cellular distress and so to organ failure. As regional and microcirculatory distress are independent of systemic hemodynamic-derived and oxygen-derived variables, we recorded the course of microvascular parameters with a Microscan Video Microscope (Microvision, The Netherlands) in four patients with severe sepsis. We studied the sublingual region because of its embryologic correlation to splanchnic circulation, its thin mucosa. The instrument used a new improved imaging modality for observation of the microcirculation called sidestream dark-field imaging. We consider here four patients with severe sepsis related to esophagectomy, severe polytrauma with splanchnic organ damage and mediastinitis treated with drotrecogin alpha (activated) (DA) at 24 μg/kg/hour for 96 hours. The patients were admitted to the ICU, ventilated mechanically, monitored hemodynamically via a PICCO system and supported with dobutamine. Videomicroscopy was made before administration of DA and was repeated every 24 hours during the treatment with DA and at 24 hours after its suspension. We recorded values of blood pressure, cardiac function, lactate levels, acid–base balance, temperature and dobutamine dosage. At admission the sublingual microcirculation showed a low capillary density, vessel heterogeneity with a qualitative low flow and flow–no flow. After the first 24 hours from the beginning of DA infusion, sublingual flow showed an increase of vessel density, particularly of the number of small vessels, and the number of continuously perfused vessels increased during and post therapy with DA. We analyzed the microvascular flow with a simple semi-quantitative method dividing the images into four equal quadrants and quantificating flow (hyperdynamic, continuous, sluggish, flow–no flow, no flow) for each cohort of vessel diameter (small, medium, large). We analyzed the mean value of results of three images for each patient pre and post DA therapy. Data are presented as the median. Before starting therapy with DA, the microvascular flow index (MFI) was 2.06 for small vessels, 2.09 for medium vessels, and 2.37 for large vessels. After DA infusion, the MFI was 3, 3, and 3, respectively, for small, medium and large vessels. Differences between groups were assessed using the Mann–Whitney U test. We showed a statistically significant difference with P < 0.0001 between MFI before and post DA therapy. We demonstrated a quantitative and qualitative improvement of sublingual microcirculation with an increase of capillary density distribution (area–width) and average velocity versus vessel width. The course of microvascular blood flow may play an important role in sepsis and septic shock because of its relation to the development of multiple organ failure and death. Several studies have demonstrated that changes in microvascular perfusion are an independent predictor of outcome. The improvement of the microcirculation and vascular tone in septic shock by DA is probably related to its anticoagulant/antithrombotic and antiinflammatory action, to the decrease of TNFα production and inhibition of iNOS induction, and to improvement of endothelial barrier function and inhibition of chemotaxis, but further investigations are required to elucidate the exact mechanisms. These observations could suggest that DA could have a particular interest in the early management of severe sepsis.