Use of intraoperative high frequency oscillatory ventilation in neonates with pulmonary hypoplasia.

High-frequency oscillatory ventilation (HFOV) is a ventilatory modality widely used in neonatal intensive care units. Its main indication is restrictive lung pathology with difficult gas exchange using conventional mechanical ventilation (CMV). Patients receiving CMV require high intensity care, and immature lungs can be at risk for barotrauma and volutrauma. The few studies that have explored the use of HFOV in the operating room are mainly limited to HFVO during congenital diaphragmatic hernia repair. Limited experience of this ventilatory method in the operating room may be a disadvantage for the anesthesiologist. However, it is important to remember the benefits of this technique as a lung protection strategy. We report two cases of neonatal pulmonary hypoplasia of different etiology in which good oxygenation and ventilation was achieved with intraoperative HFOV.

Stratum Corneum Sampling to Assess Bioequivalence between Topical Acyclovir Products.

PURPOSE: To examine the potential of stratum corneum (SC) sampling via tape-stripping in humans to assess bioequivalence of topical acyclovir drug products, and to explore the potential value of alternative metrics of local skin bioavailability calculable from SC sampling experiments. METHODS: Three acyclovir creams were considered in two separate studies in which drug amounts in the SC after uptake and clearance periods were measured and used to assess bioequivalence. In each study, a "reference" formulation (evaluated twice) was compared to the "test" in 10 subjects. Each application site was replicated to achieve greater statistical power with fewer volunteers. RESULTS: SC sampling revealed similarities and differences between products consistent with results from other surrogate bioequivalence measures, including dermal open-flow microperfusion experiments. Further analysis of the tape-stripping data permitted acyclovir flux into the viable skin to be deduced and drug concentration in that 'compartment' to be estimated. CONCLUSIONS: Acyclovir quantities determined in the SC, following a single-time point uptake and clearance protocol, can be judiciously used both to objectively compare product performance in vivo and to assess delivery of the active into skin tissue below the barrier, thereby permitting local concentrations at or near to the site of action to be determined.

Development and characterisation of chondroitin sulfate- and hyaluronic acid-incorporated sorbitan ester nanoparticles as gene delivery systems.

Glycosaminoglycans (GAGs) are natural polymers that are broadly used in gene delivery systems to increase stability as well as decrease toxicity and nonspecific interactions, thereby increasing transfection efficiency. In this work, we propose sorbitan ester-based lipid nanoparticles (SENS) functionalised with the GAGs chondroitin sulfate (CS) and hyaluronic acid (HA) as gene delivery systems. For this purpose, we describe the design and evaluation of these nanosystems loaded with plasmid DNA, including an evaluation of their physicochemical characteristics, stability properties, ability to protect and efficiently transfect cells with Enhanced Green Fluorescent Protein plasmid (pEGFP) in vitro, and biocompatibility both in vitro and in vivo. We confirm that molecules with high biological value and targeting potential, such as HA and CS, can be successfully incorporated into our recently developed sorbitan ester-based nanoparticles (SENS) and that this incorporation leads to effective stabilisation of both nanosystems as well as protects plasmid DNA. We demonstrated that the aforementioned incorporation of HA and CS enables long-term stability of the nanosystems in both liquid and lyophilised states, which is a remarkable property that can aid in their transfer to industry. The ability of these functionalised nanosystems to transfect the A549 cell line without compromising cell viability was also shown, as well as their innocuous safety profile in vivo. Thus, we provide valuable evidence of the suitable properties and potential of these hybrid nanoparticles as gene delivery systems.

Topical bioavailability of diclofenac from locally-acting, dermatological formulations.

Assessment of the bioavailability of topically applied drugs designed to act within or beneath the skin is a challenging objective. A number of different, but potentially complementary, techniques are under evaluation. The objective of this work was to evaluate in vitro skin penetration and stratum corneum tape-stripping in vivo as tools with which to measure topical diclofenac bioavailability from three approved and commercialized products (two gels and one solution). Drug uptake into, and its subsequent clearance from, the stratum corneum of human volunteers was used to estimate the input rate of diclofenac into the viable skin layers. This flux was compared to that measured across excised porcine skin in conventional diffusion cells. Both techniques clearly demonstrated (a) the superiority in terms of drug delivery from the solution, and (b) that the two gels performed similarly. There was qualitative and, importantly, quantitative agreement between the in vitro and in vivo measurements of drug flux into and beyond the viable skin. Evidence is therefore presented to support an in vivo - in vitro correlation between methods to assess topical drug bioavailability. The potential value of the stratum corneum tape-stripping technique to quantify drug delivery into (epi)dermal and subcutaneous tissue beneath the barrier is demonstrated.

Influence of Fluorination on the Solubilities of Carbon Dioxide, Ethane, and Nitrogen in 1-n-Fluoro-alkyl-3-methylimidazolium Bis(n-fluoroalkylsulfonyl)amide Ionic Liquids.

The effect on gas solubilities of adding partially fluorinated alkyl side chains either on imidazolium-based cations or on bis(perfluoroalkylsulfonyl)amide anions was studied. The aim was to gain knowledge of the mechanisms of dissolution of gases in fluorinated ionic liquids and, if possible, to improve physical absorption of carbon dioxide in ionic liquids. We have determined experimentally, in the temperature range of 298-343 K and at pressures close to atmospheric pressure, the solubility and thermodynamics of solvation of carbon dioxide, ethane, and nitrogen in the ionic liquids 1-octyl-3-methylimidazolium bis[trifluoromethylsulfonyl]amide ([C8mim][NTf2]), 1-octyl-3-methylimidazolium bis[pentafluoroethylsulfonyl]amide ([C8mim][BETI]), 1-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-3-methylimidazolium bis[trifluoromethylsulfonyl]amide ([C8H4F13mim][NTf2]), and 1-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-3-methylimidazolium bis[pentafluoroethylsulfonyl]amide ([C8H4F13mim][BETI]). Ionic liquids with partial fluorination on the cation were found to exhibit higher carbon dioxide and nitrogen mole fraction solubilities but lower ethane solubilities, compared to those of their hydrogenated counterparts. Molecular simulation provided insights about the mechanisms of solvation of the different gases in the ionic liquids.

Characterization and comparison of two novel nanosystems associated with siRNA for cellular therapy.

To direct stem cell fate, a delicate control of gene expression through small interference RNA (siRNA) is emerging as a new and safe promising strategy. In this way, the expression of proteins hindering neuronal commitment may be transiently inhibited thus driving differentiation. Mesenchymal stem cells (MSC), which secrete tissue repair factors, possess immunomodulatory properties and may differentiate towards the neuronal lineage, are a promising cell source for cell therapy studies in the central nervous system. To better drive their neuronal commitment the repressor Element-1 silencing transcription (REST) factor, may be inhibited by siRNA technology. The design of novel nanoparticles (NP) capable of safely delivering nucleic acids is crucial in order to successfully develop this strategy. In this study we developed and characterized two different siRNA NP. On one hand, sorbitan monooleate (Span(®)80) based NP incorporating the cationic components poly-l-arginine or cationized pullulan, thus allowing the association of siRNA were designed. These NP presented a small size (205 nm) and a negative surface charge (-38 mV). On the other hand, lipid nanocapsules (LNC) associating polymers with lipids and allowing encapsulation of siRNA complexed with lipoplexes were also developed. Their size was of 82 nm with a positive surface charge of +7 mV. Both NP could be frozen with appropriate cryoprotectors. Cytotoxicity and transfection efficiency at different siRNA doses were monitored by evaluating REST expression. An inhibition of around 60% of REST expression was observed with both NP when associating 250 ng/mL of siRNA-REST, as recommended for commercial reagents. Span NP were less toxic for human MSCs than LNCs, but although both NP showed a similar inhibition of REST over time and the induction of neuronal commitment, LNC-siREST induced a higher expression of neuronal markers. Therefore, two different tailored siRNA NP offering great potential for human stem cell differentiation have been developed, encouraging the pursuit of further in vitro and in vivo in studies.

Anionic nanoparticles based on Span 80 as low-cost, simple and efficient non-viral gene-transfection systems.

The existing strategies in the design of non-viral vectors for gene therapy are primarily conceived for cationic systems. However, the safety concerns associated with the use of positively charged systems for nucleic acid delivery and several reports regarding the efficacy of negatively charged systems highlights the need for improved gene-delivery vectors. With these premises in mind, we investigated the development of new negatively charged nanoparticles based on Sorbitan esters (Span(®)) ­ extremely cheap excipients broadly used in the pharmaceutical industry ­ on the basis of a simple, one-step and easily scalable procedure. For their specific use in gene therapy, we have incorporated oleylamine (OA) or poly-L-arginine (PA) into these nanosystems. Thus, we used Sorbitan monooleate (Span(®) 80) to design Span(®) 80-oleylamine and Span(®) 80-poly-L-arginine nanosystems (SP-OA and SP-PA, respectively). These systems can associate with the model plasmid pEGFP-C3 and show mean particle sizes of 304 nm and 247 nm and surface charges of -13 mV and -17 mV, respectively. The nanoparticles developed were evaluated in terms of in vitro cell viability and transfection ability. Both systems exhibited an appropriate cell-toxicity profile and are able to transfect the plasmid effectively. Specifically, the nanosystems including OA among their components provided higher transfection levels than the SP-PA nanoparticles. In conclusion, anionic nanoparticles based on Span(®) 80 can be considered low-cost, simple and efficient non-viral anionic gene-transfection systems.

Absorption of carbon dioxide, nitrous oxide, ethane and nitrogen by 1-alkyl-3-methylimidazolium (C(n)mim, n = 2,4,6) tris(pentafluoroethyl)trifluorophosphate ionic liquids (eFAP).

We measured the densities of 1-alkyl-3-methylimidazolium (C(n)mim, n = 2,4,6) tris(pentafluoroethyl)trifluorophosphate ionic liquids (eFAP) as a function of temperature and pressure and their viscosities as a function of temperature. These ionic liquids are less viscous than those based in the same cations but with other anions such as bis(trifluoromethylsulfonyl)imide. The ionic liquids studied are only partially miscible with water, their solubility increasing with the size of the alkyl side-chain of the cation and with temperature (from x(H(2)O) = 0.20 ± 0.03 for [C(4)mim][eFAP] at 303.10 K to x(H(2)O) = 0.49 ± 0.07 for [C(6)mim][eFAP] at 315.10 K). The solubility of carbon dioxide, nitrous oxide, ethane, and nitrogen in the three ionic liquids was measured as a function of temperature and at pressures close to atmospheric. Carbon dioxide and nitrous oxide are the more soluble gases with mole fraction solubilities of the order of 3 × 10(-2) at 303 K. The solubility of these gases does not increase linearly with the size of the alkyl-side chain of the cation. The solubilities of ethane and nitrogen are much lower than those of carbon dioxide and nitrous oxide (mole fractions 60% and 90% lower, respectively). The higher solubility of CO(2) and N(2)O can be explained by more favorable interactions between the solutes and the polar region of the ionic liquids as shown by the enthalpies of solvation determined experimentally and by the calculation of the site-site solute-solvent radial distribution functions using molecular simulation.

[Spanish Society of Anaesthesia (SEDAR) guidelines for pre-anaesthesia checking procedures]. / Directrices de procedimientos de comprobación y validación («chequeo¼) previos a la anestesia de la Sociedad Española de Anestesiología.

We present this document as a guide to preparing a specific institutional pre-anaesthesia checklist, as recommended in the Helsinki declaration on patient safety in anaesthesiology. Also, the recently recommended WHO "safe surgery check-list" includes a check-list for anaesthesia. A working group was established in accordance with the charter of the Spanish Society of Anaesthesiology and Resuscitation (Sociedad Española de Anestesiología y Reanimación [SEDAR]). The new patient safety culture introduced into medicine, and the recommendations of European anaesthesia societies has led us to design and update protocols in order to improve results in this important part of our speciality. We have prepared these recommendations or guidelines using, as examples, updates of pre-anaesthesia check-lists by other American (ASA), British, or Canadian societies of anaesthesia. With that aim, we enlisted the help of anaesthesia ventilator experts and the participation and advice of experienced anaesthesiologists from all parts of Spain. After various corrections and modifications, the document was available at www.sedar.es, so that any anaesthesiologist could propose any correction, or give their opinion. Finally, these guidelines have been approved by the SEDAR Board of Directors, before it was sent for publication in this journal. The aims of this document are to provide: a guideline applicable to all anaesthesia machines, a descriptive pre-anaesthesia check-list that include everything necessary for the anaesthesia procedure, and a resumed check-list to be available in all the anaesthesia machines or other equivalent, but prepared for each institution, which should include anaesthetic equipment and drugs. So, in order to ensure the aims and requirements of the European Board of Anaesthesiology, the European Society of Anaesthesiology, and the WHO are met, each institution should have a protocol for checking equipment and drugs. These guidelines are applicable to any anaesthesia equipment, enabling every institution to develop their own checking protocols, adapted to their anaesthesia machines and their procedures. With the consent of the SEDAR, this group will collaborate with anaesthesia machines providers in order to develop specific checklists for each of their models that will be available at www.sedar.es.

[Anesthesia with propofol, remifentanil and cisatracurium in renal transplantation]. / Anestesia con propofol, remifentanilo y cisatracurio en un trasplante renal.

A 41-year-old woman with end-stage renal insufficiency in peritoneal dialysis for 3 years received a kidney transplant under anesthesia with remifentanil, propofol, and cisatracurium. She had a history of hypertension and was being treated with enalapril, metoprolol and erythropoietin. After anesthetic induction, blood pressure fell significantly and surgery was performed in a context of hemodynamic stability. The postoperative course was good, with a functional graft and adequate diuresis from the start. Anesthetics with minimal residual effects and as little renal toxicity as possible are ideal for use in kidney transplantation. The drugs used in this case had pharmacokinetic and pharmacodynamic properties that make them particularly appropriate for such patients.

Management of massive air leak following intubation injury in a very low birth weight infant.

Perforation of an infant's trachea after orotracheal intubation for general anaesthesia is a rarely described serious complication. This article reports an unusual case of laceration of the trachea in an 8-week-old infant with a history of prolonged neonatal intubation needed to treat hyaline membrane disease. After diagnosis the tracheal injury was managed conservatively. Factors involved in the occurrence of the injury and its management are discussed.

A simple technique to perform combined ultrafiltration.

To combine the advantages of conventional and modified ultrafiltration while keeping cardiopulmonary bypass technique simple, we have developed a simplified circuit of combined ultrafiltration, which is presently used in our pediatric patients. In addition to the benefits of combined ultrafiltration, this circuit allows the rewarming and prevention of heat loss in small children and neonates.

[Preloading with 500 ml of Hartmann's solution lessens the incidence and severity of hypotension and reduces the need for ephedrine after epidural anesthesia in ambulatory patients]. / La prehidratación con 500 ml de solución de Hartmann disminuye la incidencia e intensidad de la hipotensión y reduce las necesidades de efedrina tras anestesia epidural en pacientes ambulatorios.

INTRODUCTION: Fluid preloading to prevent hypotension after epidural anesthesia has been widely questioned, although few studies have been performed in outpatients. OBJECTIVE: To evaluate the incidence and severity of hypotension, and the need for vasoactive agents after epidural anesthesia in outpatients who did or did not receive fluid preloading. PATIENTS AND METHODS: Forty patients under 55 years of age (ASA I and II) undergoing general surgery on an outpatient basis were assigned randomly to two groups of 20 according to whether they were to receive loading with Hartmann's solution or not before epidural anesthesia. All received a similar epidural dose of 2% mepivacaine. Hypotension was defined as a decrease of 20% in systolic or mean blood pressure in comparison with baseline, or absolute pressures of < 90 and 60 mmHg, respectively. Hypotension was treated with 5 mg boluses of ephedrine. RESULTS: Fourteen patients in the non-preloading group and 5 in the preloading group developed hypotension (p < 0.05). Hypotensive episodes were fewer in patients receiving preloading fluids (0.5 +/- 1.2 versus 2.0 +/- 2.4; p < 0.05). The ephedrine dose required was higher in non-preloaded patients than in preloaded ones (10.0 +/- 12.2 versus 2.6 +/- 6.3 mg; p < 0.05). Time until presentation of hypotension was longer for non-preloaded patients. CONCLUSIONS: For patients undergoing outpatient surgery, fluid preloading with 500 ml of Hartman's solution decreases both the incidence and severity of hypotension, as well as the need for vasoactive drugs after epidural anesthesia.

[Prolonged neuromuscular block after a single dose of vecuronium in a patient with undiagnosed polyneuropathy and steroid myopathy]. / Bloqueo neuromuscular prolongado tras dosis única de vecuronio en un paciente con polineuropatía y miopatía esteroide no diagnosticadas.

We report the case of a patient who had been receiving long-term corticoid therapy with undiagnosed polyneuropathy and steroid-related myopathy before experiencing prolonged neuromuscular blockade (lasting longer than 4 hours) after administration of a single dose of 0.08 mg/kg of vecuronium. Neuromuscular function was monitored by accelerometry with four-stimuli series. Many of the circumstances present in this case -such as prior administration of succinylcholine, the use of an inhaled anesthetic, kidney insufficiency and cyclosporin therapy- have been associated with increased duration of blockade induced by neuromuscular blockers, although durations reported have been shorter than that experienced by our patient. After electromyography and muscle biopsy, polyneuropathy and steroid-related myopathy were diagnosed. We conclude that neuromuscular blockers should be administered with extreme caution to patients with polyneuropathy and those undergoing long-term corticoid therapy, in order to prevent prolonged neuromuscular blockade.

[Combined perioperative ultrafiltration in pediatric cardiac surgery. The preliminary results]. / Ultrafiltración combinada perioperatoria en cirugía cardíaca pediátrica. Resultados preliminares.

INTRODUCTION AND OBJECTIVES: Recently, ultrafiltration techniques are used more and more as a treatment for the inflammatory response of cardiopulmonary bypass. It also provides fine control of fluids. The purpose of this study is to present a technique which combines conventional and modified ultrafiltration and to analyze the obtained results. PATIENTS AND METHODS: 22 patients (mean weight 13.1 +/- 8.4 kg) operated on cardiopulmonary bypass. Combined ultrafiltration was performed during cardiopulmonary bypass (conventional) and after pump (modified ultrafiltration). We analyzed cardiopulmonary bypass variables, the first 24-hour hemodynamics, biological variables (arterial blood gases, cell counts, IL-6, adhesion molecules ICAM-1 and VCAM-1, and coagulation profiles). RESULTS: A total amount of 1,399 +/- 680 ml/m2 of mean combined ultrafiltrate volume was obtained (657 +/- 386 ml/m2 during cardiopulmonary bypass and 845 +/- 358 ml/m2 post-cardiopulmonary bypass). After modified ultrafiltration, hematocrit rose from 23 +/- 2.3 to 32 +/- 4.1, arterial systolic blood pressure rose from 74 +/- 13 to 98 +/- 20 mmHg, heart rate decreased from 133 +/- 22 to 126 +/- 23 bpm, and central versus pressure did not change. A statistically significant relationship (multivariable), was shown between modified ultrafiltration time and VCAM-1 post-ultrafiltration levels. Platelet count was lower and diuresis rose related to cardiopulmonary bypass ultrafiltration volume and diuresis increased. CONCLUSIONS: Perioperative combined ultrafiltration is feasible without undue morbidity and provides adequate hemoconcentration and excellent postoperative hemodynamic results. More studies with control groups are necessary to better define the therapeutic influence in antiinflammatory properties of this technique.

[Comparison of sevoflurane and propofol in the maintenance of and recovery from anesthesia]. / Comparación entre sevoflurano y propofol en el mantenimiento y recuperación de la anestesia.

OBJECTIVE: To compare the recovery of patients after anesthesia with sevoflurane or propofol during open urological surgery or lumbar column surgery of intermediate duration. PATIENTS AND METHODS: Thirty-six ASA I, II or II patients were enrolled prospectively and randomly assigned to two groups to receive either sevoflurane (n = 19) or proporol (n = 17). Anesthetic induction was accomplished with thiopental, fentanil and vecuronium. During anesthetic maintenance a mixture of 60% nitrous oxide in oxygen plus the drug under study was adjusted to keep blood pressure and/or heart rate within +/- 20% of baseline. After surgery we recorded time until eye opening, spontaneous breathing, extubation, orientation, and identification of parts of the body. Side effects were likewise recorded. In the postanesthetic recovery ward patient condition was assessed using the Aldrete scale, the Newman-Trieger test and a visual analog scale for postoperative pain. Consumption of analgesic during the first 24 h after surgery was monitored. RESULTS: No significant differences were found in demographic data; duration of anesthesia; anesthetic doses; or time until spontaneous breathing, extubation, orientation or identification of parts of the body. Only time until eye opening was shorter in the sevoflurane group than in the propofol group (6.9 +/- 3.3 vs 11.5 +/- 4.8 min; p < 0.05). No differences were recorded on scales reflecting intermediate-term recovery. Analgesic consumption and the incidence of side effects were similar in both groups. CONCLUSIONS: Sevoflurane and propofol are comparable for anesthetic maintenance in urological and neurological procedures of intermediate duration.

[Cortical blindess as symptom of pre-eclampsia]. / Ceguera cortical como síntoma de presentación de una preeclampsia.

Neurological complications during preeclampsia are not infrequent; the appearance of total blindness is rare, however. We report the case of a 32-year-old primipara with no outstanding history, who presented total loss of vision with no accompanying neurological symptoms during week 37 of the pregnancy. Effective early management of blood pressure to levels at which self-regulation of cerebral perfusion could be established allowed total recovery of vision 8 hours after admission to the intensive care recovery ward. Cranial computerized axial tomography (CAT) showed bilateral occipital subcortical edema that resolved after 8 days. The patient was released 13 days after admission with no sequelae.

[Pulmonary edema of neurogenic origin and transtentorial hernia during anesthesia induction in a child with ventriculoperitoneal shunt]. / Edema pulmonar de origen neurogénico y herniación transtentorial durante la inducción anestésica en un niño con derivación ventriculoperitoneal.

We report the case of a 12-year-old boy with a peritoneal ventricular shunt who developed acute pulmonary edema of neurogenic origin after laryngoscopy and orotracheal intubation. Such maneuvers in the presence of diminished intracranial distensibility caused transtentorial herniation. Delayed diagnosis led to death in spite of appropriate treatment of postoperative complications.