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.

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.

Association of transcranial Doppler blood flow velocity slow waves with delayed cerebral ischemia in patients suffering from subarachnoid hemorrhage: a retrospective study.

BACKGROUND: Cerebral vasospasm (VS) and delayed cerebral ischemia (DCI) constitute major complications following subarachnoid hemorrhage (SAH). A few studies have examined the relationship between different indices of cerebrovascular dynamics with the occurrence of VS. However, their potential association with the development of DCI remains elusive. In this study, we investigated the pattern of changes of different transcranial Doppler (TCD)-derived indices of cerebrovascular dynamics during vasospasm in patients suffering from subarachnoid hemorrhage, dichotomized by the presence of delayed cerebral ischemia. METHODS: A retrospective analysis was performed using recordings from 32 SAH patients, diagnosed with VS. Patients were divided in two groups, depending on development of DCI. Magnitude of slow waves (SWs) of cerebral blood flow velocity (CBFV) was measured. Cerebral autoregulation was estimated using the moving correlation coefficient Mxa. Cerebral arterial time constant (tau) was expressed as the product of resistance and compliance. Complexity of CBFV was estimated through measurement of sample entropy (SampEn). RESULTS: In the whole population (N = 32), magnitude of SWs of ipsilateral to VS side CBFV was higher during vasospasm (4.15 ± 1.55 vs before: 2.86 ± 1.21 cm/s, p < 0.001). Ipsilateral SWs of CBFV before VS had higher magnitude in DCI group (N = 19, p < 0.001) and were strongly predictive of DCI, with area under the curve (AUC) = 0.745 (p = 0.02). Vasospasm caused a non-significant shortening of ipsilateral values of tau and increase in SampEn in all patients related to pre-VS measurements, as well as an insignificant increase of Mxa in DCI related to non-DCI group (N = 13). CONCLUSIONS: In patients suffering from subarachnoid hemorrhage, TCD-detected VS was associated with higher ipsilateral CBFV SWs, related to pre-VS measurements. Higher CBFV SWs before VS were significantly predictive of delayed cerebral ischemia.

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.

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.

Melatonin and cortisol exhibit different circadian rhythm profiles during septic shock depending on timing of onset: a prospective observational study.

BACKGROUND: Septic shock has been found to disrupt circadian rhythms. Moreover, timing of onset has been associated with different circadian profiles in experimental studies. RESULTS: In this prospective study, we enrolled 26 patients divided into two groups: Group A (N = 15) included subjects who had septic shock at the time of ICU admission and Group B (N = 11) included patients who developed septic shock during ICU admission. 6-Sulfatoxymelatonin (aMT6s) and cortisol levels were measured in urine samples every 4 h over a 24-h period. Two sets of samples were taken from Group A (entry/septic shock and exit) and three sets from Group B (entry, septic shock and exit). Mean, amplitude that is the difference between peak and mean values, as well as peak time, were estimated for both aMT6s and cortisol. In Group A, amplitude of aMT6s upon entry (septic shock) was reduced in relation to exit (437.2 ± 309.2 vs. 674.1 ± 657.6 ng/4 h, p < 0.05). Peak time occurred earlier (10:00 p.m. vs. 07:00 a.m, p < 0.05) and correlated with higher APACHE II score and longer ICU stay. In Group B, aMT6s mean values were significantly increased during septic shock (2492.2 ± 1709.1 ng/4 h) compared to both entry (895.4 ± 715.5 ng/4 h) and exit (1308.6 ± 1214.4 ng/4 h, p < 0.05 for all comparisons). Amplitude of aMT6s was also elevated during septic shock (794.8 ± 431.8 ng/4 h) in relation to entry (293.1 ± 275.9 ng/4 h, p < 0.05). Regarding cortisol rhythm in Group A, during septic shock amplitude was increased compared to exit (13.3 ± 31 ng/4 h vs. 8.7 ± 21.2 ng/4 h p < 0.05) and correlated with reduced hospital length of stay. In Group B, cortisol mean values and amplitude during septic shock (10 ± 5.3 and 3 ± 1.8 ng/4 h, respectively) were significantly reduced compared to both entry (30 ± 57.9 and 12.3 ± 27.3 ng/4 h) and exit (14.4 ± 20.7 and 6.6 ± 8.7 ng/4 h, p < 0.05 for all comparisons) and correlated with higher SOFA score and longer ICU and hospital stay. CONCLUSIONS: Septic shock induced inverse changes of aMT6s and cortisol circadian rhythm profiles both within and between different groups of patients, depending on timing of onset. Reduced rhythmicity was correlated with severity of disease and longer ICU stay.

Investigation of altered heart rate variability, nonlinear properties of heart rate signals, and organ dysfunction longitudinally over time in intensive care unit patients.

PURPOSE: To investigate longitudinally over time heart rate dynamics and relation with mortality and organ dysfunction alterations in patients admitted to a multidisciplinary intensive care unit. METHODS: Data from 53 patients were used, with heart rate recorded from monitors and analyzed on a daily basis (every morning) for 600 seconds and sampling rate at 250 Hz, from admission to the intensive care unit until final discharge from the unit. Variance, which is a measure of heart rate variability; exponent alpha2; and approximate entropy (ApEn), which assess long-range correlations and periodicity within a signal, respectively; were measured and compared with every day Sequential Organ Failure Assessment Score (SOFA) and mortality. RESULTS: Nonsurvivors had lower ApEn mean (greater periodicity in their signals) and minimum values compared to survivors (0.53 +/- 0.25 vs 0.62 +/- 0.23, P = .04; 0.24 +/- 0.23 vs 0.48 +/- 0.23, P = .01, respectively). Patients in better conditions with SOFA of less than 7 (mean value) had higher variance and ApEn (more variable, less periodic signals) than those with SOFA of 7 or higher (0.47 +/- 0.51 vs 0.10 +/- 0.65, P < .001; 0.67 +/- 0.28 vs 0.49 +/- 0.24, P < .001, respectively). The alpha2 exponent and variance were correlated with length of stay (r = 0.55, P = .02, and r = 0.53, P = .02, respectively) and minimum ApEn with mortality (r = 0.41, P = .01). CONCLUSIONS: Loss of variability and increase in periodicity in heart rate of critically ill patients are linked with parallel deterioration of organ dysfunction and high mortality.

Intracardiac origin of heart rate variability, pacemaker funny current and their possible association with critical illness.

Heart rate variability (HRV) is an indirect estimator of autonomic modulation of heart rate and is considered a risk marker in critical illness, particularly in heart failure and severe sepsis. A reduced HRV has been found in critically ill patients and has been associated with neuro-autonomic uncoupling or decreased baroreflex sensitivity. However, results from human and animal experimental studies indicate that intracardiac mechanisms might also be responsible for interbeat fluctuations. These studies have demonstrated that different membrane channel proteins and especially the so-called 'funny' current (If), an hyperpolarization-activated, inward current that drives diastolic depolarization resulting in spontaneous activity in cardiac pacemaker cells, are altered during critical illness. Furthermore, membrane channels kinetics seem to have significant impact upon HRV, whose early decrease might reflect a cellular metabolic stress. In this review article we present research findings regarding intracardiac origin of HRV, at the cellular level and in both isolated sinoatrial node and whole ex vivo heart preparations. In addition, we will review results from various experimental studies that support the interrelation between If and HRV during endotoxemia. We suggest that reduced HRV during sepsis could also be associated with altered pacemaker cell membrane properties, due to ionic current remodeling.

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 heart rate variability to serum levels of C-reactive protein, interleukin 6, and 10 in patients with sepsis and septic shock.

PURPOSE: The aim of the study was to investigate possible associations between different heart rate variability (HRV) indices and various biomarkers of inflammation in 45 septic patients. MATERIALS AND METHODS: We daily assessed HRV in the time domain (SD of RR intervals [SDNN]), frequency domain (low [LF], high frequency [HF], LF/HF as an indicator of sympathovagal balance); the 2 values of SD (SD1, SD2) from the Poincaré plot; and measured C-reactive protein, interleukin 6, and interleukin 10 serum levels in patients with sepsis and mean Sequential Organ Failure Assessment score (SOFA) 10 or lower (n = 25) and septic shock (SOFA > 10, n = 20) for 6 days. RESULTS: C-reactive protein exhibited significant negative correlations with LF (r = -0.78), LF/HF (r = -0.61), and SDNN (r = -0.79) and positive correlations with HF (r = 0.80) and SD1/SD2 (r = 0.66), whereas interleukin 10 was positively correlated with HF (r = 0.71) and negatively with LF (r = -0.89) and LF/HF (r = -0.66) in septic shock patients (P < .05 for all comparisons). Standard deviation of RR intervals and HF proved to be independent predictors of the severity of disease (beta slope [B] = -1.091; P = .013; 95% confidence interval [CI], -1.43 to -0.74, and B = 0.78; P = .022; 95% CI, 0.21-1.35, respectively). CONCLUSIONS: Our data suggest that low HRV and sympathovagal balance during septic shock are associated with both an increased hyperinflammatory and antiinflammatory response.

A step-by-step diagnosis of exclusion in a twin pregnancy with acute respiratory failure due to non-fatal amniotic fluid embolism: a case report.

INTRODUCTION: Respiratory failure may develop during the later stages of pregnancy and is usually associated with tocolysis or other co-existing conditions such as pneumonia, sepsis, pre-eclampsia or amniotic fluid embolism syndrome. CASE PRESENTATION: We present the case of a 34-year-old healthy woman with a twin pregnancy at 31 weeks and 6 days who experienced acute respiratory failure, a few hours after administration of tocolysis (ritodrine), due to preterm premature rupture of the membranes. Her chest discomfort was significantly ameliorated after the ritodrine infusion was stopped and a Cesarean section was performed 48 hours later under spinal anesthesia; however, 2 hours after surgery she developed severe hypoxemia, hypotension, fever and mild coagulopathy. The patient was intubated and transferred to the intensive care unit where she made a quick and uneventful recovery within 3 days. As there was no evidence for drug- or infection-related thromboembolic or myocardial causes of respiratory failure, we conclude that our patient experienced a rare type of non-fatal amniotic fluid embolism. CONCLUSION: In spite of the lack of solid scientific support for our diagnosis, we conclude that our patient suffered an uncommon type of amniotic fluid embolism syndrome and we believe that this report highlights the need for extreme vigilance and a high index of suspicion for such a diagnosis in any pregnant individual.