Juan Guardiola

Hypercoagulability in patients with obstructive sleep apnea

BACKGROUND Obstructive sleep apnea (OSA) has been linked to cardiovascular complications such as stroke and myocardial infarction. Previous studies demonstrate that OSA patients show elevated fibrinogen levels and increased platelet aggregation that are reversed with 1 night of nasal continuous positive airway pressure treatment (NCPAP). Questioning overall coagulability in OSA, we examined whole blood coagulability in 11 chronically NCPAP treated OSA subjects, 22 previously untreated OSA subjects, and in 16 of these after 1 night of NCPAP treatment. PATIENTS AND METHODS During full polysomnography, subjects from each group had blood drawn prior to bedtime (21:00 h) and upon waking in the morning (07:00 h). RESULTS Untreated OSA patients had faster P.M. clotting times than chronically treated OSA patients (3.33+/-0.31 versus 6.12+/- 0.66 min, P<0.05 by ANOVA). A.M. values showed similar results (4.31+/- 0.34 min versus 7.08+/-0.52 min, P<0.05 by ANOVA) for the respective groups. One overnight treatment with nasal CPAP did not produce a significant change in A.M. whole blood coagulability (4.35 +/-0.43 to 5.31+/-0.53 min; n=16; P=0.1) in 16 treated subjects. CONCLUSIONS These data indicate a relationship between obstructive sleep apnea and blood hypercoagulability status that appears to be reversed by chronic NCPAP treatment. These data suggest that NCPAP might protect against the development of cardiovascular complications in OSA patients.

Predicting mortality in hospitalized patients with 2009 H1N1 influenza pneumonia.

BACKGROUND Community-acquired pneumonia (CAP) severity scores can identify patients at low risk for mortality who may be suitable for ambulatory care. Here, we follow the clinical course of hospitalized patients with CAP due to 2009 H1N1 influenza. OBJECTIVE To evaluate the role of CAP severity scores as predictors of mortality. METHODS This was a secondary data analysis of patients hospitalized with CAP due to 2009 H1N1 influenza confirmed by reverse transcriptase polymerase chain reaction enrolled in the CAPO (Community-Acquired Pneumonia Organization) international cohort study. CAP severity scores PSI (Pneumonia Severity Index), CURB-65 (confusion, urea, respiratory rate, blood pressure, age ≥ 65 years) and CRB-65 (confusion, respiratory rate, blood pressure, age ≥ 65 years) were calculated. Actual and predicted mortality rates were compared. A total of 37 predictor variables were evaluated to define those associated with mortality. RESULTS Data from 250 patients with CAP due to 2009 H1N1 influenza were analyzed. Patients with low predicted mortality rates (0-1.5%) had actual mortality rates ranging from 2.6% to 17.5%. Obesity and wheezing were the only novel variables associated with mortality. CONCLUSIONS The decision to hospitalize a patient with CAP due to 2009 H1N1 influenza should not be based on current CAP severity scores, as they underestimate mortality rates in a significant number of patients. Patients with obesity or wheezing should be considered at an increased risk for mortality.

Generation of Oxidants by Hypoxic Human Pulmonary and Coronary Smooth-Muscle Cells

BACKGROUND Pulmonary vasoconstriction in response to hypoxia is unusual inasmuch as local exposure of nonpulmonary vasculature to hypoxia results in vasodilation. It has been suggested that pulmonary artery smooth-muscle cells may relax in response to intracellular generation of reactive oxygen species (ROS) and that the production of ROS decreases under hypoxia. However, other workers report increased ROS production in human pulmonary artery smooth-muscle cells (HPASMC) during hypoxia. METHODS Using dihydrodichlorofluorescein diacetate, dihydroethidium, and Amplex Red (Molecular Probes; Eugene, OR), we estimated ROS generation by confluent primary cultures of HPASMC and human coronary artery smooth-muscle cells (HCASMC) under normoxia (20%) and acute hypoxia (5%). RESULTS All three assay systems showed that HPASMC production of ROS is decreased under hypoxia and to a greater extent than the decrease in ROS production by HCASMC. A substantially greater percentage of normoxic ROS production by HPASMC is mitochondrial (> 60%) compared to HCASMC (< 30%). CONCLUSIONS These results support the conclusion that ROS generation decreases, rather than increases, in HPASMC during hypoxia. However, as ROS production also decreases in HCASMC during hypoxia, the reason for the opposite change in vascular tone is not yet apparent.

Neumonía asociada a ventilación mecánica: riesgos, problemas y nuevos conceptos

La neumonia asociada a la intubacion y ventilacion mecanica es una complicacion que presenta una elevada incidencia y morbimortalidad, con unas caracteristicas muy particulares que la distinguen de la neumonia nosocomial en pacientes no intubados. Ademas, la inquietud que ello causa en el clinico, unido a las dificultades diagnosticas que plantea, motiva a menudo, entre otras consecuencias, unas decisiones terapeuticas muchas veces desproporcionadas que se ha demostrado comportan la genesis de resistencias bacterianas. De ahi el interes de realizar la presente revision sobre la fisiopatologia, el diagnostico y la estrategia terapeutica de este tipo de neumonia, en la que no faltan elementos de controversia en la bibliografia.

Neuroimmune Interaction in Inflammatory Diseases

The inflammatory response is modulated through interactions among the nervous, endocrine, and immune systems. Intercommunication between immune cells and the autonomic nervous system is a growing area of interest. Spatial and temporal information about inflammatory processes is relayed to the central nervous system (CNS) where neuroimmune modulation serves to control the extent and intensity of the inflammation. Over the past few decades, research has revealed various routes by which the nervous system and the immune system communicate. The CNS regulates the immune system via hormonal and neuronal pathways, including the sympathetic and parasympathetic nerves. The immune system signals the CNS through cytokines that act both centrally and peripherally. This review aims to introduce the concept of neuroimmune interaction and discuss its potential clinical application, in an attempt to broaden the awareness of this rapidly evolving area and open up new avenues that may aid in the treatment of inflammatory diseases.

Discrepancy between clinical criteria for diagnosing acute respiratory distress syndrome secondary to community acquired pneumonia with autopsy findings of diffuse alveolar damage

Diffuse alveolar damage (DAD) is the underlying pathological finding in most cases of acute respiratory distress syndrome (ARDS). The objective of this study was to compare clinical criteria for ARDS secondary to community acquired pneumonia with autopsy findings of DAD and to determine the discrepancy rate between the two. We compared prospectively obtained clinical diagnosis of ARDS secondary to community acquired pneumonia with autopsy findings of DAD and pneumonia. Forty nine patients dead with a clinical diagnosis of ARDS secondary to pneumonia who underwent autopsy between 1986 and 2004 in our ICU were included with systematic histopathological analysis of all lung lobes. The discrepancy rate between the premortem clinical diagnosis of ARDS secondary to pneumonia and DAD at autopsy was determined. Seven patients were found to have neither infection nor DAD at autopsy. Six patients showed pathologic signs of DAD without evidence of infection. Out of 38 patients meeting clinical criteria for ARDS secondary to pneumonia and proven pneumonia at autopsy, 25 met criteria for DAD at autopsy. Therefore, 18 out of 49 patients who were clinically diagnosed with ARDS did not actually show pathological signs of DAD, resulting in a discrepancy rate of 37%. Despite an acceptable correspondence between clinical criteria for ARDS secondary to pneumonia and autopsy findings of DAD a significant number of patients had neither signs of DAD nor infection.

Estudio sobre la correlación clínico-patológica en el síndrome de distrés respiratorio agudo secundario

OBJECTIVE This study has aimed to study the clinicopathological correlation of patients with secondary acute respiratory distress syndrome (ARDS), specifically having extrapulmonary causes. SETTING A 22 beds intensive care unit. DESIGN An observational study of case series. PATIENTS Seventeen patients whose death was caused by acute respiratory distress syndrome were included. INTERVENTION A systematic histopathological study was made of all the pulmonary lobes of patients who died in our ICU with the clinical diagnosis of secondary ARDS, who had undergone an autopsy between 1999 and 2009. The Kappa analysis was used to analyze the grade of correlation between the clinical and the pathological diagnosis. RESULTS The autopsy confirmed to cases of false positive in 17 patients with ARDS (11%). The kappa value was 0.77, so that the concordance analysis was considered to be satisfactory. CONCLUSIONS The clinical criteria for ARDS correlate well with acute alveolar damage (AAD) in the autopsy study in patients with secondary ARDS, although some false positive cases can be observed.

ARACHIDONIC ACID PRODUCTS IN AIRWAY NOCICEPTOR ACTIVATION DURING ACUTE LUNG INJURY

We have reported that airway nociceptors [C fibre receptors (CFRs) and high‐threshold Aδ fibre receptors (HTARs)] are activated during oleic acid (OA)‐induced acute lung injury. In the present studies, we tested the hypothesis that this nociceptor activation is mediated by arachidonic acid products. In anaesthetized, open‐chest, mechanically ventilated rabbits, we examined the response of the nociceptors to intravenous injection of OA before and after blocking the cyclo‐oxygenase pathways with indomethacin. Pretreatment with indomethacin (20 mg kg−1) decreased the background activities of both CFRs (from 0.48 ± 0.12 to 0.25 ± 0.08 impulses/s, n= 7, P < 0.05) and HTARs (from 0.54 ± 0.14 to 0.23 ± 0.08 impulses/s, n= 10, P < 0.01). It also blocked the response of the nociceptors to OA. Likewise, pretreatment with thromboxane synthase inhibitor (ketoconazole) also blocked the nociceptor response to OA. In addition, local microinjection or intravenous injection of a thromboxane mimetic stimulated CFRs and HTARs. The present results clearly indicate that arachidonic acid metabolites mediate airway nociceptor activation during OA‐induced acute lung injury and suggest that thromboxane may be a key mediator.

Opposite responses to lidocaine between intrapulmonary mechanical and chemical sensors

We attempted to determine whether intrapulmonary sensory receptors are nourished by the pulmonary or the systemic circulation. Single-unit activity from the cervical vagus nerve was recorded in anesthetized, open chest, mechanically ventilated rabbits, comparing responses to right or left ventricular injection of 2% lidocaine (at 4 mg/kg). Airway mechanosensors [slowly adapting receptor (SARs) and rapidly adapting receptors] were inhibited by lidocaine, whereas chemosensors (C-fiber receptors and high-threshold A delta-receptors) were stimulated. Furthermore, all types of airway sensors were perfused preferentially by the pulmonary circulation. For example, 14 of the 15 tested SARs ceased discharge at 4.1 +/- 0.6 s after lidocaine injection into the right ventricle. The blocking effect lasted 35 +/- 6.2 s. In contrast, none of the 15 SARs ceased their activity after lidocaine injection into the left ventricle. Our data show that intrapulmonary sensors are mainly nourished by the pulmonary circulation. Their very short latency indicates that these sensors receive ample blood supply. Thus, intrapulmonary sensors rely on the pulmonary circulation to detect bioactive agents in the blood.

Enteral nutrition as stress ulcer prophylaxis in critically ill patients: A randomized controlled exploratory study

Purpose: We investigated whether early enteral nutrition alone may be sufficient prophylaxis against stress‐related gastrointestinal (GI) bleeding in mechanically ventilated patients. Materials and methods: Prospective, double blind, randomized, placebo‐controlled, exploratory study that included mechanically ventilated patients in medical ICUs of two academic hospitals. Intravenous pantoprazole and early enteral nutrition were compared to placebo and early enteral nutrition as stress‐ulcer prophylaxis. The incidences of clinically significant and overt GI bleeding were compared in the two groups. Results: 124 patients were enrolled in the study. After exclusion of 22 patients, 102 patients were included in analysis: 55 patients in the treatment group and 47 patients in the placebo group. Two patients (one from each group) showed signs of overt GI bleeding (overall incidence 1.96%), and both patients experienced a drop of >3 points in hematocrit in a 24‐hour period indicating a clinically significant GI bleed. There was no statistical significant difference in the incidence of overt or significant GI bleeding between groups (p = 0.99). Conclusion: We found no benefit when pantoprazole is added to early enteral nutrition in mechanically ventilated critically ill patients. The routine prescription of acid‐suppressive therapy in critically ill patients who tolerate early enteral nutrition warrants further evaluation. Highlights:GI bleeding has low incidence in the critically ill mechanically ventilated patients.Adding PPI to enteral nutrition may not offer an added prophylaxis against stress‐related GI bleeding.Our study supports the protective role of enteral nutrition in ICU.