Population Pharmacokinetics of Anidulafungin in Critically Ill Patients.

A two-compartment pharmacokinetic (PK) population model of anidulafungin was fitted to PK data from 23 critically ill patients (age, 65 years [range, 28 to 81 years]; total body weight [TBW], 75 kg [range, 54 to 168 kg]). TBW was associated with clearance and incorporated into a final population PK model. Simulations suggested that patients with higher TBWs had less-extensive MIC coverage. Dosage escalation may be warranted in patients with high TBWs to ensure optimal drug exposures for treatment of Candida albicans and Candida glabrata infections.

Clinical significance and outcome of Aeromonas spp. infections among 204 adult patients.

The objectives of this investigation were to analyze the clinical patterns, risk groups, prognostic factors, and mortality of infections caused by Aeromonas spp. This was a retrospective study of adult patients with Aeromonas spp. isolates attended at the Hospital del Mar in Barcelona, Spain, between January 2006 and December 2012. Epidemiological data, antimicrobial susceptibility, clinical patterns, underlying illnesses, type of infection, admission to the intensive care unit (ICU), number of episodes, coinfection, antimicrobial therapy, and evolution were analyzed. A total of 221 clinical samples from 204 patients were positive for Aeromonas spp. The mean age of the patients was 67.6 years. The main clinical form of presentation was gastrointestinal (78.4%). Malignancy was the main risk group in 69 (33.8%) patients, and 48 (23.5%) were previously healthy. Twenty-one patients (10.3%) were admitted to the ICU. Infections were acquired in the hospital in 52.5% of the patients, and 28.9% were polymicrobial. The overall mortality (after 1 year of follow-up from the first positive culture) was 26.5%. Univariate analysis identified an association between increased mortality and the following variables: age ≥80 years, hospitalization, admission to the ICU, malignancy, extraintestinal infection, and appropriate antimicrobial therapy. In the multivariate analysis, age ≥80 years [odds ratio (OR), 4.37 [95% confidence interval (CI), 1.68-11.35; p = 0.002]], admission to the ICU (OR, 6.59 [95% CI, 2.17-19.99; p = 0.001]), and malignancy (OR, 3.62 [95% CI, 1.32-9.90; p = 0.012]) were significantly associated with mortality. Aeromonas infections are mainly gastrointestinal. The 1-year follow-up mortality rate was high. Old age (age ≥80 years), admission to the ICU, and malignancy were identified as independent risk factors for mortality.

The role of high flow oxygen therapy in acute respiratory failure.

Acute respiratory failure represents one of the most common causes of intensive care unit admission and oxygen therapy remains the first-line therapy in the management of these patients. In recent years, high-flow oxygen via nasal cannula has been described as a useful alternative to conventional oxygen therapy in patients with acute respiratory failure. High-flow oxygen via nasal cannula rapidly alleviates symptoms of acute respiratory failure and improves oxygenation by several mechanisms, including dead space washout, reduction in oxygen dilution and inspiratory nasopharyngeal resistance, a moderate positive airway pressure effect that may generate alveolar recruitment and an overall greater tolerance and comfort with the interface and the heated and humidified inspired gases. However, the experience in adults is still limited and there are no clinical guidelines to establish recommendations for their use. This article aims to review the existing evidence on the use of high-flow oxygen via nasal cannula in adults with acute respiratory failure and its possible applications, advantages and limitations.

Solid organ transplant training objectives for residents.

With the aim of analyzing the current state of the educational objectives in the training of medical residents in solid organ transplantation (SOT), we conducted a review of the status of the official programs of the specialities involved in SOT, focusing particularly on lung transplantation. A survey of medical residents was also conducted to allow reflexion about the topic. We obtained 44 surveys from 4 University Hospitals with active programs in SOT, mainly from intensive care medicine and anesthesiology residents. We detected an important number of courses oriented to organ donation but very limited in terms of basic training in the management of the immediate postoperative period, principles of immunosuppression and updates on immunosuppressive therapy and complications (particularly rejection and infection). We also identified that these educational aspects should be directed not only to medical residents from specialities with a close retation to SOT, but also to all who may at some time have a relation to such patients. The use of information and communication techniques (ICTs), on-line courses and also simulations should be instruments to take into account in the biomedical training of medical residents. We conclude that we need a specific training program in complications of SOT, as well as fundamental principles in immunology and immunosuppressor pharmacology.

[Electrical impedance tomography in acute lung injury]. / Tomografía de impedancia eléctrica en la lesión pulmonar aguda.

Electrical impedance tomography has been described as a new method of monitoring critically ill patients on mechanical ventilation. It has recently gained special interest because of its applicability for monitoring ventilation and pulmonary perfusion. Its bedside and continuous implementation, and the fact that it is a non-ionizing and non-invasive technique, makes it an extremely attractive measurement tool. Likewise, given its ability to assess the regional characteristics of lung structure, it could be considered an ideal monitoring tool in the heterogeneous lung with acute lung injury. This review explains the physical concept of bioimpedance and its clinical application, and summarizes the scientific evidence published to date with regard to the implementation of electrical impedance tomography as a method for monitoring ventilation and perfusion, mainly in the patient with acute lung injury, and other possible applications of the technique in the critically ill patient. The review also summarizes the limitations of the technique and its potential areas of future development.

Active humidification in mechanical ventilation is not associated to an increase in respiratory infectious complications in a quasi-experimental pre-post intervention study.

OBJECTIVE: There is controversy regarding the influence of humidification systems upon the incidence of respiratory infections associated to invasive mechanical ventilation (IMV). An evaluation was made of the differences in the incidence of pneumonia and tracheobronchitis associated to mechanical ventilation (VAP and VAT, respectively) with passive and active humidification. DESIGN: A retrospective pre-post quasi-experimental study was carried out. SETTING: A polyvalent ICU with 14 beds. PATIENTS: All patients connected to IMV for >48h during 2014 and 2016 were included. INTERVENTIONS: During 2014, passive humidification with an hygroscopic heat and moisture exchanger (HME) was used, while during 2016 active humidification with a heated humidifier (HH) and an inspiratory heated wire was used. Identical measures for the prevention of VAP were established (Zero Pneumonia Project). MAIN OUTCOME MEASURES: The incidence of VAP and VAT was estimated for 1000 days of IMV in both groups, and statistically significant differences were assessed using Poisson regression analysis. RESULTS: A total of 287 patients were included (116 with HME and 171 with HH). The incidence density of VAP per 1000 days of IMV was 5.68 in the HME group and 5.80 in the HH group (p=ns). The incidence density of VAT was 3.41 and 3.26 cases per 1000 days of VMI with HME and HH respectively (p=ns). The duration of IMV was identified as a risk factor for VAP. CONCLUSIONS: In our population, active humidification in patients ventilated for >48h was not associated to an increase in respiratory infectious complications.

Structural differences in the diaphragm of patients following controlled vs assisted and spontaneous mechanical ventilation.

PURPOSE: Ventilator-induced diaphragm dysfunction or damage (VIDD) is highly prevalent in patients under mechanical ventilation (MV), but its analysis is limited by the difficulty of obtaining histological samples. In this study we compared diaphragm histological characteristics in Maastricht III (MSIII) and brain-dead (BD) organ donors and in control subjects undergoing thoracic surgery (CTL) after a period of either controlled or spontaneous MV (CMV or SMV). METHODS: In this prospective study, biopsies were obtained from diaphragm and quadriceps. Demographic variables, comorbidities, severity on admission, treatment, and ventilatory variables were evaluated. Immunohistochemical analysis (fiber size and type percentages) and quantification of abnormal fibers (a surrogate of muscle damage) were performed. RESULTS: Muscle samples were obtained from 35 patients. MSIII (n = 16) had more hours on MV (either CMV or SMV) than BD (n = 14) and also spent more hours and a greater percentage of time with diaphragm stimuli (time in assisted and spontaneous modalities). Cross-sectional area (CSA) was significantly reduced in the diaphragm and quadriceps in both groups in comparison with CTL (n = 5). Quadriceps CSA was significantly decreased in MSIII compared to BD but there were no differences in the diaphragm CSA between the two groups. Those MSIII who spent 100 h or more without diaphragm stimuli presented reduced diaphragm CSA without changes in their quadriceps CSA. The proportion of internal nuclei in MSIII diaphragms tended to be higher than in BD diaphragms, and their proportion of lipofuscin deposits tended to be lower, though there were no differences in the quadriceps fiber evaluation. CONCLUSIONS: This study provides the first evidence in humans regarding the effects of different modes of MV (controlled, assisted, and spontaneous) on diaphragm myofiber damage, and shows that diaphragm inactivity during mechanical ventilation is associated with the development of VIDD.

Severe vitamin D deficiency upon admission in critically ill patients is related to acute kidney injury and a poor prognosis. / La hipovitaminosis D grave al ingreso en el paciente crítico se asocia a fracaso renal agudo y mal pronóstico.

OBJECTIVES: To evaluate the prevalence of vitamin D deficiency in critically ill patients upon admission to an Intensive Care Unit (ICU) and its prognostic implications. DESIGN: A single-center, prospective observational study was carried out from January to November 2015. Patients were followed-up on until death or hospital discharge. SETTING: The department of Critical Care Medicine of a university hospital. PATIENTS: All adults admitted to the ICU during the study period, without known factors capable of altering serum 25(OH)D concentration. INTERVENTIONS: Determination of serum 25(OH)D levels within the first 24h following admission to the ICU. MAIN VARIABLES OF INTEREST: Prevalence and mortality at 28 days. RESULTS: The study included 135 patients, of which 74% presented deficient serum 25(OH)D levels upon admission to the ICU. Non-survivors showed significantly lower levels than survivors (8.14ng/ml [6.17-11.53] vs. 12ng/ml [7.1-20.30]; P=.04], and the serum 25(OH)D levels were independently associated to mortality (OR 2.86; 95% CI 1.05-7.86; P=.04]. The area under the ROC curve was 0.61 (95% CI 0.51-0.75), and the best cut-off point for predicting mortality was 10.9ng/ml. Patients with serum 25(OH)D<10.9ng/ml also showed higher acute kidney injury rates (13 vs. 29%; P=.02). CONCLUSION: Vitamin D deficiency is highly prevalent upon admission to the ICU. Severe Vitamin D deficiency (25[OH]D<10.9ng/ml) upon admission to the ICU is associated to acute kidney injury and mortality.

Patients with influenza A (H1N1)pdm09 admitted to the ICU. Impact of the recommendations of the SEMICYUC. / Pacientes con gripe por el virus influenza A (H1N1)pdm09 ingresados en la UCI. Impacto de las recomendaciones de la SEMICYUC.

OBJECTIVES: To evaluate the impact of the recommendations of the SEMICYUC (2012) on severe influenza A. DESIGN: A prospective multicenter observational study was carried out. SETTING: ICU. PATIENTS: Patients infected with severe influenza A (H1N1) from the GETGAG/SEMICYUC registry. INTERVENTIONS: Analysis of 2 groups according to the epidemic period of the diagnosis (2009-2011; 2013-2015). VARIABLES: Demographic, temporal, comorbidities, severity, treatments, mortality, late diagnosis and place of acquisition. RESULTS: A total of 2,205 patients were included, 1,337 (60.6%) in the first period and 868 (39.4%) in the second one. Age and severity on admission were significantly greater in the second period, as well as co-infection. With regard to the impact of the recommendations, in the second period the diagnosis was established earlier (70.8 vs. 61.1%, P<.001), without changes in the start of treatment. Patients received less corticosteroid treatment (39.7 vs. 44.9%, P<.05), more NIMV was used (47.4 vs. 33.2%, P<.001) and more vaccination was made (11.1 vs. 1.7%, P<.001), without changes in mortality (24.2 vs. 20.7%). A decrease in nosocomial infection was also noted (9.8 vs. 16%, P<.001). Patients needed less MV with more days of ventilation, more vasopressor drug use and more ventral decubitus. CONCLUSIONS: The management of patients with severe influenza A (H1N1) has changed over the years, though without changes in mortality. The recommendations of the SEMICYUC (2012) have allowed earlier diagnosis and improved corticosteroid use. Pending challenges are the delay in treatment, the vaccination rate and the use of NIMV.

Effects of erythropoietin on muscle O2 transport during exercise in patients with chronic renal failure.

Erythropoietin (rHuEPO) has proven to be effective in the treatment of anemia of chronic renal failure (CRF). Despite improving the quality of life, peak oxygen uptake after rHuEPO therapy is not improved as much as the increase in hemoglobin concentration ([Hb)] would predict. We hypothesized that this discrepancy is due to failure of O2 transport rates to rise in a manner proportional to [Hb]. To test this, eight patients with CRF undergoing regular hemodialysis were studied pre- and post-rHuEPO ([Hb] = 7.5 +/- 1.0 vs. 12.5 +/- 1.0 g x dl-1) using a standard incremental cycle exercise protocol. A group of 12 healthy sedentary subjects of similar age and anthropometric characteristics served as controls. Arterial and femoral venous blood gas data were obtained and coupled with simultaneous measurements of femoral venous blood flow (Qleg) by thermodilution to obtain O2 delivery and oxygen uptake (VO2). Despite a 68% increase in [Hb], peak VO2 increased by only 33%. This could be explained largely by reduced peak leg blood flow, limiting the gain in O2 delivery to 37%. At peak VO2, after rHuEPO, O2 supply limitation of maximal VO2 was found to occur, permitting the calculation of a value for muscle O2 conductance from capillary to mitochondria (DO2). While DO2 was slightly improved after rHuEPO, it was only 67% of that of sedentary control subjects. This kept maximal oxygen extraction at only 70%. Two important conclusions can be reached from this study. First, the increase in [Hb] produced by rHuEPO is accompanied by a significant reduction in peak blood flow to exercising muscle, which limits the gain in oxygen transport. Second, even after restoration of [Hb], O2 conductance from the muscle capillary to the mitochondria remains considerably below normal.

Cellular bioenergetics after erythropoietin therapy in chronic renal failure.

After erythropoietin (rHuEPO) therapy, patients with chronic renal failure (CRF) do not improve peak O2 uptake (VO2 peak) as much as expected from the rise in hemoglobin concentration ([Hb]). In a companion study, we explain this phenomenon by the concurrent effects of fall in muscle blood flow after rHuEPO and abnormal capillary O2 conductance observed in CRF patients. The latter is likely associated with a poor muscle microcirculatory network and capillary-myofiber dissociation due to uremic myopathy. Herein, cellular bioenergetics and its relationships with muscle O2 transport, before and after rHuEPO therapy, were examined in eight CRF patients (27 +/- 7.3 [SD] yr) studied pre- and post-rHuEPO ([Hb] = 7.8 +/- 0.7 vs. 11.7 +/- 0.7 g x dl-1) during an incremental cycling exercise protocol. Eight healthy sedentary subjects (26 +/- 3.1 yr) served as controls. We hypothesize that uremic myopathy provokes a cytosolic dysfunction but mitochondrial oxidative capacity is not abnormal. 31P-nuclear magnetic resonance spectra (31P-MRS) from the vastus medialis were obtained throughout the exercise protocol consisting of periods of 2 min exercise (at 1.67 Hz) at increasing work-loads interspersed by resting periods of 2.5 min. On a different day, after an identical exercise protocol, arterial and femoral venous blood gas data were obtained together with simultaneous measurements of femoral venous blood flow (Qleg) to calculate O2 delivery (QO2leg) and O2 uptake (VO2leg). Baseline resting [phosphocreatine] to [inorganic phosphate] ratio ([PCr]/[Pi]) did not change after rHuEPO (8.9 +/- 1.2 vs. 8.8 +/- 1.2, respectively), but it was significantly lower than in controls (10.9 +/- 1.5) (P = 0.01 each). At a given submaximal or peak VO2leg, no effects of rHuEPO were seen on cellular bioenergetics ([PCr]/[Pi] ratio, %[PCr] consumption halftime of [PCr] recovery after exercise), nor in intracellular pH (pHi). The post-rHuEPO bioenergetic status and pHi, at a given VO2leg, were below those observed in the control group. However, at a given pHi, no differences in 31P-MRS data were detected between post-rHuEPO and controls. After rHuEPO, at peak VO2, Qleg fell 20% (P < 0.04), limiting the change in QO2leg to 17%, a value that did not reach statistical significance. The corresponding O2 extraction ratio decreased from 73 +/- 4% to 68 +/- 8.2% (P < 0.03). These changes indicate that maximal O2 flow from microcirculation to mitochondria did not increase despite the 50% increase in [Hb] and explain how peak VO2leg and cellular bioenergetics (31P-MRS) did not change after rHuEPO. Differences in pHi, possibly due to lactate differences, between post-rHeEPO and controls appear to be a key factor in the abnormal muscle cell bioenergetics during exercise observed in CRF patients.

Characteristics of patients with hospital-acquired influenza A (H1N1)pdm09 virus admitted to the intensive care unit.

BACKGROUND: Influenza A (H1N1)pdm09 virus infection acquired in the hospital and in critically ill patients admitted to the intensive care unit (ICU) has been poorly characterized. AIM: To assess the clinical impact of hospital-acquired infection with influenza A (H1N1)pdm09 virus in critically ill patients. METHODS: Analysis of a prospective database of the Spanish registry (2009-2015) of patients with severe influenza A admitted to the ICU. Infection was defined as hospital-acquired when diagnosis and starting of treatment occurred from the seventh day of hospital stay with no suspicion on hospital admission, and community-acquired when diagnosis was established within the first 48 h of admission. FINDINGS: Of 2421 patients with influenza A (H1N1)pdm09 infection, 224 (9.3%) were classified as hospital-acquired and 1103 (45.6%) as community-acquired (remaining cases unclassified). Intra-ICU mortality was higher in the hospital-acquired group (32.9% vs 18.8%, P < 0.001). Independent factors associated with mortality were hospital-acquired influenza A (H1N1)pdm09 infection (odds ratio: 1.63; 95% confidence interval: 1.37-1.99), APACHE II score on ICU admission (1.09; 1.06-1.11), underlying haematological disease (3.19; 1.78-5.73), and need of extrarenal depuration techniques (4.20; 2.61-6.77) and mechanical ventilation (4.34; 2.62-7.21). CONCLUSION: Influenza A (H1N1)pdm09 infection acquired in the hospital is an independent factor for death in critically ill patients admitted to the ICU.

The Role of Omega-3 Polyunsaturated Fatty Acids in the Treatment of Patients with Acute Respiratory Distress Syndrome: A Clinical Review.

Acute respiratory distress syndrome (ARDS) is defined as the acute onset of noncardiogenic edema and subsequent gas-exchange impairment due to a severe inflammatory process. Recent report on the prognostic value of eicosanoids in patients with ARDS suggests that modulating the inflammatory response through the use of polyunsaturated fatty acids may be a useful strategy for ARDS treatment. The use of enteral diets enriched with eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) has reported promising results, showing an improvement in respiratory variables and haemodynamics. However, the interpretation of the studies is limited by their heterogeneity and methodology and the effect of ω-3 fatty acid-enriched lipid emulsion or enteral diets on patients with ARDS remains unclear. Therefore, the routine use of ω-3 fatty acid-enriched nutrition cannot be recommended and further large, homogeneous, and high-quality clinical trials need to be conducted to clarify the effectiveness of ω-3 polyunsaturated fatty acids.

Neurological disturbances and hyperdynamic shock in a patient with esophagocoloplasty.

A 39-year-old man, with no history of alcohol intake, who had had an esophago-ileo-colo-gastroplasty with ileotransversostomy, developed diplopia, seizures, metabolic acidosis, and cardiac failure and finally refractory hyperdynamic shock. He died 20 h after admission to our intensive care unit from cardiocirculatory collapse. Postmortem results revealed low erythrocyte transketolase activity, which was increased by 22% by in vitro addition of thiamine diphosphate (TDP effect). Cerebral pathology showed the alterations of Wernicke's encephalopathy. We discuss the possible mechanisms of fatal cardiovascular collapse and the unusual presentation of a case without a history of alcoholic intake or clinical malnutrition.

Gas exchange and pulmonary haemodynamic responses to fat emulsions in acute respiratory distress syndrome.

OBJECTIVE: To investigate the gas exchange and pulmonary haemodynamic responses to two different intravenous fat emulsions in patients with acute respiratory distress syndrome (ARDS). DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Intensive care unit in a university-affiliated hospital. PATIENTS: 21 patients with ARDS [mean age, 57 +/- 3 (SEM) years; Acute Physiology and Chronic Health Evaluation II, 20 +/- 3; Murray's score, 2.85 +/- 0.12] consecutively admitted. INTERVENTIONS: Patients were assigned to three groups (n = 7 each): group A (LCT) received long-chain triglycerides (20% LCT), group B (MCT/LCT), medium-chain triglycerides/long-chain triglycerides (20% MCT/LCT: 50/50) and group C placebo (0.9% sodium chloride, NaCl). The infusion was always given at the rate of 2 mg/kg min over a total period of 12 h, with a volume infusion of 500 ml in each group. MEASUREMENTS: Data were collected before, immediately after and 12 h after infusion ceased. Pulmonary and systemic haemodynamic and gas exchange variables were measured at each time point. Serum triglyceride cholesterol, and non-esterified fatty acids levels were measured. RESULTS: During LCT infusion, cardiac output, oxygen consumption and oxygen delivery increased (all p < 0.05), whereas pulmonary haemodynamics, arterial oxygen tension, mixed venous partial pressure of oxygen and venous admixture ratio remained essentially unaltered. No changes were observed following MCT/LCT infusion. CONCLUSIONS: The administration of LCT emulsion given at a slow rate did not alter arterial oxygenation because of the beneficial effect of a high cardiac output, hence offsetting the detrimental effect of increased O2 consumption.