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Intrauterine growth restriction affects up to 10% of all pregnancies, leading to fetal programming with detrimental consequences for lifelong health. However, no therapeutic strategies have so far been effective to ameliorate these consequences. Our previous study has demonstrated that a single dose of nutrients administered into the amniotic cavity, bypassing the often dysfunctional placenta via intra-amniotic administration, improved survival at birth but not birthweight in an intrauterine growth restriction rabbit model. The aim of this study was to further develop an effective strategy for intra-amniotic fetal therapy in an animal model. Intrauterine growth restriction was induced by selective ligation of uteroplacental vessels on one uterine horn of pregnant rabbits at gestational day 25, and fetuses were delivered by cesarean section on GD30. During the five days of intrauterine growth restriction development, three different methods of intra-amniotic administration were used: continuous intra-amniotic infusion by osmotic pump, multiple intra-amniotic injections, and single fetal intraperitoneal injection. Technical feasibility, capability to systematically reach the fetus, and survival and birthweight of the derived offspring were evaluated for each technique. Continuous intra-amniotic infusion by osmotic pump was not feasible owing to the high occurrence of catheter displacement and amnion rupture, while methods using two intra-amniotic injections and one fetal intraperitoneal injection were technically feasible but compromised fetal survival. Taking into account all the numerous factors affecting intra-amniotic fetal therapy in the intrauterine growth restriction rabbit model, we conclude that an optimal therapeutic strategy with low technical failure and positive fetal impact on both survival and birthweight still needs to be found.

Objectives Haemolysis caused by the use of peristaltic infusion pumps (PIPs) has been described in human and canine packed red blood cells (pRBCs). The aim of this study was to evaluate the effects of two different linear PIPs on the haemolysis of feline pRBC units stored for a long time. Methods Feline pRBC units stored with adenine, dextrose, mannitol and sodium chloride (SAGM) were manufactured. After 35–42 days of storage at 2–4°C, a line administration system with a 180 µm filter was attached to every pRBC bag, the system was drained by gravity alone (8 drops/min) and a 1.3 ml sample was collected (G). A NIKI V4 pump was then used at a flow rate of 25 ml/h, the flow was stopped when the infusion system was filled with blood coming from the infusion pump and another 1.3 ml sample was collected (NK). Finally, an Infusomat FmS pump was evaluated, collecting another 1.3 ml sample (IM). Packed cell volume (PCV) was measured in all samples by microhaematocrit centrifugation, total haemoglobin (HGB) was measured using a specific haemoglobin analyser and, after centrifugation, free HGB was determined by spectrophotometry. The percentage of haemolysis was calculated. Friedman’s test was used to compare the samples. Results Fifteen feline pRBC units were evaluated. The average degree of haemolysis for sample G (gravity-assisted) was 1.12%. Comparison of the degree of gravity-assisted haemolysis with haemolysis in PIP NK (1.13%) and IM (1.14%) samples revealed no significant differences, with differences of only 0.01% and 0.02%, respectively. Conclusions and relevance The results of this study demonstrate that the use of two common PIPs in veterinary hospitals does not produce levels of haemolysis that are significantly different than that caused by gravity alone during transfusion of feline pRBCs at a rate of 25 ml/h.

For effective patient therapy and improved patient safety, it is critical to administer medication accurately in accordance with doctor’s prescription. However, accidents owing to the erroneous programing of infusion pumps caused by users have been consistently reported in several documents. In this study, the authors propose a novel surveillance technique for infusion pumps to continuously monitor the variations in panel digits using a convolutional neural network model, and evaluate the performance of the implemented technique. During the experimental evaluation, 1st-step ROIs and 2nd-step ROIs were successfully extracted from the frame images regardless of the ambient lighting conditions. The final accuracies of the implemented CNN model are 99.9% for both the training (172,800 images) and validation (1080 images) dataset while the final losses for the training and validation datasets are 0.48 and 0.45 after 13th epoch, respectively. In the 24-h continuous monitoring test, the accuracy of the model for volume recognition considering all the 1440 measurements (960 for day-lighting and 480 for night-lighting) is 95.5%, whereas in day-lighting and night-lighting modes the accuracies of the model are 98.2% and 90.0%, respectively. Based on these experimental results, the proposed surveillance technique incorporating infusion pumps is expected to improve the safety of patients who need long-term treatments via infusion pumps, reducing the burden on the nurses and hospitals.

Background Elderly patients with rib fractures carry a high morbidity rate, particularly due to pulmonary complications as decreased respiratory efforts ensue secondary to pain. Risk of bleeds in the elderly on anticoagulant therapy is high. The effort to reduce narcotic use in patients is now a health care priority. We propose that the use of paravertebral analgesia (PVA) pumps is an alternative pain control method with less risk and easy placement. Methods Two hundred and seventy-nine patients were admitted with multiple fractured ribs to the Trauma Center of Community Hospital and treated with the application of continuous PVA via a pump (72 patients). Pain scores were recorded before and after the initiation of the pump. These patients were compared with a group of the remaining 207 patients who received intravenous narcotics only. Results The mean change from baseline in pain scores for all patients was 1.43 (SD = 2.75). The mean change in pain for the treatment group was 1.93 (SD = 2.60), and the change in pain for the control group was 1.24 (SD = 2.79). Change in pain differed between groups (1.3 vs 1.8; P = .01) although it was a small difference. After adjusting for age, gender, Injury Severity Score, Glasgow Coma Scale, number of fractures, and comorbid conditions, there was no significant difference in pain post-procedure (odds ratio = 0.75; P = 0.39) with an effect size of 30% and total sample size of 279. Conclusion The PVA pump using bupivacaine is an effective safe and alternative method for managing elderly patients with rib fractures eliminating the serious side effects associated with narcotics.

Background: Studies evaluating the risk of developing acute kidney injury (AKI) with different dosing strategies of polymyxin B are limited. Objectives: To compare the incidence of AKI in patients treated with intermittent versus continuous polymyxin B therapy. Secondary objectives included time to onset of AKI, hospital length of stay (LOS), and all-cause hospital mortality. Variables associated with an increased risk of AKI were evaluated. Methods: A retrospective record review was conducted at a single center in Puerto Rico. Adult patients (≥18 years old) treated with polymyxin B (first course) for at least 48 hours from 2013-2015 were evaluated. Patients with a creatinine clearance 25 kg/m2 on polymyxin B via continuous infusion had a significantly higher cumulative incidence of AKI ( P = 0.016). Conclusion and Relevance: No difference in the risk of polymyxin B nephrotoxicity was found between intermittent and continuous infusion administration. Administration of polymyxin B via a continuous infusion may result in a higher risk of AKI in patients with a BMI >25 kg/m2.

Accuracy of insulin pump basal rate delivery, if tested according to the standard IEC 60601-2-24 for infusion pumps, shall be presented as a trumpet curve. This way of graphical presentation is common; however, it is often misunderstood and misinterpreted by people. It is often assumed that a trumpet curve shows the error rate as a function of time, thus implying an increasing accuracy in the course of time. On the contrary, the horizontal axis of a trumpet curve shows increasingly long observation windows. In addition, trumpet curves display only extreme values, that is, those windows with minimal and maximal deviation, which might not be representative for the total deviation. This commentary provides information regarding the calculations and the interpretation of trumpet curves and proposes alternative approaches.

Background The EPOCH regimen, consisting of vincristine sulfate, doxorubicin hydrochloride, and etoposide phosphate, is typically administered by continuous infusion over four days to oncology inpatients. If the EPOCH regimen was available to be administered through portable elastomeric pumps, chemotherapy could be transitioned to an outpatient setting, reducing inpatient bed days and overall healthcare costs. However, a lack of stability data for the admixtures in the elastomeric infusion devices currently prevents the transition of the regime to an outpatient setting. The purpose of this study is to determine the physical and chemical stability of the admixture in polyisoprene elastomeric pumps under different storage conditions to support the transition of the EPOCH regime to an outpatient setting. Methods The physico-chemical stability of three admixtures at a range of clinically relevant concentrations compounded in polyisoprene elastomeric infusors was determined when refrigerated at 2–6℃ over a 14-day period followed by 35℃ up to 7 days in the dark, and under standardized fluorescent light to simulate scenarios in clinical practice. Results All tested admixtures were compatible and the drugs were stable in the elastomeric infusors for up to 14 days when stored at 2–6℃ followed by 7 days at 35℃ in the dark, with nominal losses of Conclusion The extended stability of the three infusional admixtures compounded in elastomeric infusion pumps demonstrated herein permits advance preparation and storage of these drugs, reducing pharmacy compounding resources. The demonstrated stability at 35℃ and under light exposure, conditions more severe than those experienced during clinical practice, support continuous infusions for up to seven days from the elastomeric infusors without a loss of potency. The proven stability of the EPOCH regimens in the tested elastomeric infusion device supports the transition of treatment to an outpatient setting which will reduce inpatient bed days and overall healthcare costs.

Peristaltic pumps rely on constant compression of elastomeric tubing from which particles may be shed, a phenomenon known as spallation. We studied spallated particles on microfluidic filtration devices with photolithographically prepared micron-level pore fields. Filtration of ultra-pure water through these pores was analyzed using either the usual peristaltic pump or a reciprocating pair of syringe pumps. Using syringe pumps, transmembrane pressure (TMP) values during filtration at 2.5 cm3/min revealed steady filtration for over 80 minutes at 2.3 mmHg. Using the peristaltic pump, TMP was never stable, increasing to approximately 11 mmHg during the first 10 minutes. Pore plugging was the culprit, evidenced by post-perfusion microphotography.

Background: Limited published data exists quantifying the influence of human factors (HF) and pen needle (PN) design on delivery outcomes of pen injection systems. This preclinical in vivo study examines the impact of PN hub design and applied force against the skin during injection on needle penetration depth (NPD). Method: To precisely locate injection depth, PN injections (20 µl; 2 IU, U-100 volume equivalent) of iodinated contrast agent were administered to the flank of Yorkshire swine across a range of clinically relevant application forces against the skin (0.25, 0.75, 1.25, and 2.0 lbf). The NPD, representing in vivo needle tip depth in SC tissue, from four 32 G × 4 mm PN devices (BD Nano™ 2nd Gen and three commercial posted-hub PN devices; n = 75/device/force, 1200 total) was measured by fluoroscopic imaging of the resulting depot. Results: The reengineered hub design more closely achieved the 4 mm target NPD with significantly less variability ( P = .006) than commercial posted-hub PN devices across the range of applied injection forces. Calculations of IM (intramuscular) injection risk completed through in silico probability model, using NPD and average human tissue thickness measurements, displayed a commensurate reduction (~2-8x) compared to conventional PN hub designs. Conclusions: Quantifiable differences in injection depth were observed between identical labeled length PN devices indicating that hub design features, coupled with aspects of variable injection technique, may influence injection depth accuracy and consistency. The reengineered hub design may reduce the impact of unintended individual technique differences by improving target injection depth consistency and reducing IM injection potential.

Purpose Elastomeric pumps are used to administer 46-hour infusions of 5-fluorouracil (5FU). Baxter suggests patients visually monitor their pumps to ensure that infusions are proceeding correctly. This can be confusing and lead to concerns about under- or over-dosing. Baxter has not considered weighing pumps as a validated method for monitoring. This study aims to validate weighing as a more accurate method for patients and healthcare professionals, and describe real life Baxter Infusor™ variability. Methods Patients who had been started on a 46-hour 5FU infusion returned to the clinic approximately 24 h after starting treatment. The pump was weighed on a StarFrit kitchen scale, and date, time, and weights recorded. Patients were asked if they had a preference for weighing or visually inspecting their pump. Results Pumps ( n = 103) were weighed between 17.25 and 27.5 h after connection. The average weight of a pump was 189 g. Of 103 pumps weighed, 99 weighed less than expected, corresponding to average flow rates of 5.69 mL/h over the elapsed time. The expected flow rate is 5 mL/h with 10% variability. Average flow rates within the 17.25- to 27.5-hour window were 4.561 mL/h, which is 8.78% slower than expected, but within the 10% known variability. Forty-seven percent of patients didn’t have a preference for either method, but for those who did have a preference, more than twice as many preferred weighing. Conclusion With proper education, weighing Baxter Infusors at home with kitchen scales can be an accepted and objective alternative to the current recommendation of visual inspection.

The delivery of most therapeutic agents is rendered ineffective for the treatment of brain diseases due to the presence of the blood–brain barrier (BBB). The goal of this study was to investigate the effect of pre-infusion focused ultrasound (FUS) and microbubbles on the distribution of direct brain infusion in vivo. A single-element FUS transducer was used in all sonications, which were carried out immediately prior to direct infusion procedures. Mice received direct infusion of either Gadolinium-labeled albumin (Gd-albumin, 74 kDa) or adeno-associated virus (AAV, ∼4 MDa). The volumes of Gd-albumin at 30 min were deemed comparable ( P = 0.334) between the direct infusion (DI)-only group and the FUS + DI group. At 120 min, the FUS + DI group showed significantly higher contrast-enhanced volume (9.76 ± 0.74 mm3) than the DI-only group (7.14 ± 0.34 mm3). For mice infused with AAV, the total volume of transduction was estimated as GFP-positive regions and FUS + DI group demonstrated significantly higher ( P = 0.017) transduction efficiency in vivo. In conclusion, enhanced bio-distribution of directly infused agents was observed when the targeted region was pre-conditioned with FUS and microbubbles. Focused ultrasound has the potential, as an adjuvant technique, to significantly enhance direct brain infusion and achieve the desired therapeutic outcomes.

Background: Home health services in the United States(US) have been on a rise. Hospice patients cope with diverse physical and pain symptoms; medical devices are used for symptom management to improve their quality-of-care at end-of-life. Objective: Using the National Home and Hospice Care Survey (NHHCS), the study summarizes medical device use for symptom management and tracks various demographic variables for home hospice patients. Methods: A cross-sectional analysis of data using the 2007 NHHCS was conducted. There were 4733 hospice discharges which corresponded to 2,505,011 individuals in US with sampling weights. The data was analyzed using chi square tests and confounding factors adjusted with logistic regression. Results: Eighty-nine percent of hospice discharges were evaluated for pain at first assessment. The regression model for pain at first assessment was significantly associated with use of patient controlled analgesia (OR = 1.82, 95% CI = 1.28, 2.59) and urinary catheters (OR = 1.16, 95% CI = 1.02, 1.33). Patient with dyspnea were associated with significant use of oxygen (OR = 3.00, 95% CI = 2.64, 3.40) and metered dose inhaler (OR = 2.43, 95% CI = 1.92, 3.07). There was negligible use of total parenteral nutrition (TPN) noted in the study. Conclusion: In conclusion, the study highlights medical device use in home hospice care for end-of-life symptom management. It noted the significant use of IV infusion pumps and patient controlled analgesia. Conversely, there is little use of TPN or CPAP in patients with anorexia or dyspnea. While missing data on critical symptom evaluations regrettably raises questions about the validity of the study, the NHHCS serves as an important reservoir of data on the growing population of home hospice patients.

Purpose Elastomeric pumps are used to infuse a 46-h fluorouracil protocol and patients are asked to visually inspect the pump daily. The pump has a variability of ±10% and there are additional patient variables that can increase this. The feasibility of weighing the pump rather than a visual inspection along with the secondary objective to confirm the pump’s variability in real world conditions was undertaken. Methods Empty pumps were weighed using both pharmacy and kitchen scales. Pumps upon completion of the 46-h infusion were also weighed using both pharmacy and kitchen scales. Results The kitchen scale was as accurate as the pharmacy grade scale. Disconnected pumps showed the expected variability from using these infusor pumps along with a few showing greater variability likely due to patient variables. Conclusion Weighing pumps appears to be feasible both at the pharmacy and home level. Next steps would be to weigh pumps during the infusion to validate an alternate method to simple visual inspection for patients to confirm proper infusing of the pump at their home.

Background: Commercial glucagon is unstable due to aggregation and degradation. In closed-loop studies, it must be reconstituted frequently. For use in a portable pump for 3 days, a more stable preparation is required. At alkaline pH, curcumin inhibited glucagon aggregation. However, curcumin is not sufficiently stable for long-term use. Here, we evaluated ferulic acid, a stable breakdown product of curcumin, for its ability to stabilize glucagon. Methods: Ferulic acid-formulated glucagon (FAFG), composed of ferulic acid, glucagon, L-methionine, polysorbate-80, and human serum albumin in glycine buffer at pH 9, was aged for 7 days at 37°C. Glucagon aggregation was assessed by transmission electron microscopy (TEM) and degradation by high-performance liquid chromatography (HPLC). A cell-based protein kinase A (PKA) assay was used to assess in vitro bioactivity. Pharmacodynamics (PD) of unaged FAFG, 7-day aged FAFG, and unaged synthetic glucagon was determined in octreotide-treated swine. Results: No fibrils were observed in TEM images of fresh or aged FAFG. Aged FAFG was 94% intact based on HPLC analysis and there was no loss of bioactivity. In the PD swine analysis, the rise over baseline of glucose with unaged FAFG, aged FAFG, and synthetic native glucagon (unmodified human sequence) was similar. Conclusions: After 7 days of aging at 37°C, an alkaline ferulic acid formulation of glucagon exhibited significantly less aggregation and degradation than that seen with native glucagon and was bioactive in vitro and in vivo. Thus, this formulation may be stable for 3-7 days in a portable pump for bihormonal closed-loop treatment of T1D.

Background Drug leakage and lack of a drug-removal system have prevented clinical application of isolated pelvic perfusion (IPP). These barriers were overcome with negative-balance IPP (NIPP) in experimental pig models. Here, a phase 1 clinical study of NIPP was performed in patients with incurable symptomatic rectal cancer. Purpose To establish a safe regimen of high-dose regional chemotherapy with NIPP using cisplatin in patients with incurable rectal cancer. Material and Methods Between June 2004 and January 2007, NIPP therapy was performed for 23 patients (11 women, 12 men; mean age, 58 years). NIPP was routinely performed twice over a 4-week interval. Dose-limiting toxicities (DLTs) were defined using a 5 + 3 design, and cisplatin doses were escalated from 170 mg/m2, with a fixed 5-fluorouracil dose of 1000 mg/m2. The grade of adverse events (AEs) at the first and second sessions of NIPP therapy, pharmacokinetics, and antitumor response were evaluated. Results No DLTs were observed during the first session of NIPP. However, at the second session, two patients experienced the DLT of neuropathy after administration of 200 mg/m2 cisplatin. Therefore, 190 mg/m2 cisplatin was indicated as the maximum tolerated dose (MTD). The plasma pelvic-to-systemic exposure ratio was 18.4 based on the maximum concentration and 19.0 based on the concentration-time curve. Solid tumor responses included complete response in two patients, partial response in five patients, stable disease in 15 patients, and progressive disease in one patient. Conclusion NIPP may offer the safe delivery of high-dose regional chemotherapy (MTD of 190 mg/m2 cisplatin) with negligible AEs and effective control of tumor growth in patients with incurable rectal cancer.

Aim: The aim of this study was to examine the hydrodynamic performance and gaseous microemboli (GME) activity of two centrifugal pumps for possible use in low-flow extracorporeal CO2 removal. Materials & Methods: The performance of a Rotassist 2.8 and a Rotaflow 32 centrifugal pump (Maquet Cardiopulmonary AG, Hirrlingen, Germany) was evaluated in a water-glycerine mixture-filled in vitro circuit that enabled measurement of pressures and GME at the pump inlet and pump outlet. Pressure-flow curves were acquired in a 1,000 to 5,000 rpm range while increasing drainage resistance in one series and outlet resistance in another. Results: Respective minimum pump inlet and maximum pump outlet pressures were −539 mmHg and 754 mmHg for the Rotassist 2.8 and −606 mmHg and 806 mmHg for the Rotaflow 32. Maximum standard deviations on pump pressures and flow amounted to 3.0 mmHg and 0.03 L/min, respectively, regardless of pump type and drainage or outlet resistance. The GME at the pump outlet were detectable at pump inlet pressures below −156 mmHg at 0.2 L/min and 2,500 rpm for the Rotassist 2.8 and below −224 mmHg at 0.9 L/min and 3,000 rpm for the Rotaflow 32. Conclusion: Both the Rotassist 2.8 and Rotaflow 32 centrifugal pumps show a comparably high hydrodynamic stability, but potential GME formation with decreasing pump inlet pressures should be taken into account to ensure safe centrifugal pump-based low-flow extracorporeal CO2 removal.

Patient safety is a matter of major concern that involves every health professional. Nowadays, emerging technologies such as smart pumps can diminish medication errors as well as standardise and improve clinical practice with the subsequent benefits for patients. The aim of this paper was to describe the smart pump implementation process in a paediatric intensive care unit (PICU) and to present the most relevant infusion-related programming errors that were prevented. This was a comparative study between CareFusion Alaris Guardrails® and Hospira MedNet® systems, as well as a prospective and intervention study with analytical components carried out in the PICU of Gregorio Marañón General and Teaching Hospital. All intravenous infusions programmed with a pump in the eleven beds of the unit were analyzed. A drug library was developed and subsequently loaded into CareFusion and Hospira pumps that were used during a three month period each. The most suitable system for implementation was selected according to their differences in features and users’ acceptance. Data stored in the pumps were analyzed to assess user compliance with the technology, health care setting and type of errors intercepted. The implementation process was carried out with CareFusion systems. Compliance with the technology was 92% and user acceptance was high. Vacation substitution and drug administration periods were significantly associated with a greater number of infusion-related programming errors. High risk drugs were involved in 48% of intercepted errors. Based on these results we can conclude that implementation of smart pumps proved effective in intercepting infusion-related programming errors from reaching patients. User awareness of the importance of programming infusions with the drug library is the key to succeed in the implementation process.

Angiotensin-converting enzyme 2 (ACE2) is present in the heart and thought to exert protective functions. We conducted studies in ACE2 deficient mice to determine whether enzyme loss would exacerbate the cardiac and vascular pathological responses to chronic subcutaneous (sc) angiotensin II (Ang II) infusion. Eight-week-old male ACE2 knockout (KO) and wild type (WT) mice were infused with Ang II (1000 ng/kg per min, 4 weeks) using mini-osmotic pumps. Blood pressure (radiotelemetry), cardiac function (echocardiography, echo), cardiac/aortic structure (histology, collagen, and oxidative stress), and vascular inflammation were examined. Before Ang II infusion, ACE2 KO mice showed unaltered cardiac function and blood pressure. After 4 weeks of Ang II infusion, the mean arterial pressure (MAP) increased from 96 ± 2 to 136 ± 17 mm Hg (∼40%) in WT and from 104 ± 5 to 141 ± 13 mm Hg (∼ 35%) in ACE2 KO. While there were no differences in MAP between groups, the ACE2 KO responded differently to the hypertensive stimulus. Echo analysis revealed severe myocardial dysfunction in Ang II-infused ACE2 KO (Ang ACE2 KO). Ejection fraction was lower (39% versus 50%) as was fractional shortening (27% versus 38%) in ACE2 KO versus WT, respectively. Cardiac dysfunction was associated with hypertrophic cardiomyopathy shown by increased left-ventricular wall thickness, average cardiomyocyte cross-sectional area, and heart weight/body weight ratio. Collagen staining in the myocardium and aorta revealed increased collagen in Ang ACE2 KO, suggestive of remodeling. Results also showed enhanced oxidative stress in the myocardium and aorta of Ang ACE2 KO. There was a 3-fold elevation in macrophage inflammatory protein 1α (MIP 1α) in the aorta of ACE2 KO. Studies in the ACE2 KO model reveal the importance of ACE2 in the maladaptive cardiac and aortic responses to Ang II stimulation, seen as enhanced remodeling using physiological, structural, and biochemical markers. Results document a cardio- and vascular-protective role of ACE2 under pathological conditions.

We have developed a feedback-controlled bolus plus infusion (FC-B/I) method for monitoring the interaction between positron emission tomography (PET) ligands and their specific target molecules with PET. The usefulness of the FC-B/I method was evaluated by the direct interaction between [11C]raclopride, a dopamine D2 receptor (D2R) ligand, and cold raclopride (10 and 100 μg/kg) in the brains of conscious monkeys. The present results demonstrated that the FC-B/I method could achieve the equilibrium state of [11C]raclopride in the striatum of monkey brain, and also that the cold raclopride-induced reduction of [11C]raclopride binding to D2R was observed in a dose-dependent manner. Good correlations of distribution volume ratio of the striatum to cerebellum between the conventional bolus plus infusion (B/I) method and the FC-B/I method as well as between the conventional bolus injection method and the FC-B/I method were observed. These results indicated that the system could be a useful tool for the evaluation of interaction between drug candidates and their target molecules like enzymes, receptors, and transporters by using of their specific PET ligands.

Hypothermic machine perfusion (HMP) is regarded as a better preservation method for donor livers than cold storage. During HMP, livers are perfused through the inlet blood vessels, namely the hepatic artery (HA) and the portal vein (PV). In previous HMP feasibility studies of porcine and human livers, we observed that the PV flow decreased while the HA flow increased. This flow competition restored either spontaneously or by lowering the HA pressure (PHA). Since this phenomenon had never been observed before and because it affects the HMP stability, it is essential to gain more insight into the determinants of flow competition. To this end, we investigated the influence of the HMP boundary conditions on liver flows during controlled experiments. This paper presents the flow effects induced by increasing PHA and by obstructing the outlet blood vessel, which is the vena cava inferior (VCI). Flow competition was evoked by increasing PHA to 55-70 mmHg, as well as by obstructing the VCI. Remarkably, a severe obstruction resulted in a repetitive and alternating tradeoff between the HA and PV flows. These phenomena could be related to intra-sinusoidal pressure alterations. Consequently, a higher PHA is most likely transmitted to the sinusoidal level. This increased sinusoidal pressure reduces the pressure drop between the PV and the sinusoids, leading to a decreased PV perfusion. Flow competition has not been encountered or evoked under physiological conditions and should be taken into account for the design of liver HMP protocols. Nevertheless, more research is necessary to determine the optimal parameters for stable HMP. ispartof: International Journal of Artificial Organs vol:35 issue:2 pages:119-131 ispartof: location:United States status: published

Purpose To compare, under controlled conditions similar to practical situations, the efficacy of pulsed and continuous infusion for flushing IVADs. For both of them different flow rates, flushing volumes, and times were tested. Methods The PU catheter lumens were filled with a mixture of fibronectin and bovine albumin to simulate physiologic protein depot. Flushing was performed with normal saline. An adapted pump controlled the flow rates. Efficacy was measured by the amount of albumin recovered from the lumen of the tested devices. Flow rate, volumes, and times tested were based upon values reported and/or measured in nursing practices. We compared: (A) single 10 mL bolus and 6 flushing times, (B) continuous infusion of 500 mL in 24 hours, (C) 10 successive boluses 1 mL flushed in 0.5 s each and 6 different time intervals between each bolus. Statistics were performed using the Mann and Whitney U test. Results In group A, the maximum percentage of recovered protein (79.1% was achieved with the 10 mL bolus flushed in 2.5. In group B, 77% of protein was recovered at 24h. In group C: maximum efficacy (90 +/- 3%) was obtained when the time interval between 2 boluses was 0.4 s. Conclusions We conclude that hydrodynamics has a determinant effect on the efficacy and that the adjunction of an intermittent component in the flow increases it. Flow type and the time interval between 2 boluses are the 2 critical variables.

Purpose A single center, prospective study was performed to assess the efficacy and safety of Griflow® Dual–-a gravity-fed device for intravenous delivery of human immunoglobulin Flebogamma®. Methods A total of 2 infusions in 2 visits per patient were assessed using G2 and G3 Griflow® Dual models that provide different flow rates adjusted to the patient's weight. To follow the most common method of intravenous immunoglobulin administration, infusion through the two-way device commenced with the low flow rate capillary (clamp closed) for 30 minutes and continued with the high flow rate, opening both ways. Reliability of flow delivery (average flow rates), adverse events, as well as functionality in daily practice (questionnaire to nurses) were assessed. Results twenty-five valid infusions were evaluated on 13 subjects. Except for the G2 model with closed clamp in which 14.5% deviation was observed, actual average flow rate values fell well into the maximum 10% deviation permitted with respect to expected charted values (G2: 55 and 142 mL/h; G3: 76 and 189 mL/h). Discrepancies could be explained by patient's arm movements or posture change during infusion. No adverse events related to the study device occurred. In the functionality questionnaires, nurse's comfort and safety of infusion with Griflow® Dual were rated higher than without Griflow® Dual but lower than with infusion pumps. Conclusions Although it may not be as precise as an infusion pump, Griflow® Dual proved to be a reliable and suitable device to administer Flebogamma® 5%. Correct safety should be confirmed in a larger sample.

Clinical uncertainty exists regarding which assay should be designated as the standard monitoring coagulation test for intravenous unfractionated heparin (UFH). Several studies have compared the use of activated partial thromboplastin time (aPTT) and antifactor-Xa (anti-Xa) and have come out with varying results. The correlation between these 2 tests varied, markedly from strong to weak. Some have demonstrated that monitoring with anti-Xa heparin assay leads to fewer dose adjustments, resulting in fewer laboratory tests, while others have not. In the current study, we evaluated the correlation between aPTT and anti-Xa values to guide clinical management of UFH, with the intention to develop a new correlation nomogram.

Background and aims: The objective of this study was to find out the effect of various doses of hydroxyethyl starch (HES), gelatine or Ringer’s acetate on cardiac and stroke volume index after cardiac surgery. Material and methods: Three consecutive boluses (each 7 mL·kg-1) of either 6% HES 130/0.4, 4% gelatine, or Ringer’s acetate solutions were administered to 45 patients postoperatively. The rate of infusions was adjusted according to haemodynamic measurements. Thereafter, infusion of the study solution (7 mL·kg-1) was continued for the following 12 hours. The total dose of study solution was 28 mL·kg-1. Results and conclusion: Mean (SD) cardiac and stroke volume indices were greater in the HES group [2.8 L·min-1.m-2 (0.7), 34.1 (6.7) ml·m -2] than in the gelatine group [2.2 L·min-1.m -2 (0.6), 25.8 (7.2) ml·m-2] after completion of 7 mL·kg-1 of study solution. At this stage, the effect of gelatine did not differ from Ringer’s acetate. After completion of 14 mL·kg-1 and 21 mL·kg-1 of colloids, similar cardiac and stroke volume indices were observed and the haemodynamic response was better in both colloid groups than in the Ringer’s acetate group. No differences between groups were detected on the first postoperative morning. In the early postoperative phase after cardiac surgery, the effect of a single dose of HES solution on the haemodynamics was superior to the effect of gelatine or Ringer’s acetate. However, after repeated administration of the study solutions, the haemodynamics in the two colloid groups appeared to be similar, but superior to the Ringer’s acetate group.

Aims and background The social cost of management of patients suffering from colorectal cancer has been growing dramatically in the last decade due to the high number of active antitumor agents and to the increased incidence of the tumor in western countries. The aim of the study was to explore from a pharmacoeconomic point of view a different way to administer the two most common regimens in this patient setting. Study design This was a cost-minimization study. Data were extracted from hospital registries and dedicated offices. The traditional setting (day hospital inpatient setting) and a fully ambulatory setting (CIP™ pump) were considered and compared. Results The CIP™ system resulted in higher direct costs than the day hospital setting (444.70 vs 159.00 euro/cycle). However, traditional infusion resulted in longer nursing care, with an increase in nursing costs of more than 100.00 euro/cycle. Moreover, the inpatient setting obliged patients to stay in the hospital as much as ten times longer than with the CIP™ system. This meant that with the same time span and the same resources, the CIP™ pump permitted treatment of at least five times more patients than the traditional setting. Thus, a threshold of 52.00 euro per patient for general hospital costs (ordinary and extraordinary maintenance of buildings, power supply, and housekeeping) was identified to discriminate whether the CIP™ pump is cost-saving or not. Conclusions Administration of the FOLFIRI or FOLFOX regimen in a traditional day hospital setting was less costly when considering the direct costs. However, a fully ambulatory pump permitted to better employ hospital resources and could permit cost-saving in those units in which more than five patients per day are treated and global costs are higher than 52.00 euro per patient.

Purpose To assess the efficacy of continuous bupivacaine infusion at the iliac crest donor site in reducing postoperative pain and inpatient hospital stay. Methods Forty consecutive cleft lip/palate patients who underwent alveolar bone grafting at a single institution between 2003 and 2008 were identified, and their charts were retrospectively reviewed. Opioid analgesic use, self-reported pain indices, and length of hospital stay were analyzed. Comparisons were made between those patients who received a bupivacaine infusion pump at the iliac crest harvest site and those who did not. Results Twenty patients underwent iliac crest bone graft harvest followed by intraoperative placement of a continuous 0.25% bupivacaine infusion pump, and 20 were managed primarily with postoperative intravenous and parenteral analgesics. There were no statistically significant differences in demographics between the two cohorts. Those patients receiving continuous bupivacaine had a decreased length of hospital stay (mean, 2.9 versus 1.4 days; p = .0077), a statistical trend toward decreased opioid use ( p = .032), and a lower average subjective pain score on the day of surgery ( p = .0058). Conclusion There is a significant decrease in the length of hospitalization when using a continuous local infusion pump to deliver bupivacaine to the iliac crest following bone graft harvest. The pump is tolerated by patients and carries little morbidity. As such, the benefit of reduced cost from a reduced hospital stay is worthwhile. Continuous bupivacaine infusion is recommended for the iliac crest donor site.

We developed a simple device that stabilizes the blood level in the reservoir of the extracorporeal circulation open circuit system by measuring the hydrostatic pressure of the reservoir to control the flow rate of the arterial pump. When the flow rate of the venous return decreases, the rotation speed of the arterial pump is automatically slowed down. Consequently, the blood level in the reservoir is stabilized quickly between two arbitrarily set levels and never falls below the pre-set low level. We conducted a basic experiment to verify the operation of the device, using a mock circuit with water. Commercially available pumps and reservoir were used without modification. The results confirmed that the control method effectively regulates the reservoir liquid level and is highly reliable. The device possibly also functions as a safety device.

Introduction: Centrifugal blood pumps have been widely adopted in conventional adult cardiopulmonary bypass and circulatory assist procedures. Different brands of centrifugal blood pumps incorporate distinct designs which affect pump performance. In this adult extracorporeal life support (ECLS) model, the performances of two brands of centrifugal blood pump (RotaFlow blood pump and CentriMag blood pump) were compared. Methods: The simulated adult ECLS circuit used in this study included a centrifugal blood pump, Quadrox D membrane oxygenator and Sorin adult ECLS tubing package. A Sorin Cardiovascular® VVR® 4000i venous reservoir (Sorin S.p.A., Milan, Italy) with a Hoffman clamp served as a pseudo-patient. The circuit was primed with 900ml heparinized human packed red blood cells and 300ml lactated Ringer’s solution (total volume 1200 ml, corrected hematocrit 40%). Trials were conducted at normothermia (36°C). Performance, including circuit pressure and flow rate, was measured for every setting analyzed. Results: The shut-off pressure of the RotaFlow was higher than the CentriMag at all measurement points given the same rotation speed (p < 0.0001). The shut-off pressure differential between the two centrifugal blood pumps was significant and increased given higher rotation speeds (p < 0.0001). The RotaFlow blood pump has higher maximal flow rate (9.08 ± 0.01L/min) compared with the CentriMag blood pump (8.37 ± 0.02L/min) (p < 0.0001). The blood flow rate differential between the two pumps when measured at the same revolutions per minute (RPM) ranged from 1.64L/min to 1.73L/min. Conclusions: The results obtained in this experiment demonstrate that the RotaFlow has a higher shut-off pressure (less retrograde flow) and maximal blood flow rate than the CentriMag blood pump. Findings support the conclusion that the RotaFlow disposable pump head has a better mechanical performance than the CentriMag. In addition, the RotaFlow disposable pump is 20-30 times less expensive than the CentriMag.

Background: Little is known about how the most advanced technology affects treatment satisfaction and health-related quality of life (HRQOL) in adults with diabetes. This study was designed to assess treatment satisfaction and HRQOL among users of an integrated real-time (RT) continuous glucose monitoring (CGM)/continuous subcutaneous insulin infusion (CSII) system compared with those using self-monitoring of blood glucose (SMBG) with CSII. Methods: Participants were 311 adult respondents to an Internet survey, 162 using RT-CGM/CSII, 149 using SMBG + CSII (median age 43 years; type 1 diabetes 94%; diabetes duration >15 years 61%; median insulin use 15 years). Respondents completed instruments assessing glucose monitoring system and insulin delivery system convenience, interference, burden, glucose control efficacy, cost satisfaction, overall satisfaction, and treatment preference, as well as quality of life (diabetes-related worries, social burden, and psychological well-being). Real-time CGM/CSII users also assessed specific elements of the RT-CGM/CSII system. Group differences were assessed using analysis of covariance controlling for respondent characteristics. Results: The RT-CGM/CSII group gave significantly better ratings than the SMBG + CSII group for their glucose monitoring system's glucose control efficacy, overall satisfaction, desire to switch, and willingness to recommend, and significantly worse ratings for interference with daily activities. The RT-CGM/CSII group gave significantly better ratings than the SMBG + CSII group for their insulin delivery system's convenience and glucose control efficacy, overall satisfaction, desire to switch, and willingness to recommend. Real-time CGM/CSII users gave positive ratings of all system features. Conclusions: Users of the integrated RT-CGM/CSII system reported more benefits of treatment, higher treatment satisfaction and quality of life, and greater preference for this system than SMBG + CSII users.

Juvenile rats with kaolin-induced hydrocephalus have reduced brain injury if treated with nimodipine or magnesium sulfate. Experiments were conducted to determine if the neuroprotective effects could be replicated in neonatal rats with experimental hydrocephalus at an age comparable to prematurely born humans. In a blinded and randomized manner, drugs were administered for 14 days beginning 7 days after induction of hydrocephalus. Nimodipine was given twice daily by subcutaneous injections. Daily doses greater than 38 mg/kg of body weight were fatal. Daily doses of 3.8 to 30 mg/kg were not associated with behavioral, structural, or biochemical improvements. Magnesium chloride was administered via daily subcutaneous minipump infusion (0.87 or 1.74 mM/kg) along with twice daily injections of 0.74 or 1.48 mM/kg. Magnesium sulfate was administered by twice daily subcutaneous doses of 1.54 or 7.72 mM/kg. Sedation occurred, but there was no statistically significant protection in regard to behavior, brain structure, or brain composition in any of the magnesium experiments. Developmental alterations in calcium channels of the neonatal rat brain could account for differences from prior experiments in young hydrocephalic rats.

Objective. To determine the efficacy of decreasing cardiopulmonary bypass (CPB) prime volume for neonates and small infants by using low prime oxygenators, small diameter polyvinyl chloride (PVC) tubing and removing the arterial line filter (ALF) in an effort to reduce intraoperative exposure to multiple units of packed red blood cells (PRBC). Methods. Two retrospective database studies comparing neonatal CPB prime volume were undertaken: Study 1 — A CPB circuit consisting of a 1/8 inch arterial line, a 3/16 inch venous line and a low prime oxygenator with 172 ml total circuit prime ( n = 74) was compared to a circuit with a 3/16 inch arterial line, a 1/4 inch venous line and a higher prime oxygenator with a 350 ml total circuit prime ( n = 74). Study 2 — The 172 ml circuit ( n = 389) was compared to a circuit that included an ALF and had a total circuit prime volume of 218 ml ( n = 389). Results. Study 1— of the 74 neonates and small infants whose CPB prime volume was 350 ml, 19 were exposed to two or more intraoperative exogenous PRBC units while only 3 neonates and small infants in the 172 ml prime group ( n = 74) received two or more units ( p = 0.0002). Study 2 — of the 389 neonates and small infants where an ALF was used (prime volume 218 ml), 54 were exposed to two or more exogenous PRBC units while only 36 of the 389 patients where an ALF was not used (prime volume 172 ml) received two or more units of intraoperative PRBCs ( p = 0.0436). Conclusion. Decreasing the neonatal and small infant extracorporeal circuit prime volume by as little as 46 ml resulted in significantly fewer multiple exposures to exogenous PRBC units. Perfusion (2007) 22, 327—331.

The use of a syringe driver to administer drugs by continuous subcutaneous infusion is common practice in the UK. Over time, drug combinations used in a syringe driver are likely to change and the aim of this survey was to obtain a more recent snapshot of practice. On four separate days, at two-week intervals, a questionnaire was completed for every syringe driver in use by 15 palliative care services. Of 336 syringe drivers, the majority contained either two or three drugs, but one-fifth contained only one drug. The median (range) volume of the infusions was 15 (9.5–48) mL, and duration of infusion was generally 24 hours. Only one combination was reported as visually incompatible, and there were 13 site reactions (4% of total). Laboratory physical and chemical compatibility data are available for less than half of the most frequently used combinations.

The goal of this article was to review studies comparing continuous subcutaneous insulin infusion (CSII) to multiple daily insulin injections (MDIs) in children and adolescents with type I diabetes on five parameters: glycemic control, adverse events, required insulin dosage, weight gain, and psychosocial implications. Two of the five studies (sample sizes 19-75 patients) showed that insulin pumps provided better glycemic control, fewer adverse events, and better psychosocial implications than MDIs. Three of the five showed a lower required insulin dosage in CSII and one of the five showed less weight gain with CSII. Studies 4 and 5, both done in preschoolers, showed no significant difference on any of the five parameters. The majority of the patients and families chose to continue with CSII after the completion of the studies, even in studies where insulin pumps showed no objective benefit. Insulin pumps appear to offer potential benefit over MDIs, but the efficacy, safety, and cost effectiveness of CSII versus MDIs as first-line therapy for type I diabetes in this population has not yet been clearly established. Until more data are available from large, randomized, controlled studies, MDIs may be used as first-line therapy and CSII should be considered in patients who have poor glycemic control or who are not compliant with multiple injections.

The concept that the natural history of certain heart defects could be positively modified through in utero intervention has stimulated extensive research in fetal cardiac intervention and surgery since the early 1980s. Since the management of certain defects would require the use of cardiopulmonary support, extensive studies have been directed toward the application of a variety of perfusion circuits. The unique features of the fetal patient have directed the focus of many of these designs toward miniaturization of components and minimization of prime volume. Large extracorporeal surface contact areas and prime volumes have been identified as potential contributors to a frequently observed placental dysfunction following fetal cardiopulmonary bypass (CPB). We set out to develop means of CPB using a centrifugal micro-system that would not require supplemental prime volume. We describe the unique application of an adult right heart assist device, primarily used for ‘off-pump’ coronary revascularization for fetal cardiopulmonary support. Finally, while previous fetal experiments have used late-gestation mature fetuses, we studied more immature fetuses of mid-gestation, relevant to current clinical attempts in fetal therapy.

Ketoprofen lysine salt (Artrosilene®, injectable solution) is a non-steroidal anti-inflammatory agent frequently administered by slow intravenous infusion with portable elastomeric infusion systems in association regimen with other analgesic drugs. The aim of this study was to investigate the physicochemical compatibility between ketoprofen lysine salt (Artrosilene®, injectable solution) and other injectable drugs frequently used in association, such as tramadol hydrochloride, keterolac tromethamine and morphine hydrochloride, into the Infusor LV5, Baxter elastomeric infusion system. Physicochemical properties of drug mixture, including colour, clarity, pH and drug content were observed or measured by a reversed-phase HPLC method with UV detection, before and after (up to 7 days) mixing at room temperature and under light protection. The results obtained demonstrated the physicochemical compatibility of ketoprofen lysine salt (Artrosilene®, injectable solution) with all drug formulations at every tested mixing ratios into Baxer Infusor LV5 infusion devices.

BACKGROUND Intravenous cefuroxime sodium solution could be prepared in advance by a centralized hospital pharmacy service to improve safety and time management. OBJECTIVE To investigate the effect of freezing and microwave thawing on the solution stability of cefuroxime. METHODS Cefuroxime 1.5 g in 100 mL of dextrose 5% in polyolefin bags was frozen individually (group A) or in one package (group B) for 98 days at −20 °C. The solutions were then thawed using microwaves at 270 (light cycle) or 800 watts (hard cycle) and stored at 4 °C. The cefuroxime concentration was measured by HPLC. Visual inspection was performed and pH was measured at that time. Stability of the solution was defined as a concentration remaining superior to 90% of the initial concentration by regression analysis. RESULTS No color change or precipitation in the solutions was observed. In group A, stability was at least 23 and 21 days after light and hard cycle thawing, respectively. In group B, stability was at least 21 and 18 days, respectively, with the pH increasing without affecting chromatographic parameters. CONCLUSIONS The optimal conditions for advance preparation of a solution containing cefuroxime 1.5% in dextrose 5% may be freezing of individual containers followed by a light cycle of microwave thawing.

Existing liver perfusion models are largely limited by high degrees of ischemic and reperfusion injury and the lack of standardization. To establish a highly standardized perfusion model and minimize reperfusion injury, a porcine liver perfusion model was developed using an artificial heart pump (Buecherl Artificial Heart). This model is characterized by pneumatically driven and pressure controlled blood pumps with pulsating flow characteristics. The perfusion parameters and the integrity of the perfused organ were assessed using hemodynamic and hepatic function tests. In eight porcine liver perfusion experiments the system allowed maintaining stable and physiologic organ function over 3 hours by bile production (5.5 ±3.1 ml/30 minutes, resp. 22.9 ±8.4 ml cumulative at 180 minutes), oxygen consumption (2.2 ±0.2 ml/min/100 g overall mean) and significantly better liver enzyme levels (AST 19.5 ± 10.1 U/l/100 g, ALT 2.1 ± 0.8 U/l/min, LDH 57.8 ± 24.2 U/l/100 g) compared to previous studies. It was also possible to reduce the circulating blood volume to 1,000 ml and to create a compact perfusion system that is adoptable to other organ systems such as the kidneys. The compact size and the absence of magnetic components also allow a use for advanced imaging techniques. In conclusion this optimized perfusion system provides a sound basis for future studies in the area of hepatotoxicity and pharmacology.

Osteopontin (OPN), a major non-collagenous matrix protein of bone, is also found in tissue fluids and in the circulation. It is still not clear whether circulating OPN contributes to bone formation. To elucidate this question, rat OPN was tagged with dinitrophenol groups and administered to rats either intravenously or by infusion with an osmotic minipump through a “surgical window” in the bone of the hemimandible. Dinitrophenylated rat albumin (ALB) was used as a control. The presence and distribution of tagged proteins were revealed by immunogold labeling on sections of tibia and alveolar bone. Tagged molecules of OPN were found in mineralization foci, surfaces and interfaces, and matrix accumulations among calcified collagen fibrils. Even though dinitrophenylated ALB was administered at several-fold higher concentrations, it did not accumulate in these sites. These results show that circulating OPN can be incorporated into specific compartments of forming bone and suggest that such molecules may play a more important role than previously suspected.

Pain after an open inguinal hernia repair may be significant. In fact, some surgeons feel that the pain after open repair justifies a laparoscopic approach. The purpose of this study was to determine if the use of local anesthetic infusion pumps would reduce postoperative pain after open inguinal hernia repair. We performed a prospective, double-blind randomized study of 45 open plug and patch inguinal hernia repairs. Patients were randomized to receive either 0.25 per cent bupivicaine or saline solution via an elastomeric infusion pump (ON-Q) for 48 hours, at 2 cc/h. The catheters were placed in the subcutaneous tissue and removed on postoperative day 3. Both groups were prescribed hydrocodone to use in the postoperative period at the prescribed dosage as needed for pain. Interviews were conducted on postoperative days 3 and 7, and patient's questionnaires, including pain scores, amount of pain medicine used, and any complications, were collected accordingly. During the first 5 postoperative days, postoperative pain was assessed using a visual analog scale. Twenty-three repairs were randomized to the bupivicaine group and 22 repairs randomized to the placebo group. In the bupivicaine group, there was a significant decrease in postoperative pain on postoperative days 2 through 5 with P values