High-flow nasal cannula therapy, factors affecting effective inspired oxygen fraction: an experimental adult bench model.

Oxygenation through High Flow Delivery Systems (HFO) is described as capable of delivering accurate FiO2. Meanwhile, peak inspiratory flow [Formula: see text] ) of patients with acute hypoxemic respiratory failure can reach up to 120 L/min, largely exceeding HFO flow. Currently, very few data on the reliability of HFO devices at these high [Formula: see text] are available. We sought to evaluate factors affecting oxygenation while using HFO systems at high [Formula: see text] in a bench study. Spontaneous breathing was generated with a mechanical test lung connected to a mechanical ventilator Servo-i®, set to volume control mode. Gas flow from a HFO device was delivered to the test lung. The influence on effective inspired oxygen fraction of three parameters (FiO2 0.6, 0.8, and 1, [Formula: see text] from 28 to 98.1 L/min, and HFO Gas Flows from 40 to 60 L/min) were analyzed and are reported. The present bench study demonstrates that during HFO treatment, measured FiO2 in the lung does not equal set FiO2 on the device. The substance of this variation (ΔFiO2) is tightly correlated to [Formula: see text] (Pearson's coefficient of 0.94, p-value < 0.001). Additionally, set FiO2 and Flow at HFO device appear to significatively affect ΔFiO2 as well (p-values < 0.001, adjusted to [Formula: see text] ). The result of multivariate linear regression indicates predictors ([Formula: see text] , Flow and set FiO2) to explain 92% of the variance of delta FiO2 through K-Fold Cross Validation. Moreover, adjunction of a dead space in the breathing circuit significantly decreased ΔFiO2 (p < 0.01). The present bench study did expose a weakness of HFO devices in reliability of delivering accurate FIO2 at high [Formula: see text] as well as, to a lesser extent, at [Formula: see text] below equivalent set HFO Flows. Moreover, set HFO flow and set FIO2 did influence the variability of effective inspired oxygen fraction. The adjunction of a dead space in the experimental set-up significantly amended this variability and should thus be further studied in order to improve success rate of HFO therapy.

Refractory hypercapnia: a simplified technique for extracorporeal CO2 removal (ECCO2R) in the presence of therapeutic limitations.

Refractory hypercapnia with severe acidosis appeared in a 67-year-old man who presented with lung fibrosis and a left pneumothorax as delayed complications of bleomycin chemotherapy for advanced grade lymphoma. Due to failure of noninvasive ventilation using a high-flow nasal cannula oxygen system, the patient was mechanically ventilated with two ventilators at different settings, after intubation with a double-lumen tube. As he had a poor haematological prognosis, extracorporeal membranous oxygenation was not considered. To remove some amount of carbon dioxide, we used a simplified method based on a veno-venous hemofiltration circuit coupled to a paediatric oxygenator and an air/oxygen blender. The efficacy on carbon dioxide removal was modest, with a percentage of CO2 total extraction ranging from 10.5 to 20.4%, but the system was immediately available, well tolerated and not very expensive.

Locked-in syndrome as an unusual complication of acute otitis media.

BACKGROUND: A 32-year-old woman developed altered consciousness two days after initial symptoms of acute otitis media, with purulent discharge from the right ear. She was quadriplegic, with spontaneous eye opening, mild neck stiffness, and lacking vestibular-ocular reflexes. METHODOLOGY: Upon admission, the patient was subjected to brain computed tomography (CT), magnetic resonance imaging (MRI), and lumbar puncture. RESULTS: CT was consistent with pansinusitis, right middle ear otitis, mastoiditis, and sphenoiditis. No brainstem lesion was evident; brain MRI demonstrated ischemic and secondary hemorrhagic lesions in the pons and cerebral peduncles. The dura mater in the petroclival space was intensely inflamed, and likely responsible for reduced basilar arterial blood flow. Lumbar puncture yielded clear cerebrospinal fluid; gram stain examination was negative and culture remained sterile. Streptococcus pneumoniae and Haemophilus influenzae were cultured from the purulent ear discharge. CONCLUSION: The final diagnosis was locked-in syndrome consecutive to inflammatory changes compressing the basilar artery.

Toll-like receptor 4 modulation as a strategy to treat sepsis.

Despite a decrease in mortality over the last decade, sepsis remains the tenth leading causes of death in western countries and one of the most common cause of death in intensive care units. The recent discovery of Toll-like receptors and their downstream signalling pathways allowed us to better understand the pathophysiology of sepsis-related disorders. Particular attention has been paid to Toll-like receptor 4, the receptor for Gram-negative bacteria outer membrane lipopolysaccharide or endotoxin. Since most of the clinical trial targeting single inflammatory cytokine in the treatment of sepsis failed, therapeutic targeting of Toll-like receptor 4, because of its central role, looks promising. The purpose of this paper is to focus on the recent data of various drugs targeting TLR4 expression and pathway and their potential role as adjunctive therapy in severe sepsis and septic shock.

Adjunctive therapies for severe sepsis.

Severe sepsis-associated mortality may still be improved by earlier recognition, faster and adequate source control, and targeted resuscitation. Patients who may benefit from the administration of drotrecogin alfa (activated) are currently those at high risk of death, and other indications should be better defined by ongoing trials. Use of low-dose steroids for the treatment of severe sepsis must be re-clarified by new studies and should be restricted to patients with refractory septic shock. Trials exploring the role of natural anticoagulants and Toll-like receptor inhibitors are ongoing and should be completed in the coming 3 years. Future trials in severe sepsis should target more homogeneous populations with a well-defined focus of infection and severity, receiving appropriate standard of care, and the tested intervention should be administered in a timely fashion according to the expected host response.

Non-heart-beating donor, 10-year experience in a Belgian transplant center.

All over the world, transplant teams are looking for ways to increase and improve the donor pool. Non-heart-beating donation may increase the number of donors, even if some technical, logistical, and emotional problems are still encountered. The results obtained by our team should stimulate other centers to implement this kind of donation in their hospitals. Herein we have described our experience with non-heart-beating donation.

Drug-drug interactions in the intensive care unit: Do they really matter?

PURPOSE: To describe prevalence and patterns of potential drug-drug interactions (pDDIs) in the intensive care unit (ICU), occurrence of adverse drug events (ADEs), and agreement between different compendia and intensivists' perceptions. METHODS: A cross-sectional study. Drug profiles of all adult patients from 2 academic ICUs were screened on day 3 upon admission. We identified pDDIs using 3 compendia (Stockley's, Micromedex, and Epocrates) and documented their mechanism of action, clinical consequences, severity, level of evidence, and management. Medical records were searched to identify ADEs potentially related to major pDDIs. Agreement between information sources (compendia, intensivists) was evaluated. RESULTS: We identified 1120 pDDIs among 275 patients. Median number of pDDIs per patient was 3.0 (interquartile range, 1-6), with 79% of patients presenting with at least 1 pDDI. Major pDDIs were detected in 18% of patients, with potentially related to ADEs in 4% of patients. Only 13% of all pDDIs were documented simultaneously in all 3 compendia. Different information sources (compendia, clinicians) showed "no" to "fair" agreement. CONCLUSIONS: Potential drug-drug interactions occurred in most ICU patients, contrasting with low rates of potentially related ADEs, which may have been underestimated. Sources of information are inconsistent, challenging the identification of pDDIs.

Surveillance of hospital-acquired infections in an intensive care department-the benefit of the full-time presence of an infection control nurse.

In the 42-bed intensive care department of a teaching hospital, the creation of a full-time infection control nurse post was followed by a 42% reduction in device-related hospital-acquired infection rates over a period of three years, and 33% reduction over a period of five years. Permanent surveillance accompanied by revision of procedures and bedside teaching were key factors in the improvement of quality of care. In the specific setting of an intensive care department, this study validates the previous conclusions reached in the SENIC study and emphasizes the essential role played by the infection control nurse in the care of critically ill patients.

Nicotine exposure alters in vivo human responses to endotoxin.

The alpha 7 nicotinic receptor is reportedly a key element in the cholinergic anti-inflammatory pathway. Because a prototypical ligand for this receptor is nicotine, we studied the in vivo human response to bacterial endotoxin or lipopolysaccharide (LPS) in the context of nicotine or placebo pretreatment. Twelve adult male normal subjects were studied prospectively. Six received overnight transcutaneous nicotine administration by application of a standard patch (7 mg). Six hours later, all subjects were given an intravenous dose of endotoxin (2 ng/kg) and were evaluated for an additional 24 h for circulating levels of inflammatory biomarkers, vital signs and symptoms. The nicotine subjects had elevated blood levels of the nicotine metabolite, continine, prior to and throughout the 24-h post-endotoxin exposure phase. Subjects receiving nicotine exhibited a significantly lower temperature response as well as attenuated cardiovascular responses for 2.5-6 h after LPS exposure. In addition, increased circulating interkeukin (IL)-10 and cortisol levels were also noted in nicotine subjects. These data indicate an alteration in LPS-induced systemic inflammatory responses in normal subjects exposed to transcutaneous nicotine. In this model of abbreviated inflammation, nicotine exposure attenuates the febrile response to LPS and promotes a more prominent anti-inflammatory phenotype.

Expression of tumour necrosis factor receptor and Toll-like receptor 2 and 4 on peripheral blood leucocytes of human volunteers after endotoxin challenge: a comparison of flow cytometric light scatter and immunofluorescence gating.

Toll-like receptors (TLRs) are involved in the recognition of bacterial products and thus participate in the induction of the inflammatory cascade. However, much less is known about the evolution of leucocyte TLR expression during human inflammatory stress. We hypothesized that a decrease in leucocyte TLRs could account for the so-called tolerance or hyporesponsiveness state to subsequent stimulation with bacteria-derived products. Because of the profound monocytopenia that ensues after in vivo lipopolysaccharide (LPS) challenge, we also compared monocyte TLR expression using two different techniques of flow cytometric gating. In a first set of experiments, 17 healthy volunteers underwent LPS challenge. Blood was drawn at different time-points and analysed by flow cytometry using light scatter gating and one-colour analysis to assess the expression of the tumour necrosis factor receptor (TNFR) and TLR2 and TLR4 on both monocytes and granulocytes. In a second set of experiments, the assessment of those receptors was made using a more specific gating method that utilized light scatter and CD14 immunofluorescence in a two-colour analysis. This was performed using whole blood drawn from five healthy volunteers and incubated ex vivo for different time periods with or without LPS and in 12 volunteers who underwent LPS challenge in vivo. The pattern of expression for monocyte TNFR was similar for both types of gating. Using only the light scatter gating, an initial drop of TLR 2 and 4 was observed on monocytes. By contrast, when using light scatter x immunofluorescence gating, an up-regulation of these two receptors following both in vivo and in vitro LPS exposure was observed. LPS up-regulates the expression of TLRs on monocytes and granulocytes. Depending upon the methodology utilized, contrasting results were obtained with respect to TLR2 and TLR4 expression. The flow cytometric gating technique used is of importance in determining cellular TLR2 and TLR4 expression, especially in blood samples exhibiting significant monocytopenia.

An unusual cause of abdominal pain.

A 36-year-old woman presented to the Emergency Room because of abdominal pain associated with hematuria and red blood blending to stool. On admission, the physical examination revealed abdominal tenderness and diffuse cutaneous hematoma. The laboratory findings showed abnormal clotting tests with high International Normalised Ratio (INR) and prolonged activated partial thromboplastin time. Hemoperitoneum and ureteral hematoma were noted on the abdomen computed tomography. The patient confessed she had ingested difenacoum for several weeks. All the symptoms resolved with fresh frozen plasma perfusion and vitamin K.