Impact of hemoperfusion with polymyxin B added to hemofiltration in patients with endotoxic shock: a case-control study.

BACKGROUND: Septic shock is a leading cause of death in critical patients. In patients with gram-negative septic shock, hemoperfusion with polymyxin B aims to remove endotoxins from plasma. We analyzed the clinical and biological response to hemoperfusion in patients with septic shock and acute kidney injury. METHODS: This prospective case-control study in the medical-surgical intensive care unit of a university hospital included consecutive adults patients with septic shock and suspected gram-negative bacteria infection with elevated plasma endotoxin activity (EAA > 0.6 EU/ml) and acute kidney injury requiring continuous renal replacement therapy (CRRT). At onset of septic shock, half underwent CRRT plus hemoperfusion with polymyxin B for two hours a day during two consecutive days (hemoperfusion group) and half received only CRRT (control group). We measured clinical, physiological, and biological parameters (EAA, C-reactive protein, procalcitonin, and cytokines) daily during the first 5 days. RESULTS: We included 18 patients (male, 33%; mean age, 67.5; mean SOFA score, 11.3). Abdominal infections predominated (50% had peritonitis). At the beginning of CRRT, RIFLE classification was "failure" for 72% and "injury" for 28%. Baseline characteristics did not differ between groups. Patients in the hemoperfusion group required longer mechanical ventilation (12.4 vs. 9.4 days, p = 0.03) and CRRT (8.5 vs. 6 days, p = 0.01) than in the control group. Noradrenaline doses, lactate, procalcitonin, and C-reactive protein decreased in both groups. At day 5, EAA was significantly lower in the hemoperfusion group (0.58 EU/ml vs. 0.73 EU/ml in controls, p = 0.03). There were no significant differences between groups in other biomarkers or ICU mortality (33.3% in the treatment group vs. 44.4% in the control group, p = 0.5). No adverse effects of hemoperfusion were observed. CONCLUSIONS: Hemoperfusion with polymyxin B added to CRRT resulted in faster decrease in endotoxin levels, but we observed no improvements in clinical, physiological, or biological parameters.

Biomarkers kinetics in the assessment of ventilator-associated pneumonia response to antibiotics - results from the BioVAP study.

PURPOSE: Our aim was to evaluate the role of biomarker kinetics in the assessment of ventilator-associated pneumonia (VAP) response to antibiotics. MATERIALS AND METHODS: We performed a prospective, multicenter, observational study to evaluate in 37 microbiologically documented VAP, the kinetics of C-reactive protein (CRP), procalcitonin (PCT), mid-region fragment of pro-adrenomedullin (MR-proADM). The kinetics of each variable, from day 1 to 6 of therapy, was assessed with a time dependent analysis comparing survivors and non-survivors. RESULTS: During the study period kinetics of CRP as well as its relative changes, CRP-ratio, was significantly different between survivors and non-survivors (p=0.026 and p=0.005, respectively). On day 4 of antibiotic therapy, CRP of survivors was 47% of the initial value while it was 96% in non-survivors. The kinetics of other studied variables did not distinguish between survivors and non-survivors. In survivors the bacterial load also decreased markedly. Adequate initial antibiotic therapy was associated with lower mortality (p=0.025) and faster CRP decrease (p=0.029). CONCLUSIONS: C-reactive protein kinetics can be used to identify VAP patients with poor outcome as soon as four days after the initiation of treatment. (Trial registration - NCT02078999; registered 3 August 2012).

Biomarker kinetics in the prediction of VAP diagnosis: results from the BioVAP study.

BACKGROUND: Prediction of diagnosis of ventilator-associated pneumonia (VAP) remains difficult. Our aim was to assess the value of biomarker kinetics in VAP prediction. METHODS: We performed a prospective, multicenter, observational study to evaluate predictive accuracy of biomarker kinetics, namely C-reactive protein (CRP), procalcitonin (PCT), mid-region fragment of pro-adrenomedullin (MR-proADM), for VAP management in 211 patients receiving mechanical ventilation for >72 h. For the present analysis, we assessed all (N = 138) mechanically ventilated patients without an infection at admission. The kinetics of each variable, from day 1 to day 6 of mechanical ventilation, was assessed with each variable's slopes (rate of biomarker change per day), highest level and maximum amplitude of variation (Δ (max)). RESULTS: A total of 35 patients (25.4 %) developed a VAP and were compared with 70 non-infected controls (50.7 %). We excluded 33 patients (23.9 %) who developed a non-VAP nosocomial infection. Among the studied biomarkers, CRP and CRP ratio showed the best performance in VAP prediction. The slope of CRP change over time (adjusted odds ratio [aOR] 1.624, confidence interval [CI]95% [1.206, 2.189], p = 0.001), the highest CRP ratio concentration (aOR 1.202, CI95% [1.061, 1.363], p = 0.004) and Δ (max) CRP (aOR 1.139, CI95% [1.039, 1.248], p = 0.006), during the first 6 days of mechanical ventilation, were all significantly associated with VAP development. Both PCT and MR-proADM showed a poor predictive performance as well as temperature and white cell count. CONCLUSIONS: Our results suggest that in patients under mechanical ventilation, daily CRP monitoring was useful in VAP prediction. Trial registration NCT02078999.

Study of the prevalence of familial autoimmune myasthenia gravis in a Spanish cohort.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease caused by a failure of neuromuscular transmission. Familial clustering has been reported despiteMG usually manifesting as a sporadic condition presumed not to be inherited. Our study investigated the prevalence of FAMG in a Spanish cohort, characterizing their phenotype,antibody titres and thymus findings. MATERIAL/METHODS: We investigated the presence of familial cases in 462 MG patients, characterizing by age and MGFA class at debut, quantitative MG score, antibody titres, MGFA post-intervention status and thymus pathology. RESULTS: Sixteen cases from8 unrelated pedigrees were identified. The prevalence of FAMG caseswas 3.46%.Mean age at onset was 57.8 ± 17.4 years (range=23­82). Distribution at debut was: 6 ocular, 4 IIa, 4IIb, 1 IIIa and 1 IIIb. Thymoma was identified in two of the 7 thymectomized individuals. CONCLUSIONS: The prevalence of FAMG in Spain is similar to other populations. Post-intervention status did not differ from sporadic autoimmune MG. As in other neuromuscular disorders, phenotype and inheritance heterogeneity are present in FAMG. In addition to the interfamilial heterogeneity observed, members of the same family affected with FAMG may even present different ages of onset, severity and thymus involvement. Further studies are necessary to clarify the role of genetic risk factors in this form of autoimmune MG.

Operational evaluation of the earlobe arterialized blood collector in critically ill patients.

BACKGROUND: The new Earlobe Arterialized Blood Collector (EABC®) is a minimally invasive prototype system able to perform capillary blood collection from the earlobe (EL) with minimal training and risk. This system could improve medical emergency management in extreme environments. Consequently, a prospective validation study was designed to evaluate operational performance of the EABC® in a cohort of critically ill patients. METHODS: Arterialized capillary blood was sampled from the EL of 55 invasively ventilated patients using the EABC® following a validated procedure. Operational characteristics such as the number of cuts and cartridges required, sampling failure/success ratio, bleeding complications, storage requirements and other auxiliary aspects were recorded. Result turnaround laboratory times (TAT) were compared with published references. RESULTS: Blood collection was as easily performed on one earlobe as the other. Twenty-six minutes (mean 25.8; SD = 3.8) were required to obtain results, 15 min for patient preparation (mean 15.3; SD = 2.6) + 11 min for sampling and analysis (mean 11.4; SD = 2.1), which is similar to published hospital reference laboratory TAT. The average number of cartridges required was 1.3 (1-3; mode = 1) with the mean number of cut attempts being 1.2 (1-4; mode = 1). Problems/difficulties occurred in 59% of cases but were mainly attributed to patient's demographic characteristics, with only 10% attributable to the collector (superficial cut, blood leak, collector misalignment and obstructed vision). Haemostasis was quickly achieved with minimum complications. Storage of the complete sampling kit required a 300 × 300 × 300 mm box. Two 9-V batteries were used during the 2-year study period. CONCLUSIONS: The new EABC® system concept is safe, fast and easy to use. Observed problems/difficulties are easily amendable with certain design modifications. Definitive versions of the prototype have the potential for significant benefits for isolated and extreme environments in medicine.

Earlobe arterialized capillary blood gas analysis in the intensive care unit: a pilot study.

BACKGROUND: Earlobe arterialized capillary blood gas analysis can be used to estimate arterial gas content and may be suitable for diagnosis and management of critically ill patients. However, its utility and applicability in the ICU setting remains unexplored. METHODS: A prospective observational validation study was designed to evaluate this technique in a cohort of mechanically ventilated adult critically ill patients admitted to a polyvalent ICU. Precision and agreement between capillary gas measures and arterial references was examined. Acute Respiratory Distress Syndrome (ARDS) diagnosis capabilities with the proposed technique were also evaluated. Finally, factors associated with sampling failure were explored. RESULTS: Fifty-five patients were included into this study. Precision of capillary samples was high (Coefficient of Variation PO2 = 9.8%, PCO2 = 7.7%, pH = 0.3%). PO2 measures showed insufficient agreement levels (Concordance Correlation Coefficient = 0.45; bias = 12 mmHg; percentage of error = 19.3%), whereas better agreement was observed for PCO2 and pH (Concordance Correlation Coefficient = 0.94 and 0.93 respectively; depreciable bias; percentage of error 11.4% and 0.5% respectively). The sensitivity and specificity for diagnosing ARDS were 100% and 92.3% using capillary gasometric measures. Sampling was unsuccessful in 43.6% of cases due to insufficient blood flow. Age > 65 years was independently associated with failure (odds ratio = 1.6), however hemodynamic failure and norepinephrine treatment were also influencing factors. CONCLUSIONS: Earlobe capillary blood gas analysis is precise and can be useful for detecting extreme gasometrical values. Diagnosis of ARDS can be done accurately using capillary measurements. Although this technique may be insufficient for precise management of patients in the ICU, it has the potential for important benefits in the acute phase of various critical conditions and in other critical care arenas, such as in emergency medicine, advanced medical transport and pre-hospital critical care.

Near-infrared spectroscopy StO2 monitoring to assess the therapeutic effect of drotrecogin alfa (activated) on microcirculation in patients with severe sepsis or septic shock.

BACKGROUND: Sepsis is a leading cause of death despite appropriate management. There is increasing evidence that microcirculatory alterations might persist independently from macrohemodynamic improvement and are related to clinical evolution. Future efforts need to be directed towards microperfusion monitoring and treatment. This study explored the utility of thenar muscle oxygen saturation (StO2) and its changes during a transient vascular occlusion test (VOT) to measure the microcirculatory response to drotrecogin alfa (activated) (DrotAA) in septic patients. METHODS: A prospective, observational study was performed in three general intensive care units at three university hospitals. We studied 58 patients with recent onset of severe sepsis or septic shock and at least two organ dysfunctions. Thirty-two patients were treated with DrotAA and 26 were not treated because of formal contraindication. StO2 was monitored using near-infrared spectroscopy (NIRS), and VOT was performed to obtain deoxygenation (DeOx) and reoxygenation (ReOx) slopes. Measurements were obtained before DrotAA was started and were repeated daily for a 96-hour period. RESULTS: Patients' characteristics, outcome, severity, and baseline values of StO2, DeOx, and ReOx did not differ between groups. Treated patients significantly improved DeOx and ReOx values over time, whereas control patients did not. In treated patients, ReOx improvements were correlated to norepinephrine dose reductions. Early clinical response (SOFA improvement after 48 hours of treatment) was not associated to changes in VOT-derived slopes. In the treated group, the relative improvement of DeOx within 48 hours was able to predict mortality (AUC 0.91, p < 0.01). CONCLUSIONS: In patients with severe sepsis or septic shock, DrotAA infusion was associated with improvement in regional tissue oxygenation. The degree of DeOx amelioration after 2 days in treated patients predicted mortality with high sensitivity and specificity. Thus, StO2 derived variables might be useful to evaluate the microcirculatory response to treatment of septic shock.

Assessment of the inflammatory effect of low-dose oxygen in mechanically ventilated patients.

PURPOSE: Although low doses of oxygen (FiO2 <0.50) are considered nontoxic, recent studies have shown that even lower doses increase pulmonary inflammatory mediators. We aimed to evaluate the acute effects of reducing FiO2 on pulmonary inflammation in mechanically ventilated patients without respiratory failure. METHODS: This study was a prospective, single-center crossover study in a medical/surgical intensive care unit at a university hospital. Hemodynamically stable patients under mechanical ventilation for >24 h without severe respiratory failure (PaO2/FiO2 >250). A basal FiO2 of 0.40 was reduced to 0.21 provided SpO2 remained higher than 90 %. Patients who could not tolerate the reduction in FiO2 to 0.21 were excluded. RESULTS: We screened 40 patients, but only 28 (70 %) tolerated FiO2 0.21. We measured common clinical variables and inflammatory mediators in plasma and in exhaled breath condensate (EBC) at the end of three 4-h periods: (1) basal (FiO2 0.40), (2) after FiO2 reduction to 0.21, and (3) after returning FiO2 0.40. We used one-way ANOVA for repeated measurements with FiO2 as the grouping variable. Median values of inflammatory mediators in EBC showed nonsignificant changes among the three periods: NO2 + NO3 17.1, 14.1 and 11.0 µmol/L (p = 0.2), and 8-isoprostane 4.4, 8.2 and 5.3 pg/ml (p = 0.6) for the three periods, respectively. Plasma levels also showed nonsignificant changes during the period of the study: NO2 + NO3 12.6, 16.3 and 15.0 µmol/L (p = 0.9), TNFα 13.5, 18.0 and 14.5 pg/ml (p = 0.8), IL-4 12.9, 18.7 and 23.9 pg/ml (p = 0.1), IL-6 50.9, 35.1 and 28.3 pg/ml (p = 0.6), and IL-10 15.2, 22.2 and 22.2 pg/ml (p = 0.7) for the three periods, respectively. CONCLUSION: FiO2 0.40 in mechanically ventilated patients without severe respiratory failure did not increase systemic or pulmonary inflammation.

Thenar oxygen saturation measured by near infrared spectroscopy as a noninvasive predictor of low central venous oxygen saturation in septic patients.

OBJECTIVE: To validate thenar oxygen saturation (StO(2)) measured by near-infrared spectroscopy (NIRS) as a noninvasive estimation of central venous saturation (ScvO(2)) in septic patients. DESIGN: Prospective observational study. SETTING: A 26-bed medical-surgical intensive care unit at a university-affiliated hospital. PATIENTS: Patients consecutively admitted to the ICU in the early phase of severe sepsis and septic shock, after normalization of blood pressure with fluids and/or vasoactive drugs. MEASUREMENTS: We recorded demographic data, severity score, hemodynamic data, and blood lactate, as well as ScvO(2), and StO(2) measured simultaneously on inclusion. Patients were divided into two groups according to ScvO(2) values: group A, with ScvO(2) < 70%, and group B, with ScvO(2) > or = 70%. RESULTS: Forty patients were studied. StO(2) was significantly lower in group A than in group B (74.7 +/- 13.0 vs. 83.3 +/- 6.2, P 0.018). No differences in age, severity score, hemodynamics, vasoactive drugs, or lactate were found between groups. Simultaneously measured ScvO(2) and StO(2) showed a significant Pearson correlation (r = 0.39, P 0.017). For a StO(2) value of 75%, sensitivity was 0.44, specificity 0.93, positive predictive value 0.92, and negative predictive value 0.52 for detecting ScvO(2) values lower than 70%. CONCLUSIONS: StO(2) correlates with ScvO(2) in normotensive patients with severe sepsis or septic shock. We propose a StO(2) cut-off value of 75% as a specific, rapid, noninvasive first step for detecting patients with low ScvO(2) values. Further studies are necessary to analyze the role of noninvasive StO(2) measurement in future resuscitation algorithms.

Ward mortality in patients discharged from the ICU with tracheostomy may depend on patient's vulnerability.

OBJECTIVE: To determine the effect of discharge from the ICU with a tracheostomy tube on ward mortality and its relation to patient vulnerability. DESIGN AND SETTING: Retrospective single-center cohort study. METHODS: Database (2003-2006) review of patients undergoing mechanical ventilation (MV) > 24 h and discharged from the ICU with or without tracheostomy tube in place and followed up to hospital discharge or death. We recorded clinical characteristics, complications, major ICU procedures, subjective prognosis at ICU discharge (Sabadell score), and hospital outcome. Factors associated with ward mortality were analyzed by multiple logistic regression. RESULTS: From 3,065 patients admitted to the ICU, 1,502 needed MV > 24 h. Only 936 patients (62%) survived the ICU and were transferred to the ward; of these, 130 (13.9%) had a tracheostomy tube in place. Ward mortality was higher in patients with a tracheostomy tube in place than in those without (26 vs. 7%, P < 0.001). Increased ward mortality among cannulated patients was seen only in those with intermediate Sabadell score (24 vs. 9% in score 1, P = 0.02, and 38 vs. 24% in score 2, P = 0.06), but not in the "good prognosis" (2 vs. 2%, score 0) and "expected to die in hospital" (80 vs. 75%, score 3) groups. Multivariate analysis found three factors associated with ward mortality: age, tracheostomy tube in place, and Sabadell score. CONCLUSION: Lack of tracheostomy decannulation in the ICU appears to be associated with ward mortality, but only in the group with a Sabadell score of 1.