Determining rhythmicity and determinism of temperature curves in septic and non-septic critically ill patients through chronobiological and recurrence quantification analysis: a pilot study.

BACKGROUND: A few studies have demonstrated that critically ill patients exhibit circadian deregulation and reduced complexity of different time series, such as temperature. RESULTS: In this prospective study, we enrolled 21 patients divided into three groups: group A (N = 10) included subjects who had septic shock at the time of ICU entry, group B (N = 6) included patients who developed septic shock during ICU stay, and group C consisted of 5 non-septic critically ill patients. Core body temperature (CBT) was recorded for 24 h at a rate of one sample per hour (average of CBT for that hour) and during different occasions: upon ICU entry and exit in groups A and C and upon entry, septic shock development, and exit in group B. Markers of circadian rhythmicity included mean values, amplitude that is the difference between peak and mean values, and peak time. Furthermore, recurrence quantification analysis (RQA) was employed for assessing different markers of complexity of temperature signals. Patients from group C exhibited higher temperature amplitude upon entry (0.45 ± 0.19) in relation with both groups A (0.28 ± 0.18, p < 0.05) and B (0.32 ± 0.13, p < 0.05). Circadian features did not differ within all groups. Temperature amplitude in groups B and C upon entry was negatively correlated with SAPS II (r = - 0.72 and - 0.84, p < 0.003) and APACHE II scores (r = - 0.70 and - 0.63, p < 0.003), respectively, as well as duration of ICU and hospital stay in group B (r = - 0.62 and - 0.64, p < 0.003) and entry SOFA score in group C (r = - 0.82, p < 0.003). Increased periodicity of CBT was found for all patients upon exit related to entry in the ICU. Different RQA features indicating periodic patterns of change of entry CBT were negatively correlated with severity of disease and length of ICU stay for all patients. CONCLUSIONS: Increased temperature rhythmicity during ICU entry was related with lower severity of disease and better clinical outcomes, whereas the more deterministic CBT patterns were found in less critically ill patients with shorter ICU stay.

Design and Implementation of the Intensive Care Unit Quality Management Registry: Monitoring Quality and Cost of an Adult Intensive Care Unit in a Greek State Hospital.

Intensive care electronic registries have been instrumental in quality measurement, improvement, and assurance of intensive care. In this article, the development and pilot implementation of the Intensive Care Unit Quality Management Registry are described, with a particular focus on monitoring the quality and operational cost in an adult ICU at a northern Greek state hospital. A relational database was developed for a hospital ICU so that qualitative and financial data are recorded for further analysis needed for planning quality care improvement and enhanced efficiency. Key features of this database registry were low development cost, user friendliness, maximum data security, and interoperability in existing hospital information systems. The database included patient demographics, nursing and medical parameters, and quality and performance indicators as established in many national registries worldwide. Cost recording was based on a mixed approach: at patient level ("bottom-up" method) and at department level ("top-down" method). During the pilot phase of the database operation, regular monitoring of quality and cost data revealed several fields of quality excellence, while indicating room for improvement for others. Parallel recording and trending of multiple parameters showed that the database can be utilized for optimum ICU quality and cost management and also for further research purposes by nurses, physicians, and administrators.

Gut failure in critical care: old school versus new school.

The concept of bacterial translocation and gut-origin sepsis as causes of systemic infectious complications and multiple organ deficiency syndrome in surgical and critically ill patients has been a recurring issue over the last decades attracting the scientific interest. Although gastrointestinal dysfunction seemingly arises frequently in intensive care unit patients, it is usually underdiagnosed or underestimated, because the pathophysiology involved is incompletely understood and its exact clinical relevance still remains controversial with an unknown yet probably adverse impact on the patients' outcome. The purpose of this review is to define gut-origin sepsis and related terms, to describe the mechanisms leading to gut-derived complications, and to illustrate the therapeutic options to prevent or limit these untoward processes.

Bloodstream infections and sepsis in Greece: over-time change of epidemiology and impact of de-escalation on final outcome.

BACKGROUND: Choice of empirically prescribed antimicrobials for sepsis management depends on epidemiological factors. The epidemiology of sepsis in Greece was studied in two large-periods. METHODS: Sepsis due to bloodstream infections (BSI) from July 2006 until March 2013 was recorded in a multicenter study in 46 departments. Patients were divided into sepsis admitted in the emergencies and hospitalized in the general ward (GW) and sepsis developing after admission in the Intensive Care Unit (ICU). The primary endpoints were the changes of epidemiology and the factors related with BSIs by multidrug-resistant (MDR) pathogens; the secondary endpoint was the impact of de-escalation on antimicrobial therapy. RESULTS: 754 patients were studied; 378 from 2006-2009 and 376 from 2010-2013. Major differences were recorded between periods in the GW. They involved increase of: sepsis severity; the incidence of underlying diseases; the incidence of polymicrobial infections; the emergence of Klebsiella pneumoniae as a pathogen; and mortality. Factors independently related with BSI by MDR pathogens were chronic hemofiltration, intake of antibiotics the last three months and residence into long-term care facilities. De-escalation in BSIs by fully susceptible Gram-negatives did not affect final outcome. Similar epidemiological differences were not found in the ICU; MDR Gram-negatives predominated in both periods. CONCLUSIONS: The epidemiology of sepsis in Greece differs in the GW and in the ICU. De-escalation in the GW is a safe strategy.

Hemoptysis due to a mycotic pulmonary artery aneurysm in an injecting drug user.

Infected aneurysms of the pulmonary artery are a rare consequence of injected drug use. Hemoptysis of pulmonary arterial origin is also infrequent; however, the mortality is as high as 50%. We report here a case of hemoptysis in an intravenous drug user, caused by a pulmonary artery aneurysm due to septic microemboli, originating from a groin abscess. We highlight the importance of recognizing and treating thromboembolic complications associated with deep venous thrombosis in injecting drug users.

Association of heart rate variability and inflammatory response in patients with cardiovascular diseases: current strengths and limitations.

Many experimental and clinical studies have confirmed a continuous cross-talk between both sympathetic and parasympathetic branches of autonomic nervous system and inflammatory response, in different clinical scenarios. In cardiovascular diseases, inflammation has been proven to play a pivotal role in disease progression, pathogenesis and resolution. A few clinical studies have assessed the possible inter-relation between neuro-autonomic output, estimated with heart rate variability analysis, which is the variability of R-R in the electrocardiogram, and different inflammatory biomarkers, in patients suffering from stable or unstable coronary artery disease (CAD) and heart failure. Moreover, different indices derived from heart rate signals' processing, have been proven to correlate strongly with severity of heart disease and predict final outcome. In this review article we will summarize major findings from different investigators, evaluating neuro-immunological interactions through heart rate variability analysis, in different groups of cardiovascular patients. We suggest that markers originating from variability analysis of heart rate signals seem to be related to inflammatory biomarkers. However, a lot of open questions remain to be addressed, regarding the existence of a true association between heart rate variability and autonomic nervous system output or its adoption for risk stratification and therapeutic monitoring at the bedside. Finally, potential therapeutic implications will be discussed, leading to autonomic balance restoration in relation with inflammatory control.

Short- vs long-duration antibiotic regimens for ventilator-associated pneumonia: a systematic review and meta-analysis.

BACKGROUND: We performed a systematic review and meta-analysis of short- vs long-duration antibiotic regimens for ventilator-associated pneumonia (VAP). METHODS: We searched PubMed and Cochrane Central Registry of Controlled Trials. Four randomized controlled trials (RCTs) comparing short (7-8 days) with long (10-15 days) regimens were identified. Primary outcomes included mortality, antibiotic-free days, and clinical and microbiologic relapses. Secondary outcomes included mechanical ventilation-free days, duration of mechanical ventilation, and length of ICU stay. RESULTS: All RCTs included mortality data, whereas data on relapse and antibiotic-free days were provided in three and two out of four RCTs, respectively. No difference in mortality was found between the compared arms (fixed effect model [FEM]: OR = 1.20; 95% CI, 0.84-1.72; P = .32). There was an increase in antibiotic-free days in favor of the short-course treatment with a pooled weighted mean difference of 3.40 days (random effects model: 95% CI, 1.43-5.37; P < .001). There was no difference in relapses between the compared arms, although a strong trend to lower relapses in the long-course treatment was observed (FEM: OR = 1.67; 95% CI, 0.99-2.83; P = .06). No difference was found between the two arms regarding the remaining outcomes. Sensitivity analyses yielded similar results. CONCLUSIONS: Short-course treatment of VAP was associated with more antibiotic-free days. No difference was found regarding mortality and relapses; however, a strong trend for fewer relapses was observed in favor of the long-course treatment, being mostly driven by one study in which the observed relapses were probably more microbiologic than clinical. Additional research is required to elucidate the issue.

Autophagy mediates the delivery of thrombogenic tissue factor to neutrophil extracellular traps in human sepsis.

BACKGROUND: Sepsis is associated with systemic inflammatory responses and induction of coagulation system. Neutrophil extracellular traps (NETs) constitute an antimicrobial mechanism, recently implicated in thrombosis via platelet entrapment and aggregation. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we demonstrate for the first time the localization of thrombogenic tissue factor (TF) in NETs released by neutrophils derived from patients with gram-negative sepsis and normal neutrophils treated with either serum from septic patients or inflammatory mediators involved in the pathogenesis of sepsis. Localization of TF in acidified autophagosomes was observed during this process, as indicated by positive LC3B and LysoTracker staining. Moreover, phosphatidylinositol 3-kinase inhibition with 3-MA or inhibition of endosomal acidification with bafilomycin A1 hindered the release of TF-bearing NETs. TF present in NETs induced thrombin generation in culture supernatants, which further resulted in protease activated receptor-1 signaling. CONCLUSIONS/SIGNIFICANCE: This study demonstrates the involvement of autophagic machinery in the extracellular delivery of TF in NETs and the subsequent activation of coagulation cascade, providing evidence for the implication of this process in coagulopathy and inflammatory response in sepsis.

Procalcitonin and procalcitonin kinetics for diagnosis and prognosis of intravascular catheter-related bloodstream infections in selected critically ill patients: a prospective observational study.

BACKGROUND: Procalcitonin (PCT) has emerged as a valuable marker of sepsis. The potential role of PCT in diagnosis and therapy monitoring of intravascular catheter-related bloodstream infections (CRBSI) in intensive care unit (ICU) is still unclear and was evaluated. METHODS: Forty-six patients were included in the study, provided they were free of infection upon admission and presented the first episode of suspected CRBSI during their ICU stay. Patients who had developed any other infection were excluded. PCT was measured daily during the ICU hospitalization. Primary endpoint was proven CRBSI. Therapy monitoring as according to infection control was also evaluated. RESULTS: Among the 46 patients, 26 were diagnosed with CRBSI. Median PCT on the day of infection suspicion (D0) was 7.70 and 0.10 ng/ml for patients with and without proven CRBSI, respectively (p < 0.001). The area under the curve (AUC) for PCT was 0.990 (95% CI; 0.972 - 1.000), whereas a cut-off value of 0.70 ng/ml provided sensitivity and specificity of 92.3 and 100% respectively. In contrast, the AUC for white blood cells (WBC) was 0.539 (95% CI; 0.369 - 0.709), and for C-reactive protein (CRP), 0.603 (95% CI; 0.438 - 0.768). PCT was the best predictor of proven infection. Moreover, an increase >0.20 ng/ml of PCT between the D0 and any of the 4 preceding days was associated with a positive predictive value exceeding 96%. PCT concentrations from the D2 to D6 after suspected infection tended to decrease in controlled patients, whereas remained stable in non-controlled subjects. A PCT concentration exceeding 1.5 ng/ml during D3 was associated with lack of responsiveness to therapy (p = 0.028). CONCLUSIONS: We suggest that PCT could be a helpful diagnostic and prognostic marker of CRBSI in critically ill patients. Both absolute values and variations should be considered.

Traumatic asphyxia due to blunt chest trauma: a case report and literature review.

INTRODUCTION: Crush asphyxia is different from positional asphyxia, as respiratory compromise in the latter is caused by splinting of the chest and/or diaphragm, thus preventing normal chest expansion. There are only a few cases or small case series of crush asphyxia in the literature, reporting usually poor outcomes. CASE PRESENTATION: We present the case of a 44-year-old Caucasian man who developed traumatic asphyxia with severe thoracic injury and mild brain edema after being crushed under heavy auto vehicle mechanical parts. He remained unconscious for an unknown time. The treatment included oropharyngeal intubation and mechanical ventilation, bilateral chest tube thoracostomies, treatment of brain edema and other supportive measures. Our patient's outcome was good. Traumatic asphyxia is generally under-reported and most authors apply supportive measures, while the final outcome seems to be dependent on the length of time of the chest compression and on the associated injuries. CONCLUSION: Treatment for traumatic asphyxia is mainly supportive with special attention to the re-establishment of adequate oxygenation and perfusion; treatment of the concomitant injuries might also affect the final outcome.

Temperature variability analysis using wavelets and multiscale entropy in patients with systemic inflammatory response syndrome, sepsis, and septic shock.

BACKGROUND: Even though temperature is a continuous quantitative variable, its measurement has been considered a snapshot of a process, indicating whether a patient is febrile or afebrile. Recently, other diagnostic techniques have been proposed for the association between different properties of the temperature curve with severity of illness in the Intensive Care Unit (ICU), based on complexity analysis of continuously monitored body temperature. In this study, we tried to assess temperature complexity in patients with systemic inflammation during a suspected ICU-acquired infection, by using wavelets transformation and multiscale entropy of temperature signals, in a cohort of mixed critically ill patients. METHODS: Twenty-two patients were enrolled in the study. In five, systemic inflammatory response syndrome (SIRS, group 1) developed, 10 had sepsis (group 2), and seven had septic shock (group 3). All temperature curves were studied during the first 24 hours of an inflammatory state. A wavelet transformation was applied, decomposing the signal in different frequency components (scales) that have been found to reflect neurogenic and metabolic inputs on temperature oscillations. Wavelet energy and entropy per different scales associated with complexity in specific frequency bands and multiscale entropy of the whole signal were calculated. Moreover, a clustering technique and a linear discriminant analysis (LDA) were applied for permitting pattern recognition in data sets and assessing diagnostic accuracy of different wavelet features among the three classes of patients. RESULTS: Statistically significant differences were found in wavelet entropy between patients with SIRS and groups 2 and 3, and in specific ultradian bands between SIRS and group 3, with decreased entropy in sepsis. Cluster analysis using wavelet features in specific bands revealed concrete clusters closely related with the groups in focus. LDA after wrapper-based feature selection was able to classify with an accuracy of more than 80% SIRS from the two sepsis groups, based on multiparametric patterns of entropy values in the very low frequencies and indicating reduced metabolic inputs on local thermoregulation, probably associated with extensive vasodilatation. CONCLUSIONS: We suggest that complexity analysis of temperature signals can assess inherent thermoregulatory dynamics during systemic inflammation and has increased discriminating value in patients with infectious versus noninfectious conditions, probably associated with severity of illness.

Study of multiparameter respiratory pattern complexity in surgical critically ill patients during weaning trials.

BACKGROUND: Separation from mechanical ventilation is a difficult task, whereas conventional predictive indices have not been proven accurate enough, so far. A few studies have explored changes of breathing pattern variability for weaning outcome prediction, with conflicting results. In this study, we tried to assess respiratory complexity during weaning trials, using different non-linear methods derived from theory of complex systems, in a cohort of surgical critically ill patients. RESULTS: Thirty two patients were enrolled in the study. There were 22 who passed and 10 who failed a weaning trial. Tidal volume and mean inspiratory flow were analyzed for 10 minutes during two phases: 1. pressure support (PS) ventilation (15-20 cm H2O) and 2. weaning trials with PS: 5 cm H2O. Sample entropy (SampEn), detrended fluctuation analysis (DFA) exponent, fractal dimension (FD) and largest lyapunov exponents (LLE) of the two respiratory parameters were computed in all patients and during the two phases of PS. Weaning failure patients exhibited significantly decreased respiratory pattern complexity, reflected in reduced sample entropy and lyapunov exponents and increased DFA exponents of respiratory flow time series, compared to weaning success subjects (p < 0.001). In addition, their changes were opposite between the two phases of the weaning trials. A new model including rapid shallow breathing index (RSBI), its product with airway occlusion pressure at 0.1 sec (P0.1), SampEn and LLE predicted better weaning outcome compared with RSBI, P0.1 and RSBI* P0.1 (conventional model, R(2) = 0.874 vs 0.643, p < 0.001). Areas under the curve were 0.916 vs 0.831, respectively (p < 0.05). CONCLUSIONS: We suggest that complexity analysis of respiratory signals can assess inherent breathing pattern dynamics and has increased prognostic impact upon weaning outcome in surgical patients.

Changes of heart and respiratory rate dynamics during weaning from mechanical ventilation: a study of physiologic complexity in surgical critically ill patients.

PURPOSE: The aim of the study was to investigate heart rate (HR) and respiratory rate (RR) complexity in patients with weaning failure or success, using both linear and nonlinear techniques. MATERIALS AND METHODS: Forty-two surgical patients were enrolled in the study. There were 24 who passed and 18 who failed a weaning trial. Signals were analyzed for 10 minutes during 2 phases: (1) pressure support (PS) ventilation (15-20 cm H(2)O) and (2) weaning trials with PS (5 cm H(2)O). Low- and high-frequency (LF, HF) components of HR signals, HR multiscale entropy (MSE), RR sample entropy, cross-sample entropy between cardiorespiratory signals, Poincaré plots, and α1 exponent were computed in all patients and during the 2 phases of PS. RESULTS: Weaning failure patients exhibited significantly decreased RR sample entropy, LF, HF, and α1 exponent, compared with weaning success subjects (P < .001). Their changes were opposite between the 2 phases, except for MSE that increased between and within groups (P < .001). A new model including rapid shallow breathing index (RSBI), α1 exponent, RR, and cross-sample entropies predicted better weaning outcome compared with RSBI, airway occlusion pressure at 0.1 second (P(0.1)), and RSBI × P(0.1) (conventional model, R(2) = 0.887 vs 0.463; P < .001). Areas under the curve were 0.92 vs 0.86, respectively (P < .005). CONCLUSIONS: We suggest that nonlinear analysis of cardiorespiratory dynamics has increased prognostic impact upon weaning outcome in surgical patients.

Relation of tricuspid annular displacement and tissue Doppler imaging velocities with duration of weaning in mechanically ventilated patients with acute pulmonary edema.

BACKGROUND: Liberation from the ventilator is a difficult task, whereas early echocardiographic indices of weaning readiness are still lacking. The aim of this study was to test whether tricuspid annular plane systolic excursion (TAPSE) and right ventricular (RV) systolic (Sm) and diastolic (Em & Am) tissue Doppler imaging (TDI) velocities are related with duration of weaning in mechanically ventilated patients with acute respiratory failure due to acute pulmonary edema (APE). METHODS: Detailed quantification of left and right ventricular systolic and diastolic function was performed at admission to the Intensive Care Unit by Doppler echocardiography, in a cohort of 32 mechanically ventilated patients with APE. TAPSE and RV TDI velocities were compared between patients with and without prolonged weaning (> or = or < 7 days from the first weaning trial respectively), whereas their association with duration of ventilation and left ventricular (LV) echo-derived indices was tested with multivariate linear and logistic regression analysis. RESULTS: Patients with prolonged weaning (n = 12) had decreased TAPSE (14.59 +/- 1.56 vs 19.13 +/- 2.59 mm), Sm (8.68 +/- 0.94 vs 11.62 +/- 1.77 cm/sec) and Em/Am ratio (0.98 +/- 0.80 vs 2.62 +/- 0.67, p <0.001 for all comparisons) and increased Epsilon/e' (11.31 +/- 1.02 vs 8.98 +/- 1.70, p <0.001) compared with subjects without prolonged weaning (n = 20). Logistic regression analysis revealed that TAPSE (R2 = 0.53, beta slope = 0.76, p < 0.001), Sm (R2 = 0.52, beta = 0.75, p < 0.001) and Em/Am (R2 = 0.57, beta = 0.32, p < 0.001) can predict length of weaning > or = 7 days. The above measures were also proven to correlate significantly with Epsilon/e' (r = -0.83 for TAPSE, r = -0.87 for Sm and r = -0.79 for Em/Am, p < 0.001 for all comparisons). CONCLUSIONS: We suggest that in mechanically ventilated patients with APE, low TAPSE and RV TDI velocities upon admission are associated with delayed liberation from mechanical ventilation, probably due to more severe LV heart failure.

Rhinosinusitis in the intensive care unit patients: a review of the possible underlying mechanisms and proposals for the investigation of their potential role in functional treatment interventions.

PURPOSE: Nosocomial rhinosinusitis (NS) is diagnosed in 2% to 26% of intubated patients and is associated with ventilator-associated pneumonia, septicemia, and fever of unknown etiology. The purpose of this study was to review the underlying pathogenetic mechanisms and the treatment options that derive from them. RESULT: The pathogenesis of NS seems to be mainly a combination of the failure of the local defenses and self-clearance mechanisms and the development of topical factors, which favor the colonization of the nasal and antral cavities with pathogens. The systemic administration of antibiotics, which are the current treatment of NS, have a limited, if any, effect on any of the above pathophysiologic mechanisms. However, the review of the literature demonstrates that the research on functionally orientated treatment options has been limited to the effect of orotracheal vs nasotracheal intubation. There are no clinical trials investigating the effect, which combinations of pathophysiology-based measures may have on the prevalence and treatment of NS and ventilator-associated pneumonia. CONCLUSION: An update of the pathogenetic mechanisms demonstrates that the prevention and treatment of nosocomial rhinosinusitis may expand well beyond the systemic administration of antibiotics.

Biosignal analysis techniques for weaning outcome assessment.

Discontinuation of mechanical ventilation in critically ill patients is a challenging task and involves a careful weighting of the benefits of early extubation and the risks of premature spontaneous breathing trial. Recently, apart from studying different physiological variables by means of descriptive statistical tests, breathing pattern variability analysis has been performed for the assessment of weaning readiness. A limited number of clinical studies implementing different weaning protocols in heterogeneous groups of patients and using a variable set of signal processing techniques have appeared in the critical care literature, with varying results. The purpose of this review article is 3-fold: (1) to describe the different signal processing techniques being implemented for the assessment of weaning readiness, (2) to provide insight into the pathophysiological mechanisms that may govern breath-to-breath variability/complexity in health and disease, and (3) to present results from the critical care literature derived from the application of biosignal analysis tools for the identification of possible weaning indices.

Negative-pressure acute tracheobronchial hemorrhage and pulmonary edema.

Negative-pressure pulmonary edema is a well-known complication of an acute upper airway obstruction, which may rarely present as acute alveolar hemorrhage in cases of severe capillary stress failure. Hemorrhage from the central airways has also been reported as a rare manifestation of acute tracheobronchial injury, associated with severe disruption of the bronchial vasculature due to highly negative inspiratory pressure. In this clinical report, we describe a case of both acute tracheobronchial and alveolar hemorrhage in a young man, occurring immediately after extubation due to laryngospasm, diagnosed by bronchoscopy with bronchoalveolar lavage (BAL), measurement of the pulmonary edema fluid/plasma protein ratio, and by thoracic computed tomography (CT) scan. We propose that the patient experienced severe postobstructive negative-pressure pulmonary edema, related to increased permeability of the alveolar capillary membrane and a parallel loss of integrity of the bronchial vascular network. Our findings suggest that both changes in the bronchial circulation and mechanical stress failure of the more distal alveolar-capillary system may be induced by severe and acute upper-airway obstruction.