Paolo Pelaia

Fluid balance and urine volume are independent predictors of mortality in acute kidney injury

IntroductionIn ICUs, both fluid overload and oliguria are common complications associated with increased mortality among critically ill patients, particularly in acute kidney injury (AKI). Although fluid overload is an expected complication of oliguria, it remains unclear whether their effects on mortality are independent of each other. The aim of this study is to evaluate the impact of both fluid balance and urine volume on outcomes and determine whether they behave as independent predictors of mortality in adult ICU patients with AKI.MethodsWe performed a secondary analysis of data from a multicenter, prospective cohort study in 10 Italian ICUs. AKI was defined by renal sequential organ failure assessment (SOFA) score (creatinine >3.5 mg/dL or urine output (UO) <500 mL/d). Oliguria was defined as a UO <500 mL/d. Mean fluid balance (MFB) and mean urine volume (MUV) were calculated as the arithmetic mean of all daily values. Use of diuretics was noted daily. To assess the impact of MFB and MUV on mortality of AKI patients, multivariate analysis was performed by Cox regression.ResultsOf the 601 included patients, 132 had AKI during their ICU stay and the mortality in this group was 50%. Non-surviving AKI patients had higher MFB (1.31 ± 1.24 versus 0.17 ± 0.72 L/day; P <0.001) and lower MUV (1.28 ± 0.90 versus 2.35 ± 0.98 L/day; P <0.001) as compared to survivors. In the multivariate analysis, MFB (adjusted hazard ratio (HR) 1.67 per L/day, 95%CI 1.33 to 2.09; <0.001) and MUV (adjusted HR 0.47 per L/day, 95%CI 0.33 to 0.67; <0.001) remained independent risk factors for 28-day mortality after adjustment for age, gender, diabetes, hypertension, diuretic use, non-renal SOFA and sepsis. Diuretic use was associated with better survival in this population (adjusted HR 0.25, 95%CI 0.12 to 0.52; <0.001).ConclusionsIn this multicenter ICU study, a higher fluid balance and a lower urine volume were both important factors associated with 28-day mortality of AKI patients.

Levosimendan for resuscitating the microcirculation in patients with septic shock: a randomized controlled study.

IntroductionThe purpose of the present study was to investigate microcirculatory blood flow in patients with septic shock treated with levosimendan as compared to an active comparator drug (i.e. dobutamine). The primary end point was a difference of ≥ 20% in the microvascular flow index of small vessels (MFIs) among groups.MethodsThe study was designed as a prospective, randomized, double-blind clinical trial and performed in a multidisciplinary intensive care unit. After achieving normovolemia and a mean arterial pressure of at least 65 mmHg, 40 septic shock patients were randomized to receive either levosimendan 0.2 μg·kg-1·min-1 (n = 20) or an active comparator (dobutamine 5 μg·kg-1·min-1; control; n = 20) for 24 hours. Sublingual microcirculatory blood flow of small and medium vessels was assessed by sidestream dark-field imaging. Microcirculatory variables and data from right heart catheterization were obtained at baseline and 24 hours after randomization. Baseline and demographic data were compared by means of Mann-Whitney rank sum test or chi-square test, as appropriate. Microvascular and hemodynamic variables were analyzed using the Mann-Whitney rank sum test.ResultsMicrocirculatory flow indices of small and medium vessels increased over time and were significantly higher in the levosimendan group as compared to the control group (24 hrs: MFIm 3.0 (3.0; 3.0) vs. 2.9 (2.8; 3.0); P = .02; MFIs 2.9 (2.9; 3.0) vs. 2.7 (2.3; 2.8); P < .001). The relative increase of perfused vessel density vs. baseline was significantly higher in the levosimendan group than in the control group (dMFIm 10 (3; 23)% vs. 0 (-1; 9)%; P = .007; dMFIs 47 (26; 83)% vs. 10 (-3; 27); P < .001). In addition, the heterogeneity index decreased only in the levosimendan group (dHI -93 (-100; -84)% vs. 0 (-78; 57)%; P < .001). There was no statistically significant correlation between systemic and microcirculatory flow variables within each group (each P > .05).ConclusionsCompared to a standard dose of 5 μg·kg-1·min-1 of dobutamine, levosimendan at 0.2 μg·kg-1·min-1 improved sublingual microcirculatory blood flow in patients with septic shock, as reflected by changes in microcirculatory flow indices of small and medium vessels.Trial registrationNCT00800306.

Arterial hyperoxia and mortality in critically ill patients: a systematic review and meta-analysis

IntroductionThe safety of arterial hyperoxia is under increasing scrutiny. We performed a systematic review of the literature to determine whether any association exists between arterial hyperoxia and mortality in critically ill patient subsets.MethodsMedline, Thomson Reuters Web of Science and Scopus databases were searched from inception to June 2014. Observational or interventional studies evaluating the relationship between hyperoxia (defined as a supranormal arterial O2 tension) and mortality in adult intensive care unit (ICU) patients were included. Studies primarily involving patients with exacerbations of chronic pulmonary disease, acute lung injury and perioperative administration were excluded. Adjusted odds ratio (OR) of patients exposed versus those not exposed to hyperoxia were extracted, if available. Alternatively, unadjusted outcome data were recorded. Data on patients, study characteristics and the criteria used for defining hyperoxia exposure were also extracted. Random-effects models were used for quantitative synthesis of the data, with a primary outcome of hospital mortality.ResultsIn total 17 studies (16 observational, 1 prospective before-after) were identified in different patient categories: mechanically ventilated ICU (number of studies (k) = 4, number of participants (n) = 189,143), post-cardiac arrest (k = 6, n = 19,144), stroke (k = 2, n = 5,537), and traumatic brain injury (k = 5, n = 7,488). Different criteria were used to define hyperoxia in terms of PaO2 value (first, highest, worst, mean), time of assessment and predetermined cutoffs. Data from studies on ICU patients were not pooled because of extreme heterogeneity (inconsistency (I2) 96.73%). Hyperoxia was associated with increased mortality in post-cardiac arrest patients (OR = 1.42 (1.04 to 1.92) I2 67.73%) stroke (OR = 1.23 (1.06 to 1.43) I2 0%) and traumatic brain injury (OR = 1.41 (1.03 to 1.94) I2 64.54%). However, these results are limited by significant heterogeneity between studies.ConclusionsHyperoxia may be associated with increased mortality in patients with stroke, traumatic brain injury and those resuscitated from cardiac arrest. However, these results are limited by the high heterogeneity of the included studies.

Effect of Performance Improvement Programs on Compliance with Sepsis Bundles and Mortality: A Systematic Review and Meta-Analysis of Observational Studies

Background Several reports suggest that implementation of the Surviving Sepsis Campaign (SSC) guidelines is associated with mortality reduction in sepsis. However, adherence to the guideline-based resuscitation and management sepsis bundles is still poor. Objective To perform a systematic review of studies evaluating the impact of performance improvement programs on compliance with Surviving Sepsis Campaign (SSC) guideline-based bundles and/or mortality. Data Sources Medline (PubMed), Scopus and Intercollegiate Studies Institute Web of Knowledge databases from 2004 (first publication of the SSC guidelines) to October 2014. Study Selection Studies on adult patients with sepsis, severe sepsis or septic shock that evaluated changes in compliance to individual/combined bundle targets and/or mortality following the implementation of performance improvement programs. Interventions may consist of educational programs, process changes or both. Data Extraction Data from the included studies were extracted independently by two authors. Unadjusted binary data were collected in order to calculate odds ratios (OR) for compliance to individual/combined bundle targets. Adjusted (if available) or unadjusted data of mortality were collected. Random-effects models were used for the data synthesis. Results Fifty observational studies were selected. Despite high inconsistency across studies, performance improvement programs were associated with increased compliance with the complete 6-hour bundle (OR = 4.12 [95% confidence interval 2.95-5.76], I2 = 87.72%, k = 25, N = 50,081) and the complete 24-hour bundle (OR = 2.57 [1.74-3.77], I2 = 85.22%, k = 11, N = 45,846) and with a reduction in mortality (OR = 0.66 [0.61-0.72], I2 = 87.93%, k = 48, N = 434,447). Funnel plots showed asymmetry. Conclusions Performance improvement programs are associated with increased adherence to resuscitation and management sepsis bundles and with reduced mortality in patients with sepsis, severe sepsis or septic shock.

Early prediction of successful weaning during pressure support ventilation in chronic obstructive pulmonary disease patients

ObjectiveThe aim of this study was to examine variables for early prediction of successful weaning in chronic obstructive pulmonary disease (COPD) patients during pressure support ventilation weaning. DesignThirteen COPD patients were pro-spectively studied to compare the respiratory pattern (inspiratory time, expiratory time, total breath cycle duration, tidal volume, respiratory rate, minute ventilation), the respiratory drive (airway occlusion pressure at 0.1 sec, tidal vol-ume/inspiratory time), and blood gases after 30 mins of pressure support weaning. SettingThe study was performed in the 20-bed General Critical Care Unit of the Rome “La Sapienza” University Hospital. PatientsWe evaluated 13 consecutive COPD patients fulfilling the standard weaning criteria (including clinical status, blood gases, forced vital capacity, maximum inspiratory pressure, and spontaneous respiratory rate after a 30-min T-piece trial) in which we compared respiratory pattern, respiratory drive, and blood gases after 30 mins of pressure support weaning. Measurements and Main ResultsAfter 30 mins of pressure support ventilation weaning (pressure support level 20cm H2O), we measured respiratory pattern (airway pressure and airflow tracing), airway occlusion pressure at 0.1 sec (occluding the inspiratory line during expiration with a rubber balloon), tidal volume/in-spiratory time, maximal inspiratory pressure, and blood gases. According to the result of the weaning trial, the patients were divided into two groups (not weaned and weaned), and the statistical difference between the evaluated variables was analyzed in weaned and not weaned groups.We did not observe a significant difference in breathing pattern data and arterial blood gases between weaned and not weaned patients. By contrast, airway occlusion pressure at 0.1 sec and maximum inspiratory pressure measured after 30 mins of weaning trial appeared significantly (p <.001) different in patients in whom the weaning trial succeeded or failed. Considering maximum inspiratory pressure, we could not separate weaned from not weaned patients, while all patients showing values of airway occlusion pressure at 0.1 sec <4.5 cm H2O were easily weaned. ConclusionsThis study confirms that conventional weaning criteria are often inadequate in predicting successful weaning of COPD patients, while airway occlusion pressure at 0.1 sec during the first phase of pressure support ventilation weaning can represent a good weaning predictor. (Crit Care Med 1992; 20:366–371)

Terlipressin versus Norepinephrine to Counteract Anesthesia-induced Hypotension in Patients Treated with Renin-Angiotensin System Inhibitors: Effects on Systemic and Regional Hemodynamics

Background: Terlipressin has been suggested as the ideal drug to treat anesthesia-induced hypotension in patients under long-term renin-angiotensin system inhibitor treatment for arterial hypertension. The authors compared the effects of terlipressin and norepinephrine on systemic hemodynamic parameters and gastric mucosal perfusion using a laser Doppler flowmetry technique in patients treated with renin-angiotensin system inhibitors who experienced hypotension at induction of anesthesia. Methods: Thirty-two patients scheduled for carotid endarterectomy under general anesthesia and treated with renin-angiotensin system inhibitors had hypotension after induction of general anesthesia. They were randomized to receive 1 mg of terlipressin (n = 16) or norepinephrine infusion (n = 16) to counteract anesthesia-induced hypotension. A laser Doppler probe was introduced into the gastric lumen. All measurements were performed just before surgery, during hypotension, at 30 min, and at 4 h. Results: Terlipressin produced an increase in mean arterial pressure and a decrease in gastric mucosal perfusion detected by laser Doppler flowmetry (P < 0.05) over 30 min that were sustained for 4 h. During the infusion, norepinephrine produced an increase in mean arterial pressure and in gastric mucosal perfusion detected by laser Doppler flowmetry (P < 0.05). If compared to norepinephrine, terlipressin reduced oxygen delivery and oxygen consumption (P < 0.05) and increased arterial lactate concentrations (P < 0.05). Conclusion: This study showed the efficacy of terlipressin in the treatment of hypotension episodes in anesthetized patients chronically treated with renin-angiotensin system inhibitors, angiotensin converting-enzyme inhibitors, and angiotensin II receptor antagonists. However, the negative effects on gastric mucosal perfusion and the risk of iatrogenic oxygen supply dependency of terlipressin need to be taken into account.

Alteration of the sublingual microvascular glycocalyx in critically ill patients

Glycocalyx degradation may contribute to microvascular dysfunction and tissue hypoperfusion during systemic inflammation and sepsis. In this observational study we evaluated the alteration of the sublingual microvascular glycocalyx in 16 healthy volunteers and 50 critically ill patients. Sidestream Dark Field images of the sublingual microcirculation were automatically analyzed by dedicated software. The Perfused Boundary Region (PBR) was calculated as the dimensions of the permeable part of the glycocalyx allowing the penetration of circulating red blood cells, providing an index of glycocalyx damage. The PBR was increased in ICU patients compared to healthy controls (2.7 [2.59-2.88] vs. 2.46 [2.37-2.59]μm, p<0.0001) and tended to be higher in the 32 septic patients compared to non-septics (2.77 [2.62-2.93] vs. 2.67 [2.55-2.75]μm, p=0.05), suggesting more severe glycocalyx alterations. A PBR of 2.76 showed the best discriminative ability towards the presence of sepsis (sensitivity: 50%, specificity: 83%; area under the receiver operating characteristic curve: 0.67, 95% CI 0.52-0.82, p=0.05). A weak positive correlation was found between PBR and heart rate (r=0.3, p=0.03). In 17 septic patients, a correlation was found between PBR and number of rolling leukocytes in post-capillary venules (RL/venule) (r=0.55, p=0.02), confirming that glycocalyx shedding enhances leukocyte-endothelium interaction.

From macrohemodynamic to the microcirculation

ICU patients need a prompt normalization of macrohemodynamic parameters. Unfortunately, this optimization sometimes does not protect patients from organ failure development. Prevention or treatment of organ failure needs another target to be pursued: the microcirculatory restoration. Microcirculation is the ensemble of vessels of maximum 100 μm in diameter. Nowadays the Sidestream Dark Field (SDF) imaging technique allows its bedside investigation and a recent round-table conference established the criteria for its evaluation. First, microcirculatory derangements have been studied in sepsis: they are mainly characterized by a reduction of vessel density, an alteration of flow, and a heterogeneous distribution of perfusion. Endothelial malfunction and glycocalyx rupture were proved to be the main reasons for the observed microthrombi, capillary leakage, leukocyte rolling, and rouleaux phenomenon, even if further studies are necessary for a better explanation. Therapeutic approaches targeting microcirculation are under investigation. Microcirculatory alterations have been recently demonstrated in other diseases such as hypovolemia and cardiac failure but this issue still needs to be explored. The aim of this paper is to gather the already known information, focus the readers attention on the importance of microvascular physiopathology in critical illness, and prompt him to actively participate to achieve a more comprehensive understanding of the issue.

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.