Search

This paper deals with the estimation of glucose levels in ICU patients by the application of statistical filter theory to the data provided by a commercial continuous glucose monitoring system using a microdialysis sensor. Kalman and particle filtering are applied to simple models of the glucose dynamics. The particle filter enables the joint filtering and calibration of the sensor. The results show that the proposed filters lead to significant reduction in the estimation error with computational cost well within the capabilities of modern digital equipment. Additionally, the filters can be used for the automatic recognition of sensor faults. These results show that suitable filters can help in the construction of an artificial pancreas. [ABSTRACT FROM AUTHOR]

Fungal infections are common in critically ill patients and are associated with increased morbidity and mortality. Candida spp are the most commonly isolated fungal pathogens. The last 2 decades have seen an increased incidence of fungal infections in critical illness and the emergence of new pathogenic fungal species and also the development of more effective (better bioavailability) and safer (less toxicity, fewer drug interactions) drugs. The distinction between colonization and infection can be difficult, and problems diagnosing infection may delay initiation of antifungal treatment. A number of factors have been identified that can help to distinguish patients at high risk for fungal infection. The antifungal agents that are most frequently used in the intensive care unit are the first- and second-generation azoles and the echinocandins; amphotericin B derivatives (mainly the liposomal agents) are less widely used because of adverse effects. The choice of antifungal agent in critically ill patients will depend on the aim of therapy (prophylaxis, pre-emptive, empiric, definitive), as well as on local epidemiology and specific properties of the drug (antifungal spectrum, efficacy, toxicity, pharmacokinetic/pharmacodynamic properties, cost). In this article we will review all these aspects and propose an algorithm to guide selection of antifungal agents in critically ill patients. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to measure subcutaneous tissue cortisol obtained by microdialysis (MD) in 35 mechanically ventilated septic patients. Materials and Methods: Upon intensive care unit admission, an MD catheter was inserted into the subcutaneous tissue of the thigh. Cortisol (CORT) was determined in a 5:00 to 9:00 AM microdialysate sample collected within 72 hours. Concurrently, serum total (T-CORT) and free CORT (F-CORT) were measured. The Acute Physiology and Chronic Health Evaluation (APACHE II) and Sequential Organ Failure Assessment scores were calculated. Both T-CORT less than 10 μg/dL and F-CORT less than 0.8 μg/dL were considered as indicating critical illness-related corticosteroid insufficiency. Adrenal adequacy was defined as T-CORT greater than 20 μg/dL or F-CORT greater than 2.0 μg/dL. Results: Total CORT correlated significantly with F-CORT (rs=+0.8, P < .0001).Microdialysis CORT had a lower correlation with T-CORT (rs = +0.6, P < .0001) and F-CORT (rs = +0.7, P < .0001) and a weak correlation with APACHE II score (rs=+0.4, P < .01). On the basis of MD-CORT, the patients were divided in quartiles. Although the median F-CORT and T-CORT levels were significantly different (P < .001) among the MD-CORT quartiles, there was a considerable overlap between the subgroups. All patientswith T-CORT less than 10 μg/dL and all but 3 patients with F-CORT less than 0.8 μg/dL had tissue CORT in the lower quartile. However, only 50%and 58% of patients with adequate T-CORT and F-CORT levels, respectively, had concordant MD-CORT in the highest quartile. Conclusions: Microdialysis CORT levels correlate moderately with circulating T-CORT and F-CORT. Of note, several patients presented with discrepant measurements between interstitial and circulating CORT concentrations. Thus, interstitial CORT measurements represent an additional tool to investigate the tissue CORT availability in critically ill patients. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to study the interrelationship between blood and tissue lactate in critically ill patients with or without shock admitted in a general intensive care unit. Materials and Methods: We studied 162 mechanically ventilated patients: 106 with shock (septic shock, 97; cardiogenic shock, 9) and 56 without shock (severe sepsis, 38; systemic inflammatory response syndrome, 18). A microdialysis catheter was inserted in the subcutaneous adipose tissue of the upper thigh, and interstitial fluid was collected every 4 hours for a maximum of 6 days. We assessed the relationship between tissue and blood lactate using cross-approximate entropy and cross-correlation analysis. Results: Patients with shock had higher area under the curve for blood (261 vs 175 mmol/L*hours, P < .0001) and tissue lactate (386 vs 281 mmol/L*hours, P < .0001) compared with patients without shock. The interrelationship of tissue-blood lactate, as assessed with cross-approximate entropy, was more regular in patients with shock compared with patients without shock. Cross-correlation of tissue vs blood lactate yielded higher correlation coefficients in patients with shock compared with those without shock, being higher when tissue lactate preceded blood lactate by 4 hours compared with tissue vs blood lactate with no lag time. Conclusions: In critical illness, the detailed dynamics between blood and tissue lactate are affected by the presence of shock. In patients with shock, microdialysis-assessed tissue lactate is higher compared with those without shock and may detect metabolic disturbances before these become evident in the systemic circulation. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The aim of the present study was to describe the variation in adiponectin and resistin levels, 2 adipokines with opposing effects on metabolism, in mechanically ventilated patients with sepsis and their relationships to disease severity and cytokine levels. Materials and Methods: An observational prospective study was conducted in a secondary/tertiary unit. Forty-one mechanically ventilated patients diagnosed as having sepsis were included in the study. The Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were estimated. Adiponectin, resistin, and cytokines were measured upon sepsis diagnosis and every 3 to 4 days thereafter until day 30. Adiponectin and resistin were also measured in 40 controls. Results: The patients had higher adiponectin (10.9 ± 6.1 μg/mL vs 6.0 ± 2.9 μg/mL, P < .001) and resistin (24.7 ng/mL vs 3.8 ng/mL, P < .001) levels compared with the controls. Adiponectin increased and resistin decreased significantly over time in the entire cohort. Resistin correlated with Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, interleukin (IL)-6, IL-8, and IL-10 and was significantly higher in severe sepsis/septic shock compared with sepsis. No correlations between adiponectin and clinical scores were noted. Conclusions: Adiponectin and resistin change reciprocally during the course of sepsis. Resistin relates to the severity of sepsis and the degree of inflammatory response. Adiponectin and resistin may play a critical role in the metabolic adaptations observed in sepsis. [Copyright &y& Elsevier]

Summary: Objective: This observational retrospective study aims to present early experience with tigecycline (TIG) in the treatment of infections due to multi-drug resistant (MDR) microorganisms. Methods: Adult patients included, received TIG for >5 days either as monotherapy (M group) or as presumed active monotherapy (PAM group). In the PAM group, all co-administered antimicrobial(s) were resistant in vitro against the targeted pathogen(s) or had been clinically and microbiologically failing after ≥5 days of therapy despite in vitro susceptibility. Results: Forty-five patients (35 in ICU) were treated for 28 Acinetobacter baumannii and 23 Klebsiella pneumoniae infections [21 ventilator-associated and healthcare-acquired pneumonia (VAP/HCAP), 10 bloodstream infections (BSI) and 14 surgical infections (SI)]. Successful overall clinical outcome was 80%, i.e. 81.8% in M group, 78.3% in PAM group, 90.5% in VAP/HCAP, 80% in BSI, 64.3% in SI and 85% in the cases with septic shock. Superinfections from Enterobacteriaceae inherently resistant to tigecycline occurred in 31.8% of M and 13% of PAM group (p <0.001). Conclusion: TIG represents a promising option in infections from MDR pathogens, however, further clinical experience is required. [Copyright &y& Elsevier]

Abstract: Purpose: Prone positioning is used to improve oxygenation in patients with hypoxemic respiratory failure (HRF). However, its role in clinical practice is not yet clearly defined. The aim of this meta-analysis was to assess the effect of prone positioning on relevant clinical outcomes, such as intensive care unit (ICU) and hospital mortality, days of mechanical ventilation, length of stay, incidence of ventilator-associated pneumonia (VAP) and pneumothorax, and associated complications. Methods: We used literature search of MEDLINE, Current Contents, and Cochrane Central Register of Controlled Trials. We focused only on randomized controlled trials reporting clinical outcomes in adult patients with HRF. Four trials met our inclusion criteria, including 662 patients randomized to prone ventilation and 609 patients to supine ventilation. Results: The pooled odds ratio (OR) for the ICU mortality in the intention-to-treat analysis was 0.97 (95% confidence interval [CI], 0.77-1.22), for the comparison between prone and supine ventilated patients. Interestingly, the pooled OR for the ICU mortality in the selected group of the more severely ill patients favored prone positioning (OR, 0.34; 95% CI, 0.18-0.66). The duration of mechanical ventilation and the incidence of pneumothorax were not different between the 2 groups. The incidence of VAP was lower but not statistically significant in patients treated with prone positioning (OR, 0.81; 95% CI, 0.61-1.10). However, prone positioning was associated with a higher risk of pressure sores (OR, 1.49; 95% CI, 1.17-1.89) and a trend for more complications related to the endotracheal tube (OR, 1.30; 95% CI, 0.94-1.80). Conclusions: Despite the inherent limitations of the meta-analytic approach, it seems that prone positioning has no discernible effect on mortality in patients with HRF. It may decrease the incidence of VAP at the expense of more pressure sores and complications related to the endotracheal tube. However, a subgroup of the most severely ill patients may benefit most from this intervention. [Copyright &y& Elsevier]

We report on two patients who developed large left-sided pleural effusions in association with hemodynamic compromise. In both cases transthoracic echocardiography demonstrated left ventricular diastolic collapse confirming our clinical suspicion of cardiac tamponade. Large-volume thoracentesis in the first case and thoracotomy with drainage of the pleural collection in the second case resulted in immediate hemodynamic improvement. Our report shows that large pleural effusions can result in impaired cardiac filling and a tamponade-like physiology. Thoracentesis in this setting can lead to rapid improvement of the hemodynamic profile. [Copyright &y& Elsevier]

Abstract: Background: Reduced coronary velocity flow reserve (CFR) is associated with poor outcome in patients with cardiovascular disease. We investigated whether CFR is associated with tissue ischemia and acidosis, impaired myocardial deformation and adverse outcome in patients with septic shock. Methods: In 70 mechanically-ventilated patients with septic shock, we examined: a) S′ and E′ mitral annular velocities using tissue Doppler imaging (TDI), b) CFR of the left anterior descending artery after adenosine infusion using transesophageal Doppler echocardiography and c) lactate, pyruvate and glycerol in tissue by means of a microdialysis (MD) catheter inserted into the subcutaneous adipose tissue as markers of tissue ischemia and acidosis. SOFA and APACHE II prognostic scores and mortality in the intensive care unit (ICU) were recorded. Results: Reduced CFR, S′ and E′ as well as increased E/E′ correlated with increased SOFA, APACHE II and MD lactate to pyruvate ratio (p<0.05 for all correlations). Impaired TDI markers also correlated with increased MD glycerol (p<0.05). Reduced CFR correlated with decreased E′ (p<0.05). CFR was 1.8±0.42 in non-survivors (n=34) versus 2.08±0.44 in survivors (p=0.007). A CFR<1.90 predicted mortality with sensitivity of 70% and specificity of 69% (area under the curve 77%; p=0.003). CFR had an additive value to APACHE (chi-square change: 4.358, p=0.03) and SOFA (chi-square change: 3.692, p=0.04) for the prediction of mortality. Conclusion: Tissue ischemia and acidosis is a common pathophysiological link between decreased CFR and impaired LV myocardial deformation in septic shock. CFR is an additive predictor of ICU mortality to traditional risk scores in septic shock. [Copyright &y& Elsevier]

Abstract: We aimed to investigate if angiopoietin-2 (Ang-2) participates in the septic process and what may be the role of monocytes as a site of release of Ang-2 in sepsis. Concentrations of Ang-2 were estimated in sera and in supernatants of monocytes derived form one already described cohort of 90 patients with septic syndrome due to ventilator-associated pneumonia (VAP). Mononuclear cells of 17 healthy volunteers were stimulated by serum of patients in the presence or absence of various intracellular pathway inhibitors. Ang-2 gene expression after stimulation was also tested. Ang-2 was higher in patients with septic shock compared to patients with sepsis, severe sepsis and controls. Ang-2 was significantly increased in non-survivors compared with survivors. Serum levels greater than 9700pg/ml were accompanied by a 3.254 odds ratio for death (p: 0.033). Ang-2 release from monocytes of septic patients was slightly decreased after stimulation with lipopolysaccharide (LPS) of Escherichia coli O55:B5. Release of Ang-2 from healthy mononuclear cells was stimulated by serum of patients with shock but not by serum of non-shocked patients (p: 0.016). Release was decreased by LPS; increased in the presence of a TLR4 antagonist; and decreased by anti-TNF antibody. RNA transcripts of PBMCs after stimulation with serum of patients with septic shock were higher than those after LPS stimulation. It is concluded that Ang-2 is increased in serum in the event of septic shock and that its increase is related to unfavorable outcome. It seems that a circulating factor may exist in the serum of patients with septic shock that stimulates gene expression and subsequent release of Ang-2 from monocytes. TLR4 and TNFα modulate release of Ang-2. [Copyright &y& Elsevier]

Abstract: Intoduction: Increased levels of plasminogen activator inhibitor-1 (PAI-1) have been associated with worse outcome in ALI/ARDS. A single guanosine insertion/deletion (4G/5G) polymorphism in the promoter region of the PAI-1 gene, may play an important role in the regulation of PAI-1 expression. The objective of the study was to evaluate the effect of this polymorphism on the outcome of critically ill patients with ALI/ARDS. Materials and Methods: 52 consecutive ventilated patients with ALI/ARDS were studied. Bronchoalveolar lavage was performed within 48 hours from diagnosis. Measurement of plasma and BALF PAI-1 activity and D-dimers levels, and 4G/5G genotyping of PAI-1 were carried out. The primary outcome was 28-day mortality, and secondary outcomes included organ dysfunction and ventilator-free days. Results: 17 patients were homozygotes for the 4G allele. Severity scores were not different between subgroups upon study enrollment. 28-day mortality was 70.6% and 42.9% for the 4G-4G and the non-4G-4G patients, respectively (p=0.06). PAI-1 activity levels and D-dimer in plasma and BALF were not significantly different between the 4G-4G and the non-4G-4G subgroups. In the multivariate analysis, genotype 4G/4G was the only variable independently associated with 28-day mortality (Odds Ratio=9.95, 95% CI: 1.79-55.28, p=0.009). Furthermore, genotype 4G/4G and plasma PAI-1 activity levels were independently negatively associated with ventilator free days (p=0.033 and p=0.008, respectively). Conclusions: ALI/ARDS patients, homozygous for the 4G allele of the PAI-1 gene, experienced higher 28-day mortality. This genotype was associated with a reduction in the number of days of unassisted ventilation and was inversely associated with the number of days without organ failure. [Copyright &y& Elsevier]

Abstract: The serine protease activated protein C (APC) possesses prominent anticoagulant and anti-inflammatory actions. In this study, we investigated the effect of inhaled recombinant human (rh) APC in a murine lung injury model. Animals inhaled 10 mg of Pseudomonas lipopolysaccharide (LPS) in 3 mL normal saline (NS); 30 min prior to LPS, mice were pretreated with inhaled rhAPC (4 mg/3 mL NS; APC+LPS group) or NS (LPS group). A control animal group inhaled vehicle (NS) twice. 24 h later, total cells and cell-types, protein content, and the cytokines tumor necrosis factor-α, interleukin (IL)-6, macrophage inflammatory protein-1α, and mouse keratinocyte-derived chemokine (a homolog of human IL-8) were estimated in bronchoalveolar lavage fluid (BALF). Lung pathology given as total histology score (THS), wet/dry lung weight ratios, and lung vascular cell adhesion molecule (VCAM)-1 expression were additionally assessed. rhAPC inhalation attenuated the aerosolized LPS-induced increases of: total cells, neutrophils and macrophages in BALF, lung tissue VCAM-1 protein levels, and THS. Total protein levels and cytokines in BALF, and wet/dry weight ratios were increased in the LPS group, but rhAPC pretreatment did not significantly alter the LPS-induced responses. In conclusion, in this murine septic model of lung injury, inhaled rhAPC appears to attenuate lung inflammation, without reversing the observed increases in lung permeability and BALF cytokines. This effect may be associated with leukocyte trafficking modifications, related, at least in part, to VCAM-1 reduction. [Copyright &y& Elsevier]