Promotion of physical activity after hospitalization for COPD exacerbation: A randomized control trial.

BACKGROUND AND OBJECTIVE: Physical activity worsens during exacerbations of chronic obstructive pulmonary disease (COPD) and notably after hospitalizations. Pedometer-based interventions are useful to increase physical activity in stable patients with COPD. However, there is little information concerning the implementation of such programs following severe exacerbation. This study assessed the efficacy of a physical activity program after hospitalization for a COPD exacerbation. METHODS: We performed a prospective, 12-week, parallel group, assessor-blinded, randomized control trial in COPD patients hospitalized for an exacerbation. After discharge, physical activity and other secondary variables were assessed. Patients were allocated (1:1) to a physical activity promotion program (intervention group, IG) or usual care (control group, CG). Based on a motivational interview and accelerometer physical activity assessment, a patient-tailored, pedometer-based, progressive and target-driven program was designed. Linear mixed effect models were used to analyse between-group differences. RESULTS: Forty-six out of 61 patients recruited were randomized and 43 (IG = 20, CG = 23) completed the study. In-hospital and baseline characteristics were similar in both groups. After 12 weeks of intervention, the mean steps difference between groups was 2093 steps/day, p = 0.018, 95% CI 376-4012, favouring the IG. Only the IG significantly increased the number of steps/day compared to baseline (mean difference [95% CI] 2932 [1069-4795] steps; p = 0.004). There were no other between-group differences. CONCLUSION: After hospitalization for a COPD exacerbation, a patient-tailored physical activity program based on a motivational interview and the use of pedometers, with progressive and customized targets, improved the number of steps/day.

Structural and Lattice-Dynamical Properties of Tb2O3 under Compression: A Comparative Study with Rare Earth and Related Sesquioxides.

We report a joint experimental and theoretical investigation of the high pressure structural and vibrational properties of terbium sesquioxide (Tb2O3). Powder X-ray diffraction and Raman scattering measurements show that cubic Ia3̅ (C-type) Tb2O3 undergoes two phase transitions up to 25 GPa. We observe a first irreversible reconstructive transition to the monoclinic C2/m (B-type) phase at ∼7 GPa and a subsequent reversible displacive transition from the monoclinic to the trigonal P3̅m1 (A-type) phase at ∼12 GPa. Thus, Tb2O3 is found to follow the well-known C → B → A phase transition sequence found in other cubic rare earth sesquioxides with cations of larger atomic mass than Tb. Our ab initio theoretical calculations predict phase transition pressures and bulk moduli for the three phases in rather good agreement with experimental results. Moreover, Raman-active modes of the three phases have been monitored as a function of pressure, while lattice-dynamics calculations have allowed us to confirm the assignment of the experimental phonon modes in the C- and A-type phases as well as to make a tentative assignment of the symmetry of most vibrational modes in the B-type phase. Finally, we extract the bulk moduli and the Raman-active mode frequencies together with their pressure coefficients for the three phases of Tb2O3. These results are thoroughly compared and discussed in relation to those reported for rare earth and other related sesquioxides as well as with new calculations for selected sesquioxides. It is concluded that the evolution of the volume and bulk modulus of all the three phases of these technologically relevant compounds exhibit a nearly linear trend with respect to the third power of the ionic radii of the cations and that the values of the bulk moduli for the three phases depend on the filling of the f orbitals.

Orpiment under compression: metavalent bonding at high pressure.

We report a joint experimental and theoretical study of the structural, vibrational, and electronic properties of layered monoclinic arsenic sulfide crystals (α-As2S3), aka mineral orpiment, under compression. X-ray diffraction and Raman scattering measurements performed on orpiment samples at high pressure and combined with ab initio calculations have allowed us to determine the equation of state and the tentative assignment of the symmetry of many Raman-active modes of orpiment. From our results, we conclude that no first-order phase transition occurs up to 25 GPa at room temperature; however, compression leads to an isostructural phase transition above 20 GPa. In fact, the As coordination increases from threefold at room pressure to more than fivefold above 20 GPa. This increase in coordination can be understood as the transformation from a solid with covalent bonding to a solid with metavalent bonding at high pressure, which results in a progressive decrease of the electronic and optical bandgap, an increase of the dielectric tensor components and Born effective charges, and a considerable softening of many high-frequency optical modes with increasing pressure. Moreover, we propose that the formation of metavalent bonding at high pressures may also explain the behavior of other group-15 sesquichalcogenides under compression. In fact, our results suggest that group-15 sesquichalcogenides either show metavalent bonding at room pressure or undergo a transition from p-type covalent bonding at room pressure towards metavalent bonding at high pressure, as a precursor towards metallic bonding at very high pressure.

High-Pressure High-Temperature Stability and Thermal Equation of State of Zircon-Type Erbium Vanadate.

The zircon to scheelite phase boundary of ErVO4 has been studied by high-pressure and high-temperature powder and single-crystal X-ray diffraction. This study has allowed us to delimit the best synthesis conditions of its scheelite-type phase, determine the ambient-temperature equation of state of the zircon and scheelite-type structures, and obtain the thermal equation of state of the zircon-type polymorph. The results obtained with powder samples indicate that zircon-type ErVO4 transforms to scheelite at 8.2 GPa and 293 K and at 7.5 GPa and 693 K. The analyses yield bulk moduli K0 of 158(13) GPa for the zircon phase and 158(17) GPa for the scheelite phase, with a temperature derivative of d K0/d T = -[3.8(2)] × 10-3 GPa K-1 and a volumetric thermal expansion of α0 = [0.9(2)] × 10-5 K-1 for the zircon phase according to the Berman model. The results are compared with those of other zircon-type vanadates, raising the need for careful experiments with highly crystalline scheelite to obtain reliable bulk moduli of this phase. Finally, we have performed single-crystal diffraction experiments from 110 to 395 K, and the obtained volumetric thermal expansion (α0) for zircon-type ErVO4 in the 300-395 K range is [1.4(2)] × 10-5 K-1, in good agreement with previous data and with our experimental value given from the thermal equation of state fit within the limits of uncertainty.

Prophylaxis Versus Treatment Use of Laxative for Paralysis of Lower Gastrointestinal Tract in Critically Ill Patients.

GOALS: To evaluate the prevalence of lower gastrointestinal tract paralysis and to compare the success to achieve defecation between treatment and prophylaxis strategies. BACKGROUND: Laxatives use is commonly the first-level measure to achieve defecation in critically ill patients with lower gastrointestinal tract paralysis. Studies comparing prophylaxis versus treatment of lower gastrointestinal tract paralysis have not been performed yet. STUDY: We designed 3 sequential phases of 4 months each: observational phase, treatment phase, and prophylaxis phase. First-level measure was intermittent polyethylene glycol (PEG) 4000 by nasogastric tube. Second-level measures were enema, neostigmine, and continuous PEG. Primary endpoints were the prevalence of constipation for the observational phase and the number of patients that failed to achieve defecation with first-level measures for the treatment and prophylaxis phases. RESULTS: Paralysis of lower gastrointestinal tract in the observational phase was found in 57 of 63 patients (90.5%). Failure to achieve defecation with the first-level measure occurred in 16 of 64 patients (25%) in the treatment phase and in 6 of 70 patients (8.6%) in the prophylaxis phase (P=0.01). Eighteen measures of second level were applied in the treatment phase and 6 in the prophylaxis phase. CONCLUSIONS: Paralysis of the lower gastrointestinal tract in mechanically ventilated ICU patients is common. PEG given as prophylaxis on the first day after mechanical ventilation is associated with faster resolution of paralysis of gastrointestinal tract than PEG given as a treatment on day 4.

Effectiveness of Vortioxetine in Patients with Major Depressive Disorder Associated with Chronic Pain: An Observational Study in a Spanish Population.

INTRODUCTION: Chronic pain (CP) and depression/anxiety often coexist, worsening each other's symptoms. Treating this comorbidity is challenging. Tricyclic antidepressants and serotonin noradrenaline reuptake inhibitors are the first-line treatment options for this comorbidity, although sometimes they are not effective and/or well tolerated by patients, and there is little clinical evidence that selective serotonin reuptake inhibitors are useful for controlling CP. The antidepressant vortioxetine, with a multimodal mechanism that may help reduce pain, has proven clinical efficacy in patients with major depressive disorder (MDD). This study investigated vortioxetine's effectiveness for MDD and CP in clinical practice. METHODS: This was a 3-month, multicenter, prospective, open-label, non-interventional pharmacoepidemiologic study. Patients (n = 64) with MDD (9-item Patient Health Questionnaire [PHQ-9] score ≥ 15) and CP (visual analogue scale [VAS] score ≥ 4) were treated with vortioxetine for 3 months (initiated with 10 mg/day, with flexible dosing thereafter [5-20 mg/day]). VAS, Clinical Global Impression (CGI), and Patient Global Impression (PGI) scales were used at baseline and at 1 and 3 months. Brief Pain Inventory (BPI), PHQ-9 scale, and Satisfaction with Medicines Questionnaire (SATMED-Q) were used at baseline and at 3 months. Adverse Events (AEs) were recorded. Descriptive statistics, chi-square tests, and Student's t-tests were used for paired data. RESULTS: MDD patients showed a statistically significant improvement in VAS from baseline (mean [standard deviation (SD)]: 7.42 [0.69]) to 1 month (mean [SD]: 6.1 [0.81], P < 0.001) and 3 months (mean [SD]: 5.09 [1.26], P < 0.0001). Similarly, BPI and PHQ-9 scores showed significant improvement from baseline (mean [SD]: 6.20 [0.80] and 16.63 [1.47], respectively) to 3 months (mean [SD]: 4.73 [0.98] and 7.30 [2.60], P < 0.0001, respectively). Patients showed clinical improvement with CGI and PGI scales and reported being satisfied with the treatment in the SATMED-Q. A few mild EAs were registered. CONCLUSION: Vortioxetine can relieve depressive and pain symptoms, with a good safety profile, in patients with MDD and CP.

The effect of temperature and excitation energy on Raman scattering in bulkHfS2.

Raman scattering (RS) in bulk hafnium disulfide (HfS2) is investigated as a function of temperature (5 K - 350 K) with polarization resolution and excitation of several laser energies. An unexpected temperature dependence of the energies of the main Raman-active (A1gand Eg) modes with the temperature-induced blueshift in the low-temperature limit is observed. The low-temperature quenching of a modeω1(134 cm-1) and the emergence of a new mode at approx. 184 cm-1, labeledZ, is reported. The optical anisotropy of the RS inHfS2is also reported, which is highly susceptible to the excitation energy. The apparent quenching of the A1gmode atT = 5 K and of the Egmode atT= 300 K in the RS spectrum excited with 3.06 eV excitation is also observed. We discuss the results in the context of possible resonant character of light-phonon interactions. Analyzed is also a possible effect of the iodine molecules intercalated in the van der Waals gaps between neighboringHfS2layers, which inevitably result from the growth procedure.

High-Pressure Vibrational and Structural Properties of Ni3V2O8 and Co3V2O8 up to 20 GPa.

The vibrational and structural behaviors of Ni3V2O8 and Co3V2O8 orthovanadates have been studied up to around 20 GPa by means of X-ray diffraction, Raman spectra, and theoretical simulations. Both materials crystallize in an orthorhombic Kagomé staircase structure (space group: Cmca) at ambient conditions, and no phase transition was found in the whole pressure range. In order to identify the symmetry of the detected Raman-active modes under high pressure, single crystal samples of those materials were used in a polarized Raman and infrared setup. Moreover, high-pressure powder X-ray diffraction measurements were performed for Co3V2O8, and the results confirmed the structure stability also obtained by other diagnostic techniques. From this XRD analysis, the anisotropic compressibilities of all axes were calculated and the unit-cell volume vs pressure was fitted by a Birch-Murnaghan equation of state, obtaining a bulk modulus of 122 GPa.

Potential effects of corticosteroids on physiological dead-space fraction in acute respiratory distress syndrome.

BACKGROUND: Increased dead-space fraction is common in patients with persistent acute respiratory distress syndrome (ARDS). We evaluated the changes in the oxygenation and dead-space fraction in patients with persistent ARDS after corticosteroid therapy. METHODS: This was a non-randomized non-placebo, controlled observational study including 19 patients with persistent ARDS treated with corticosteroids. We measured P(aO(2))/F(IO(2)) and dead-space fraction at days 0, 4, and 7 after corticosteroids treatment (methylprednisolone) initiation. Patients were classified in intermediate group when corticosteroids were initiated between days 8-14 after ARDS onset, and in late group when initiated after 14 days. RESULTS: Mean time from the diagnosis of the ARDS to methylprednisolone treatment was 11 ± 2 days in the intermediate group (10 patients) and 21 ± 8 days in the late group (9 patients). When comparing days 0, 4, and 7 after methylprednisolone treatment, we found an increase in the P(aO(2))/F(IO(2)) (145 ± 64 mm Hg, 190 ± 68 mm Hg, and 226 ± 84 mm Hg, respectively, P < .001) and a decrease in the physiological dead-space fraction (0.66 ± 0.10, 0.58 ± 0.12, and 0.53 ± 0.11, respectively, P < .001). No differences were found between the intermediate and late groups. CONCLUSIONS: In patients with persistent ARDS, the increase in oxygenation was accompanied by a decrease in the dead-space fraction after a few days of corticosteroid treatment. To confirm potential benefit of corticosteroids on physiological parameters and mortality will require a powered randomized placebo controlled trial.

CO2 response and duration of weaning from mechanical ventilation.

BACKGROUND: The CO2 response test measures the hypercapnic drive response (which is defined as the ratio of the change in airway-occlusion pressure 0.1 s after the start of inspiratory flow [ΔP(0.1)] to the change in P(aCO2) [ΔP(aCO2)]), and the hypercapnic ventilatory response (which is defined as the ratio of the change in minute volume to ΔP(aCO2)). OBJECTIVE: In mechanically ventilated patients ready for a spontaneous breathing trial, to investigate the relationship between CO2 response and the duration of weaning. METHODS: We conducted the CO2 response test and measured maximum inspiratory pressure (P(Imax)) and maximum expiratory pressure (P(Emax)) in 102 non-consecutive ventilated patients. We categorized the patients as either prolonged weaning (weaning duration > 7 d) or non-prolonged weaning (≤ 7 d). RESULTS: Twenty-seven patients had prolonged weaning. Between the prolonged and non-prolonged weaning groups we found differences in hypercapnic drive response (0.22 ± 0.16 cm H2O/mm Hg vs 0.47 ± 0.22 cm H2O/mm Hg, respectively, P < .001) and hypercapnic ventilatory response (0.25 ± 0.23 L/min/mm Hg vs 0.53 ± 0.33 L/min/mm Hg, respectively, P < .001). The optimal cutoff points to differentiate between prolonged and non-prolonged weaning were 0.19 cm H2O/mm Hg for hypercapnic drive response, and 0.15 L/min/mm Hg for hypercapnic ventilatory response. Assessed with the Cox proportional hazards model, both hypercapnic drive response and hypercapnic ventilatory response were independent variables associated with the duration of weaning. The hazard ratio of weaning success was 16.7 times higher if hypercapnic drive response was > 0.19 cm H2O/mm Hg, and 6.3 times higher if hypercapnic ventilatory response was > 0.15 L/min/mm Hg. Other variables (P(0.1), P(Imax), and P(Emax)) were not associated with the duration of the weaning. CONCLUSIONS: Decreased CO2 response, as measured by hypercapnic drive response and hypercapnic ventilatory response, are associated with prolonged weaning.

Hypoxic hepatitis in critically ill patients: incidence, etiology and risk factors for mortality.

PURPOSE: Hypoxic hepatitis may be induced by hemodynamic instability or arterial hypoxemia in critically ill patients. We investigated the incidence, etiology, association with systemic ischemic injury and risk factors for mortality in this population. METHODS: Retrospective analysis of patients with hypoxic hepatitis admitted to a multidisciplinary intensive care unit (ICU) of a university hospital. Hypoxic hepatitis was defined as the existence of a compatible clinical setting (cardiocirculatory failure or arterial hypoxemia) and aminotransferase levels higher than 1000 IU/L. RESULTS: During the 8-year study period, 182 out of the 7674 patients admitted presented hypoxic hepatitis (2.4%). The most common cause was septic shock. The rate of in-hospital mortality in hypoxic hepatitis was 61.5% (112 patients), and was higher in patients with septic shock (83.3%) and cardiac arrest (77.7%). Ischemic pancreatitis (25.6%), rhabdomyolysis (41.2%) and renal failure (67.2%) were common in these patients. Risk factors of mortality were prolonged INR (p = 0.005), need for renal replacement therapy (p = 0.001) and septic shock (p = 0.005). CONCLUSIONS: Hypoxic hepatitis was not a rare condition, and was frequently accompanied by multiorgan injury, with high mortality. Risk factors for increased mortality were prolonged INR, need for renal replacement therapy, and septic shock.

Unveiling the role of the lone electron pair in sesquioxides at high pressure: compressibility of ß-Sb2O3.

The structural, vibrational and electronic properties of the compressed ß-Sb2O3 polymorph, a.k.a. mineral valentinite, have been investigated in a joint experimental and theoretical study up to 23 GPa. The compressibility of the lattice parameters, unit-cell volume and polyhedral unit volume as well as the behaviour of its Raman- and IR-active modes under compression have been interpreted on the basis of ab initio theoretical simulations. Valentinite shows an unusual compressibility up to 15 GPa with four different pressure ranges, whose critical pressures are 2, 4, and 10 GPa. The pressure dependence of the main structural units, the lack of soft phonons, and the electronic density charge topology address the changes at those critical pressures to isostructural phase transitions of degree higher than 2. In particular, the transitions at 2 and 4 GPa can be ascribed to the changes in the interaction between the stereochemically-active lone electron pairs of Sb atoms under compression. The changes observed above 10 GPa, characterized by a general softening of several Raman- and IR-active modes, point to a structural instability prior to the 1st-order transition occurring above 15 GPa. Above this pressure, a tentative new high-pressure phase (s.g. Pcc2) has been assigned by single-crystal and powder X-ray diffraction measurements.

Lack of effect of glutamine administration to boost the innate immune system response in trauma patients in the intensive care unit.

INTRODUCTION: The use of glutamine as a dietary supplement is associated with a reduced risk of infection. We hypothesized that the underlying mechanism could be an increase in the expression and/or functionality of Toll-like receptors (TLR), key receptors sensing infections. The objective of this study was to evaluate whether glutamine supplementation alters the expression and functionality of TLR2 and TLR4 in circulating monocytes of trauma patients admitted to the intensive care unit (ICU). METHODS: We designed a prospective, randomized and single-blind study. Twenty-three patients received parenteral nutrition (TPN) with a daily glutamine supplement of 0.35 g/kg. The control group (20 patients) received an isocaloric-isonitrogenated TPN. Blood samples were extracted before treatment, at 6 and 14 days. Expression of TLR2 and TLR4 was determined by flow cytometry. Monocytes were stimulated with TLR specific agonists and cytokines were measured in cell culture supernatants. Phagocytic ability of monocytes was also determined. RESULTS: Basal characteristics were similar in both groups. Monocytes from patients treated with glutamine expressed the same TLR2 levels as controls before treatment (4.9 ± 3.5 rmfi vs. 4.3 ± 1.9 rmfi, respectively; P = 0.9), at Day 6 (3.8 ± 2.3 rmfi vs. 4.0 ± 1.7 rmfi, respectively; P = 0.7) and at Day 14 (4.1 ± 2.1 rfim vs. 4.6 ± 1.9 rmfi, respectively; P = 0.08). TLR4 levels were not significantly different between the groups before treatment: (1.1 ± 1 rmfi vs 0.9 ± 0.1 rmfi respectively; P = 0.9), at Day 6 (1.1 ± 1 rmfi vs. 0.7 ± 0.4 rmfi respectively; P = 0.1) and at Day 14 (1.4 ± 1.9 rmfi vs. 1.0 ± 0.6 rmfi respectively; P = 0.8). No differences in cell responses to TLR agonists were found between groups. TLR functionality studied by phagocytosis did not vary between groups. CONCLUSIONS: In trauma patients in the intensive care unit, TPN supplemented with glutamine does not improve the expression or the functionality of TLRs in peripheral blood monocytes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01250080.

Hypercapnic respiratory failure in obesity-hypoventilation syndrome: CO2 response and acetazolamide treatment effects.

OBJECTIVE: In obesity-hypoventilation-syndrome patients mechanically ventilated for hypercapnic respiratory failure we investigated the relationship between CO2 response, body mass index, and plasma bicarbonate concentration, and the effect of acetazolamide on bicarbonate concentration and CO2 response. METHODS: CO2 response tests and arterial blood gas analysis were performed in 25 patients ready for a spontaneous breathing test, and repeated in a subgroup of 8 patients after acetazolamide treatment. CO2 response test was measured as (1) hypercapnic drive response (the ratio of the change in airway occlusion pressure 0.1 s after the start of inspiratory flow to the change in P(aCO2)), and (2) hypercapnic ventilatory response (the ratio of the change in minute volume to the change in P(aCO2)). RESULTS: We did not find a significant relationship between CO2 response and body mass index. Patients with higher bicarbonate concentration had a more blunted CO2 response. Grouping the patients according to the first, second, and third tertiles of the bicarbonate concentration, the hypercapnic drive response was 0.32 ± 0.17 cm H2O/mm Hg, 0.22 ± 0.15 cm H2O/mm Hg, and 0.10 ± 0.06 cm H2O/mm Hg, respectively (P = .01), and hypercapnic ventilatory response was 0.46 ± 0.23 L/min/mm Hg, 0.48 ± 0.36 L/min/mm Hg, and 0.22 ± 0.16 L/min/mm Hg, respectively (P = .04). After acetazolamide treatment, bicarbonate concentration was reduced by 8.4 ± 3.0 mmol/L (P = .01), and CO2 response was shifted to the left, with an increase in hypercapnic drive response, by 0.14 ± 0.16 cm H2O/mm Hg (P = .02), and hypercapnic ventilatory response, by 0.11 ± 0.22 L/min/mm Hg (P = .33). CONCLUSIONS: Patients with obesity-hypoventilation syndrome and higher bicarbonate concentrations had a more blunted CO2 response. Body mass index was not related to CO2 response. Acetazolamide decreased bicarbonate concentration and increased CO2 response.

Prognostic value of the pulmonary dead-space fraction during the early and intermediate phases of acute respiratory distress syndrome.

BACKGROUND: Little is known about the alveolar dead-space fraction after the first week of acute respiratory distress syndrome (ARDS). We measured the dead-space fraction in the early phase (first week) and the intermediate phase (second week) of ARDS, and evaluated the association of dead-space fraction with mortality. METHODS: We prospectively measured dead-space fraction and other variables in 80 intubated patients during the early phase of ARDS and in 49 patients during the intermediate phase. We used multiple logistic regression analysis to evaluate data. The primary outcome was in-hospital mortality. RESULTS: In the early and intermediate phases the dead-space fraction was higher in patients who died than among those who survived (dead-space fraction 0.64 +/- 0.09 vs 0.53 +/- 0.11, P < .001, and 0.62 +/- 0.09 vs 0.50 +/- 0.10, P < .001, respectively). In both the early and intermediate phases the dead-space fraction was independently associated with a greater risk of death. For every dead-space-fraction increase of 0.05 the odds of death increased by 59% in the early phase (odds ratio 1.59, 95% confidence interval 1.18-2.16, P = .003) and by 186% in the intermediate phase (odds ratio 2.87, 95% confidence interval 1.36-6.04, P = .005). Age and Sequential Organ Failure Assessment score were also independently associated with a greater risk of death in both phases. CONCLUSIONS: Increased alveolar dead-space fraction in the early and intermediate phases of ARDS is associated with a greater risk of death.

Incidence and outcome of ischemic hepatitis complicating septic shock.

AIM: The specific incidence of ischemic hepatitis in septic shock patients remains unknown. The aim of this study was to evaluate the incidence of ischemic hepatitis in septic shock and its relationship with mortality. METHODS: We retrospectively studied 181 patients with septic shock admitted to the intensive care unit (ICU). We defined ischemic hepatitis as having a value of serum aminotransferases equal to or higher than 1000 IU/L. We recorded the age, sex, comorbidity, site of infection, the Sequential Organ Failure Assessment (SOFA) score on admission to the ICU, maximum SOFA score and inadequate antibiotic therapy. RESULTS: Twenty-five (13.8%) patients developed ischemic hepatitis. In-hospital mortality was 57% (103 patients). In the ischemic hepatitis group, mortality increased up to 84.0% (21 patients) compared with 52.6% (82 patients) in patients without ischemic hepatitis (control group) (odds ratio [OR]: 4.7; 95% confidence interval [CI]: 1.6-14.4; P = 0.003). The development of ischemic hepatitis, age, maximum SOFA score and inadequate antibiotic therapy were independently associated with an increased risk of death. The odds of death increased by 247% in ischemic hepatitis (OR: 3.47; 95% CI: 1.02-11.8; P = 0.047). CONCLUSION: Ischemic hepatitis is a common complication in septic shock patients, associated with a high mortality.

Pentobarbital versus thiopental in the treatment of refractory intracranial hypertension in patients with traumatic brain injury: a randomized controlled trial.

INTRODUCTION: Experimental research has demonstrated that the level of neuroprotection conferred by the various barbiturates is not equal. Until now no controlled studies have been conducted to compare their effectiveness, even though the Brain Trauma Foundation Guidelines recommend that such studies be undertaken. The objectives of the present study were to assess the effectiveness of pentobarbital and thiopental in terms of controlling refractory intracranial hypertension in patients with severe traumatic brain injury, and to evaluate the adverse effects of treatment. METHODS: This was a prospective, randomized, cohort study comparing two treatments: pentobarbital and thiopental. Patients who had suffered a severe traumatic brain injury (Glasgow Coma Scale score after resuscitation < or = 8 points or neurological deterioration during the first week after trauma) and with refractory intracranial hypertension (intracranial pressure > 20 mmHg) first-tier measures, in accordance with the Brain Trauma Foundation Guidelines. RESULTS: A total of 44 patients (22 in each group) were included over a 5-year period. There were no statistically significant differences in ' baseline characteristics, except for admission computed cranial tomography characteristics, using the Traumatic Coma Data Bank classification. Uncontrollable intracranial pressure occurred in 11 patients (50%) in the thiopental treatment group and in 18 patients (82%) in the pentobarbital group (P = 0.03). Under logistic regression analysis--undertaken in an effort to adjust for the cranial tomography characteristics, which were unfavourable for pentobarbital--thiopental was more effective than pentobarbital in terms of controlling intracranial pressure (odds ratio = 5.1, 95% confidence interval 1.2 to 21.9; P = 0.027). There were no significant differences between the two groups with respect to the incidence of arterial hypotension or infection. CONCLUSIONS: Thiopental appeared to be more effective than pentobarbital in controlling intracranial hypertension refractory to first-tier measures. These findings should be interpreted with caution because of the imbalance in cranial tomography characteristics and the different dosages employed in the two arms of the study. The incidence of adverse effects was similar in both groups. TRIAL REGISTRATION: (Trial registration: US Clinical Trials registry NCT00622570.).

Glutamine as a modulator of the immune system of critical care patients: effect on Toll-like receptor expression. A preliminary study.

OBJECTIVE: We evaluated the expression of Toll-like receptors 2 and 4 (TLR-2 and TLR-4) in circulating monocytes from peripheral blood of critical care patients treated with and without glutamine. Because no research has been published to date on the effect of glutamine on TLR receptors in critical patients, it was determined in an initial sample of 30 patients. METHODS: This was a prospective, randomized, single-blind study with 15 patients assigned to receive parenteral nutrition with a daily glutamine supplement of 0.35 g/kg. The control group received isocaloric-isonitrogenous parenteral nutrition. Blood samples were extracted before beginning the treatment and at 5 and 14 d. Expressions of CD14, TLR-2, and TLR-4 were determined by flow cytometry. Levels of TLRs were expressed as mean fluorescence intensity (mfi). RESULTS: Basal characteristics were similar in both groups. The expressions of TLR-2 in the treatment group with glutamine were 4.67 +/- 3.82 mfi before treatment, 3.91 +/- 2.04 mfi at 5 d, and 4.28 +/- 2.47 mfi at 14 d. The expressions of TLR-2 in the control group were 5.49 +/- 3.20 mfi before treatment, 4.48 +/- 2.15 mfi at 5 d, and 4.36 +/- 2.36 mfi at 14 d. The expressions of TLR-4 in the treatment group were 1.65 +/- 1.89 mfi before treatment, 1.23 +/- 1.10 mfi at 5 d, and 1.77 +/- 1.97 at 14 d. The expressions of TLR-4 in the control group were 1.51 +/- 1.76 mfi before treatment, 1.36 +/- 0.99 mfi at 5 d, and 1.26 +/- 0.59 mfi at 14 d. Infections were detected in 11 patients who received glutamine and 13 control patients (P = 0.51). CONCLUSION: In critical care patients, parenteral nutrition supplemented with glutamine does not increase the expression of TLR-2 or TLR-4 in peripheral blood monocytes.

Hypercapnia test as a predictor of success in spontaneous breathing trials and extubation.

BACKGROUND: The ventilatory capacity of the respiratory neuromuscular system can be studied with the hypercapnia test. OBJECTIVE: To determine whether decreased response to the hypercapnia test is associated with failure to pass a spontaneous breathing trial (SBT) or extubation failure. METHODS: We studied 103 intubated patients ready for SBT. We used a hypercapnia test in which we approximately doubled the dead space and thus caused re-inhalation of expired air. We calculated 3 ratios: the ratio of P(0.1) (airway occlusion pressure 0.1 s after the onset of inspiratory effort) during hypercapnia test to baseline P(0.1); the ratio of the change in minute volume [DeltaV(E)] to the change in P(aCO(2)) (we call this ratio the hypercapnic ventilatory response); and the ratio of the change in P(0.1) [DeltaP(0.1)] to the change P(aCO(2)) (we call this ratio the hypercapnic-respiratory-drive response). RESULTS: Thirty-six patients failed the SBT, and 11 patients failed extubation. The mean values for the SBT/extubation-success group, the extubation-failure group, and the SBT-failure group, respectively, were: ratio of hypercapnia-test P(0.1) to baseline P(0.1): 4.3 +/- 2.7, 3.7 +/- 1.3, and 3.0 +/- 1.8 (P = .03); hypercapnic ventilatory response: 0.60 +/- 0.35 L/min/mm Hg, 0.50 +/- 0.26 L/min/mm Hg, and 0.31 +/- 0.21 L/min/mm Hg (P < .001); hypercapnic respiratory-drive response: 0.48 +/- 0.24 cm H(2)O/mm Hg, 0.42 +/- 0.19 cm H(2)O/mm Hg, and 0.27 +/- 0.15 cm H(2)O/mm Hg (P < .001). For predicting SBT/extubation success, the sensitivities and specificities, respectively, were: ratio of hypercapnia-test P(0.1) to baseline P(0.1) 0.80 and 0.47; hypercapnic ventilatory response 0.86 and 0.53; hypercapnic respiratory-drive response 0.82 and 0.55. CONCLUSIONS: The SBT/extubation-failure patients had less response to the hypercapnia test than did the SBT/extubation-success patients, and the hypercapnia test was not useful in predicting SBT or extubation success.

Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain.

CONTEXT: Concern exists that current guidelines for care of patients with severe sepsis and septic shock are followed variably, possibly due to a lack of adequate education. OBJECTIVE: To determine whether a national educational program based on the Surviving Sepsis Campaign guidelines affected processes of care and hospital mortality for severe sepsis. DESIGN, SETTING, AND PATIENTS: Before and after design in 59 medical-surgical intensive care units (ICUs) located throughout Spain. All ICU patients were screened daily and enrolled if they fulfilled severe sepsis or septic shock criteria. A total of 854 patients were enrolled in the preintervention period (November-December 2005), 1465 patients during the postintervention period (March-June 2006), and 247 patients during the long-term follow-up period 1 year later (November-December 2006) in a subset of 23 ICUs. INTERVENTION: The educational program consisted of training physicians and nursing staff from the emergency department, wards, and ICU in the definition, recognition, and treatment of severe sepsis and septic shock as outlined in the guidelines. Treatment was organized in 2 bundles: a resuscitation bundle (6 tasks to begin immediately and be accomplished within 6 hours) and a management bundle (4 tasks to be completed within 24 hours). MAIN OUTCOME MEASURES: Hospital mortality, differences in adherence to the bundles' process-of-care variables, ICU mortality, 28-day mortality, hospital length of stay, and ICU length of stay. RESULTS: Patients included before and after the intervention were similar in terms of age, sex, and Acute Physiology and Chronic Health Evaluation II score. At baseline, only 3 process-of-care measurements (blood cultures before antibiotics, early administration of broad-spectrum antibiotics, and mechanical ventilation with adequate inspiratory plateau pressure) we had compliance rates higher than 50%. Patients in the postintervention cohort had a lower risk of hospital mortality (44.0% vs 39.7%; P = .04). The compliance with process-of-care variables also improved after the intervention in the sepsis resuscitation bundle (5.3% [95% confidence interval [CI], 4%-7%] vs 10.0% [95% CI, 8%-12%]; P < .001) and in the sepsis management bundle (10.9% [95% CI, 9%-13%] vs 15.7% [95% CI, 14%-18%]; P = .001). Hospital length of stay and ICU length of stay did not change after the intervention. During long-term follow-up, compliance with the sepsis resuscitation bundle returned to baseline but compliance with the sepsis management bundle and mortality remained stable with respect to the postintervention period. CONCLUSIONS: A national educational effort to promote bundles of care for severe sepsis and septic shock was associated with improved guideline compliance and lower hospital mortality. However, compliance rates were still low, and the improvement in the resuscitation bundle lapsed by 1 year.