Susceptibility of two different PCA pumps to inaccurate delivery associated with pole position at low flow-rates in a pediatric setting - an experimental study.

PURPOSE: Vertical displacement of infusion pumps used in patient-controlled analgesia can cause irregularities in drug delivery and is especially crucial at low flow rates, which are commonly used in pediatrics. There is only scarce data available regarding the extent of these inaccuracies. The current in vitro study therefore aimed at a comparison of the performance of two commonly used PCA pumps at different pole positions due to vertical displacement. METHODS: The Syramed® µSP6000 Chroma syringe infusion pump featuring a stepper motor drive was compared to the CADD®-Solis pump utilizing a linear peristaltic pump system at two different flow rates (0.3 ml/h and 1 ml/h) and three different levels of height (0, + 50 and - 50 cm). Flow patterns and delivered volumes were measured after every change in position and infusion boluses, retrograde aspiration volumes and zero-drug delivery time were calculated. RESULTS: The Syramed® pump was more susceptible to vertical displacement than the CADD®-Solis pump and showed overall greater inaccuracies in the delivered volumes as well as higher infusion boluses, retrograde aspiration volumes and zero-drug delivery time at both flow rates. CONCLUSION: The observed differences between the pumps might be explained by the higher compliance of this syringe pump and the diverse working mechanisms. Overall, the CADD®-Solis pump might be considered a preferable option for patient-controlled analgesia in children. It is nonetheless essential for medical staff to be aware of the effects of vertical displacement of PCA pumps and to minimize these displacements as much as possible.

Effect of vertical stopcock position on start-up fluid delivery in syringe pumps used for microinfusions.

The purpose of this in vitro study was to evaluate the impact of the vertical level of the stopcock connecting the infusion line to the central venous catheter on start-up fluid delivery in microinfusions. Start-up fluid delivery was measured under standardized conditions with the syringe outlet and liquid flow sensors positioned at heart level (0 cm) and exposed to a simulated CVP of 10 mmHg at a set flow rate of 1 ml/h. Flow and intraluminal pressures were measured with the infusion line connected to the stopcock primarily placed at vertical levels of 0 cm, + 30 cm and - 30 cm or primarily placed at 0 cm and secondarily, after connecting the infusion line, displaced to + 30 cm and - 30 cm. Start-up fluid delivery 10 s after opening the stopcock placed at zero level and after opening the stopcock primarily connected at zero level and secondary displaced to vertical levels of + 30 cm and - 30 cm were similar (- 10.52 [- 13.85 to - 7.19] µL; - 8.84 [- 12.34 to - 5.33] µL and - 11.19 [- 13.71 to - 8.67] µL (p = 0.469)). Fluid delivered at 360 s related to 65% (zero level), 71% (+ 30 cm) and 67% (- 30 cm) of calculated infusion volume (p = 0.395). Start-up fluid delivery with the stopcock primarily placed at + 30 cm and - 30 cm resulted in large anterograde and retrograde fluid volumes of 34.39 [33.43 to 35.34] µL and - 24.90 [- 27.79 to - 22.01] µL at 10 s, respectively (p < 0.0001). Fluid delivered with the stopcock primarily placed at + 30 cm and - 30 cm resulted in 140% and 35% of calculated volume at 360 s, respectively (p < 0.0001). Syringe infusion pumps should ideally be connected to the stopcock positioned at heart level in order to minimize the amounts of anterograde and retrograde fluid volumes after opening of the stopcock.

Pressure-adjusted venting eliminates start-up delays and compensates for vertical position of syringe infusion pumps used for microinfusion.

Microinfusions are commonly used for the administration of catecholamines, but start-up delays pose a problem for reliable and timely drug delivery. Recent findings show that venting of the syringe infusion pump with draining of fluid to ambient pressure before directing the flow towards the central venous catheter does not counteract start-up delays. With the aim to reduce start-up delays, this study compared fluid delivery during start-up of syringe infusion pumps without venting, with ambient pressure venting, and with central venous pressure (CVP)-adjusted venting. Start-up fluid delivery from syringe pumps using a microinfusion of 1 mL/h was assessed by means of liquid flow measurement at 10, 60, 180 and 360 s after opening the stopcock and starting the pump. Assessments were performed using no venting, ambient pressure venting or CVP-adjusted venting, with the pump placed either at zero, - 43 cm or + 43 cm level and exposed to a simulated CVP of 10 mmHg. Measured fluid delivery was closest to the calculated fluid delivery for CVP-adjusted venting (87% to 100% at the different timepoints). The largest deviations were found for ambient pressure venting (- 1151% to + 82%). At 360 s after start-up 72% to 92% of expected fluid volumes were delivered without venting, 46% to 82% with ambient pressure venting and 96% to 99% with CVP-adjusted venting. CVP-adjusted venting demonstrated consistent results across vertical pump placements (p = 0.485), whereas the other methods had significant variances (p < 0.001 for both). In conclusion, CVP-adjusted venting effectively eliminates imprecise drug delivery and start-up delays when using microinfusions.

Association between Intraoperative Blood Transfusion, Regional Anesthesia and Outcome after Pediatric Tumor Surgery for Nephroblastoma.

BACKGROUND: Recent data suggest that anesthesiologic interventions-e.g., the choice of the anesthetic regimen or the administration of blood products-might play a major role in determining outcome after tumor surgery. In contrast to adult patients, only limited data are available regarding the potential association of anesthesia and outcome in pediatric cancer patients. METHODS: A retrospective multicenter study assessing data from pediatric patients (0-18 years of age) undergoing surgery for nephroblastoma between 2004 and 2018 was conducted at three academic centers in Europe. Overall and recurrence-free survival were the primary outcomes of the study and were evaluated for a potential impact of intraoperative administration of erythrocyte concentrates, the use of regional anesthesia and the choice of the anesthetic regimen. The length of stay on the intensive care unit, the time to hospital discharge after surgery and blood neutrophil-to-lymphocyte ratio were defined as secondary outcomes. RESULTS: In total, data from 65 patients were analyzed. Intraoperative administration of erythrocyte concentrates was associated with a reduction in recurrence-free survival (hazard ratio (HR) 7.59, 95% confidence interval (CI) 1.36-42.2, p = 0.004), whereas overall survival (HR 5.37, 95% CI 0.42-68.4, p = 0.124) was not affected. The use of regional anesthesia and the choice of anesthetic used for maintenance of anesthesia did not demonstrate an effect on the primary outcomes. It was, however, associated with fewer ICU transfers, a shortened time to discharge and a decreased postoperative neutrophil-to-lymphocyte ratio. CONCLUSIONS: The current study provides the first evidence for a possible association between blood transfusion as well as anesthesiologic interventions and outcome after pediatric cancer surgery.

Dimensional compatibility of rigid ventilating bronchoscopes with pediatric airway anatomy using different recommendations for age-related sizing-A bench study.

BACKGROUND: Appropriate size selection of pediatric rigid bronchoscopes is fundamental to avoidance of airway trauma and to a high success rate with the first intubation attempt. The aim of the present study was to compare the outer diameters of pediatric rigid bronchoscopes with the anatomical data on the pediatric airway. METHODS: Outer diameters (OD) of pediatric rigid ventilating bronchoscopes as given by the manufacturer were compared with published computed tomography internal diameters (ID) of the cricoid outlet, the trachea as well as the left and right proximal mainstem bronchus, using six published recommendations for age-related size selection. The ratios between a specific OD and ID were calculated and given as percentage values (%) for lower and upper age ranges. RESULTS: Nominal sized 2.5, 3, 3.5, 3.7, 4, 4.5, 5, and 6 rigid bronchoscopes were included. In five recommendations, the rigid bronchoscopes' OD was larger than the internal cricoid diameter in the upper age range, whereas in one recommendation the ratio (OD rigid bronchoscope to ID of cricoid) ranged between 77% and 90% for the upper age and between 95% and 109% for the lower age range. In only one of the six recommendations was the rigid bronchoscope OD larger than the tracheal ID. Ratios for the left and right proximal mainstem bronchus ranged from 70% to 146% for the upper and from 78% to 156% for the lower age range, with the highest ratios for the left proximal mainstem bronchus. CONCLUSION: Based on this in vitro study, most of the recommendations analyzed result in a balanced fit of rigid bronchoscopes within the cricoid. Since the left mainstem bronchus is considerably smaller than the cricoid, any insertion on this level will require careful endoscopic guidance to avoid damage to the left mainstem bronchus.

Dimensional compatibility and limitations of tracheal intubation through supraglottic airway devices: a mannequin-based in vitro study.

BACKGROUND: Flexible bronchoscope-guided tracheal intubation through supraglottic airway devices (SGAs) is a well-established element of difficult intubation algorithms. Success can be limited by dimensional incompatibilities between tracheal tubes (TTs) and SGAs. METHODS: In this in vitro study, we tested the feasibility of TT passage through SGAs, removal of SGAs over TTs, and the ability to guide the flexible bronchoscope with 13 TT brands (internal diameter, 6.5-8.0 mm) and ten different SGAs (#4 and #5) in an intubation mannequin. RESULTS: We tested 1,040 combinations of SGAs and TTs. Tracheal tube passage failed in 155 (30%) combinations of the five tested first-generation SGAs (117 [46%] with SGA #4, 38 [15%] with SGA #5) and in three (0.6%) combinations of the five tested second-generation SGAs (two [0.8%] with SGA #4 and one [0.4%] with SGA #5). The reason for failed passage of a TT through a first-generation SGA consistently was a too-narrow SGA connector. Removal of the SGA over the TT in the 882 remaining combinations was impossible for all sizes of reinforced TTs, except the Parker Reinforced TT, and was possible for all non-reinforced TTs. Only one combination with SGA #4 and 84 combinations with SGA #5 were not ideal to adequately guide the flexible bronchoscope. CONCLUSION: Clinically relevant combinations of adult-size TTs and SGAs can be incompatible, rendering flexible bronchoscope-guided tracheal intubation through an SGA impossible. Additional limitations exist regarding removal of the SGA and maneuverability of the flexible bronchoscope.

RéSUMé: CONTEXTE: L'intubation endotrachéale guidée par bronchoscope flexible via un dispositif supraglottique (DSG) est un élément établi des algorithmes utilisés pour les intubations difficiles. La réussite de l'intubation peut être limitée par des incompatibilités dimensionnelles entre les tubes endotrachéaux (TET) et les DSG. MéTHODE: Dans cette étude in vitro, nous avons testé la faisabilité de faire passer un TET par un DSG, le retrait du DSG par-dessus le TET et la possibilité de guider un bronchoscope flexible avec 13 marques de TET (diamètre interne, 6,5-8,0 mm) et dix DSG différents (#4 et #5) sur un mannequin d'intubation. RéSULTATS: Nous avons testé 1040 combinaisons de DSG et de TET. Le passage du tube endotrachéal a échoué dans 155 (30 %) combinaisons avec les cinq DSG de première génération testés (117 [46 %] avec DSG #4, 38 [15 %] avec DSG #5) et dans trois (0,6 %) combinaisons avec les cinq DSG de deuxième génération testés (deux [0,8 %] avec DSG #4 et une [0,4 %] avec DSG #5). La raison de l'échec du passage d'un TET à travers un DSG de première génération était systématiquement liée à un connecteur de DSG trop étroit. Dans les 882 combinaisons restantes, le retrait du DSG par-dessus le TET s'est avéré impossible avec toutes les tailles de TET armés, à l'exception du TET armé Parker, et était possible avec tous les TET non armés. Une seule combinaison avec le DSG #4 et 84 combinaisons avec le DSG #5 n'étaient pas idéales pour guider le bronchoscope flexible de manière adéquate. CONCLUSION: Les combinaisons cliniquement pertinentes de TET et de DSG de tailles adultes peuvent être incompatibles, rendant impossible l'intubation endotrachéale guidée par bronchoscope flexible via un DSG. D'autres limites existent en ce qui concerne le retrait du DSG et la maniabilité du bronchoscope flexible.

Flow irregularities from syringe infusion pumps caused by syringe stiction.

OBJECTIVE: The current study aimed to evaluate the extent of the slide-stick phenomenon in differently designed infusion syringes at various infusion rates and filling positions. METHODS: Fluid delivery from three 50-mL infusion syringe brands (BD; Codan; Fresenius) was investigated using a flow sensor at flow rates of 0.5, 1.0, or 5.0 mL h-1 , with the syringes filled with either 10, 30, or 50 mL of distilled water. Two identical models (A/B) of the same infusion pump model were used. The effect of flow rate variations on the plasma concentration of a continuous epinephrine infusion in a 3 kg neonate receiving a continuous infusion of 0.1 µg kg min-1 epinephrine was studied using a pharmacokinetic simulation model. RESULTS: Considerable variations in calculated plasma epinephrine concentration were detected between flow rates of 5 and 0.5 or 1 mL h-1 for all syringe types and filling volumes. The median deviation of plasma concentration for the 5 mL h-1 flow rate varied depending on assembly from 1.3% (Codan) to 1.8% (Fresenius). This was more pronounced for lower flow rates, where at 1 mL h-1 the deviation varied from 3.3% (BD) to 4.8% (Fresenius) and at 0.5 mL h-1 from 4.9% (BD) to 5.4% (Fresenius). Differences between filling volumes (within syringe type and flow rate) did not appear to have relevant influence on variations in calculated plasma epinephrine concentration. CONCLUSION: Infusion set rate rather than syringe brand or filling volume was a major predictor for syringe stiction-related amount of variation in the calculated plasma epinephrine concentration.

Spinal meningeal cyst in a child with Marfan syndrome: A potential cause for apparent dural puncture during caudal epidural block.

We report a complication from caudal epidural block for anesthesia in a 4-year-old child with Marfan syndrome who was undergoing lensectomy, orchidopexy, and circumcision resulting in apparent accidental dural puncture. Subsequent magnetic resonance imaging revealed a lumbosacral spinal meningeal cyst.

Frequency distribution of modified Cormack-Lehane views-A retrospective audit of tracheal intubation in children with normal airways.

BACKGROUND: Paediatric patients with an unanticipated poor grade of laryngoscopic view during tracheal intubation represent a challenging situation potentially associated with increased morbidity and mortality. The aim of this study was to investigate the frequency of modified Cormack-Lehane (MCL) views and to elucidate variables for poor views in a large collective of children without anticipated airway difficulties. METHODS: The departmental anaesthesia patient database was searched for patients who had undergone general anaesthesia with tracheal intubation between January 2007 and March 2017. Inclusion criteria were age from birth to 17.99 years, general anaesthesia with tracheal intubation using direct laryngoscopy, no history, symptoms or signs of a difficult airway and the best obtained MCL view documented in the database. Patient- and anaesthesia-related variables associated with a poor view (MCL IIb, III and IV) were elucidated using a logistic regression model. RESULTS: In all, 22 965 patients were included; of these, 17 593 were observed only once. The prevalence of the first observed MCL views I, IIa, IIb, III and IV was 90.6%, 8.5%, 0.86%, 0.05% and 0%, respectively. The logistic regression model indicates that age and gender are the most important variables associated with MCL views IIb and III in the model. The probability for MCL views IIb/III decreases across the first 5-7 years before increasing again. CONCLUSIONS: The incidence of a poor grade of laryngoscopic view was found to be very low in children with a normal airway. They mainly occurred in infants and adolescent patients and were more common in male patients.

Fevipiprant has a low risk of influencing co-medication pharmacokinetics: Impact on simvastatin and rosuvastatin in different SLCO1B1 genotypes.

Fevipiprant, a prostaglandin D2 receptor 2 antagonist, is in clinical development as a treatment for asthma. The goal of this study was to assess the potential of fevipiprant to cause drug-drug interactions (DDI) as a perpetrator, that is, by altering the pharmacokinetics (PK) of co-medications. In vitro drug interaction studies of clinically relevant drug metabolizing enzymes and transporters were conducted for fevipiprant and its acyl glucuronide (AG) metabolite. Comparison of Ki values with unbound systemic or portal vein steady-state plasma exposure of fevipiprant and its AG metabolite revealed the potential for inhibition of organic anion transporting polypeptide 1B1 (OATP1B1) transporters (R-value of 5.99), while other targets including cytochrome P450 enzymes were not, or only marginally, inhibited. Consequently, an open-label, two-part, two-period, single-sequence clinical study assessed the effect of fevipiprant 450 mg QD on the pharmacokinetics of simvastatin 20 mg and rosuvastatin 20 mg, two statins with different dependency in OATP1B1-mediated hepatic uptake, in healthy adult volunteers. The study also assessed the pharmacogenetics of the SLCO1B1 gene, which encodes OATP1B1. Clinically, fevipiprant 450 mg QD showed a low potential for interaction and increased the peak concentrations of simvastatin acid and rosuvastatin by 2.23- and 1.87-fold, respectively, with little or no impact on total exposure. Genotype analysis confirmed that SLCO1B1 genotype influences statin pharmacokinetics to a similar extent either with or without fevipiprant co-administration. In summary, fevipiprant at 450 mg QD has only minor liabilities as a perpetrator for DDI.

Pediatric airway dimensions-A summary and presentation of existing data.

BACKGROUND: Age-related pediatric airway dimension reference values for cricoid, tracheal, and bronchial diameters as well as tracheal and bronchial lengths are essential for distinguishing normal from pathological airway findings and for manufacturing and selecting appropriately sized airway equipment. AIM: The aim of this work was to summarize and present existing pediatric airway dimension data for the larynx, trachea, and main stem bronchi from fetus to adolescence. METHODS: A systematic literature search was carried out using PubMed, Scopus, Embase, and Google Scholar. Publications containing original data on pediatric airway dimensions as mean or median in tabular form and spanning narrow age groups of 1 or 2 years were included in our study. Original data such as diameters, lengths, and cross-sectional areas of trachea, cricoid, left and right main bronchi in fetuses and children were collected and presented as figures. RESULTS: Pediatric airway dimension data were gathered and compiled from 15 studies fulfilling the inclusion criteria. Data were obtained from different measurement methods such as autopsy, chest X-ray, computed tomography, magnetic resonance imaging, rigid and flexible bronchoscopy as well as ultrasound examinations. There was considerable variation among age-related data due to biologic heterogeneity, different presentation of data, different definitions, and various measurement techniques. CONCLUSION: This investigation revealed heterogeneous data on pediatric airway dimensions, making it impossible to compile them into standard reference values for airway dimensions. New studies with structured and standardized measurements and data presentation in large populations of children are required to provide more valid pediatric airway dimension data.

Factors associated with intravenous lidocaine in pediatric patients undergoing laparoscopic appendectomy - a retrospective, single-centre experience.

BACKGROUND: Due to its potential beneficial effects, intra- and postoperative application of intravenous lidocaine has become increasingly accepted over the last couple of years, e.g. in patients undergoing laparoscopic surgical procedures. Based on its beneficial properties, lidocaine was introduced to the standard of care for all pediatric laparoscopic procedures in our institution in mid-2016. In contrast to adult care, scarce data is available regarding the use of perioperative intravenous lidocaine administration in children undergoing laparoscopic procedures, such as an appendectomy. METHODS: Retrospective analysis of all pediatric patients undergoing laparoscopic appendectomy at the University Children's Hospital Zurich in 2016. Perioperative data, as recorded in the electronic patient data management system, were evaluated for any signs of systemic lidocaine toxicity (neurological and cardiovascular), behavioral deterioration, as well as for hemodynamic instability. Additionally, the incidence of postoperative nausea and vomiting, administration of pain rescue medication, time to hospital discharge and to first bowel movement, as well as any postoperative complications were recorded. Starting on 01/07/2016, all patients undergoing laparoscopic surgery received intravenous lidocaine (1.5 mg/kg body weight (BW) bolus after induction of anesthesia followed by continuous infusion of 1.5 mg/kgBW/h). These patients were then compared to children without lidocaine administration who had undergone laparoscopic appendectomy between 01/01/2016 and 30/06/2016. RESULTS: Data of 116 patients was analyzed. Of these, 60 patients received lidocaine. No signs of systemic toxicity, neurologic impairment or circulatory disturbances were noted in any of these patients. A (non-significant) difference in the incidence of emergence delirium was observed (0 cases in the lidocaine group vs. 4 cases in the control group, p = 0.05). CONCLUSION: This retrospective analysis did not reveal any adverse effects in pediatric patients receiving intravenous lidocaine for laparoscopic appendectomy under general anesthesia. However, further trials investigating beneficial effects as well as pharmacokinetic properties of intravenous lidocaine in children are required.

Airway dimensions from fetal life to adolescence-A literature overview.

BACKGROUND: Data on airway dimensions in pediatric patients are important for proper selection of pediatric airway equipment such as endotracheal tubes, double-lumen tubes, bronchial blockers, or stents. The aim of the present work was to provide a synopsis of the available data on pediatric airway dimensions. METHODS: A systematic literature search was carried out in the PubMed database, Scopus, Embase, Web of Science, Prisma, and Google Scholar and secondarily completed by a reference search. Based on inclusion and exclusion criteria, a final selection of 109 studies with data on pediatric airway dimensions published from 1923 to 2018 were further analyzed. RESULTS: Six different airway measurement methods were identified. They included anatomical examinations, chest X-ray, computed tomography, magnetic resonance tomography, bronchoscopy, and ultrasound. Anatomical studies were more abundant compared to other methods. Data provided were very heterogeneously presented and powered. In addition, due to different study conditions, they are hardly comparable. Among all, anatomical and computer tomography studies are thought to provide the most reliable data. Ultrasound is an upcoming technique to estimate airway parameters of fetus and premature infants. There was, in general, a lack of comprehensive studies providing a complete range of airway dimensions in larger groups of patients from birth to adolescence. CONCLUSIONS: This work revealed a large heterogeneity of studies providing data on pediatric airway dimensions, making it impossible to compare, or assemble them to normograms for clinical use. Comprehensive studies in large population of children are needed to provide full range nomograms on pediatric airway dimensions.

Perioperative intravenous fluid therapy in children: guidelines from the Association of the Scientific Medical Societies in Germany.

This consensus- based S1 Guideline for perioperative infusion therapy in children is focused on safety and efficacy. The objective is to maintain or re-establish the child's normal physiological state (normovolemia, normal tissue perfusion, normal metabolic function, normal acid- base- electrolyte status). Therefore, the perioperative fasting times should be as short as possible to prevent patient discomfort, dehydration, and ketoacidosis. A physiologically composed balanced isotonic electrolyte solution (BS) with 1-2.5% glucose is recommended for the intraoperative background infusion to maintain normal glucose concentrations and to avoid hyponatremia, hyperchloremia, and lipolysis. Additional BS without glucose can be used in patients with circulatory instability until the desired effect is achieved. The additional use of colloids (albumin, gelatin, hydroxyethyl starch) is recommended to recover normovolemia and to avoid fluid overload when crystalloids alone are not sufficient and blood products are not indicated. Monitoring should be extended in cases with major surgery, and autotransfusion maneuvers should be performed to assess fluid responsiveness.

Task-related fMRI responses to a nicotinic acetylcholine receptor partial agonist in schizophrenia: A randomized trial.

INTRODUCTION: AQW051, an α7-nicotinic acetylcholine receptor partial agonist, enhanced cognitive function in rodent models of learning and memory. This study evaluated brain activation during performance of a working memory task (WMT) and an episodic memory task (EMT), and the effect of AQW051 on task-related brain activation and performance in subjects with schizophrenia. METHODS: This was a double-blind, randomized, placebo-controlled, multicenter, 2-period cross-over trial (NCT00825539) in participants with chronic, stable schizophrenia. Participants, stratified according to smoking status, were randomized (1:1:1:1:1:1) to 1 of 6 sequence groups that determined the study drug dose (AQW051 7.5mg, 50mg or 100mg) and order of administration versus placebo. The primary outcome was brain activation in a priori target regions of interest (ROIs) during performance of the WMT and EMT, measured using functional magnetic resonance imaging. The effect of AQW051 on task-related (EMT and WMT) brain activation and performance was also assessed, as were safety and tolerability. RESULTS: Overall, 60 of 68 enrolled participants completed the study (AQW051 then placebo: 7.5mg n=9; 50mg n=11; 100mg n=10. Placebo then AQW051: 7.5mg n=10; 50mg n=11; 100mg n=9). Significant task-related brain activation (5% significance level) was observed with placebo. During the WMT, a medium effect size was observed in the inferior prefrontal cortex with AQW051 100mg versus placebo (0.431; p=0.105). During the EMT encoding phase, a large effect size was observed in the anterior hippocampus (0.795; p=0.007) and a medium effect size in the posterior hippocampus (0.476; p=0.079) with AQW051 7.5mg. No other medium/large effect sizes were observed with any dose on either task. Effects on brain activation were generally not associated with changes in cognitive performance. AQW051 was well tolerated with an acceptable safety profile. CONCLUSIONS: Overall, no consistent effects of AQW051 on brain regions involved in the performance of a WMT or EMT were observed; however, this study presents a model for evaluating potential response to pharmacological interventions for cognitive impairment in schizophrenia.

The oral CRTh2 antagonist QAW039 (fevipiprant): A phase II study in uncontrolled allergic asthma.

BACKGROUND: There is an unmet medical need for allergic asthma patients who are uncontrolled on conventional therapies. The aim of this study was to collect efficacy and safety data for QAW039, an oral chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2) receptor antagonist, for the treatment of asthma. METHODS: This was an exploratory phase II, double-blind, randomized, placebo-controlled multi-center study. Patients with mild-to-moderate uncontrolled allergic asthma (N = 170) were either without or weaned off inhaled corticosteroids (ICS) and long-acting ß-agonists (LABA) and randomized (1:1) to QAW039 (500 mg once daily) or to placebo for 28 days. RESULTS: Overall, 157 patients completed the study. There were no significant differences between QAW039 and placebo for trough forced expiratory volume in 1 s (FEV1) or Asthma control questionnaire (ACQ) in the total population. Subgroup analyses demonstrated that patients with a FEV1 <70% of predicted at baseline treated with QAW039 had significant improvement compared with placebo in trough FEV1 (QAW039- Placebo [Δ] = 207 mL; 90% confidence interval [CI]: 96, 319; P = 0.002) and ACQ7 (Δ = -0.41; 90%CI: -0.69, -0.13; P = 0.009). QAW039 reached a mean maximum concentration (Cmax) of 3440 ng/mL on day 28 at a median Tmax of 1 h (range 0.5-4 h). Most adverse events (AEs) were mild/moderate and balanced between both groups, with no serious AEs. CONCLUSIONS: In the general study population, no improvement in lung function was observed with QAW039. However, a subgroup analysis revealed that patients with greater severity of airflow limitation (FEV1 < 70%) had improved lung function and asthma control when treated with QAW039. QAW039 also demonstrated a favorable safety profile. TRIALS REGISTRATION: ClinicalTrials.govNCT01253603.

Evaluation of the minimum volume of salvage blood required for the successful use of two different autotransfusion devices.

BACKGROUND: Autotransfusion in pediatric anesthesia is beneficial in several clinical settings; however, more frequent usage is deterred by process-related costs and the fact that the absolute volume of blood returned may be minimal. OBJECTIVE: Two autotransfusion devices (CATS, Fresenius Kabi AG, and Sorin Xtra, Sorin GmbH) with different technologies were evaluated to determine the minimum volume necessary to efficiently process salvage blood. METHODS: Banked blood was diluted to simulate different clinical scenarios. Volume and red cell mass in returned blood were analyzed as a function of initial volume and red cell mass in the collection reservoir using incremental increases in the volume of blood added to the reservoir. RESULTS: The volume of the returned processed blood for infusion was dependent on degree of dilution and blood volume in the reservoir. The CATS required a smaller initial minimum volume to process and successfully return; however, the Xtra provided a more efficient recovery at low initial collected volumes. Using test blood of various degrees of dilution, the CATS and Xtra were able to return blood for retransfusion after a mean initial red cell mass of 48.7 ml (±4.9 ml) and 53.7 ml (±5.0 ml) were processed, respectively. CONCLUSIONS: Red cell mass rather than salvaged blood volume represents a reliable predictor of the successful use of an autotransfusion device. Measuring the hematocrit of the salvaged blood could improve the use of the devices. The investigated devices are likely to be roughly equivalent in effectiveness.