[Continuous subcutaneous infusion of opioids in cancer patients].

PubMed

Galamba, J M; Olsen, A K; Crawford, M E; Sjøgren, P

1995-07-17

This review article describes pharmacokinetics, pharmaco-dynamics, side effects and the practical use of continuous subcutaneous infusion of opioids in cancer patients with pain. Clinical studies have shown that the analgesic effects of continuous subcutaneous infusion of morphine are comparable to continuous intravenous morphine, and that the treatment modality is associated with a low frequency of side-effects and complications. Continuous subcutaneous infusions of morphine are therefore recommended as the treatment of choice for cancer patients with pain, when oral analgesic treatment is no longer possible.

Randomized trial of intermittent or continuous amnioinfusion for variable decelerations.

PubMed

Rinehart, B K; Terrone, D A; Barrow, J H; Isler, C M; Barrilleaux, P S; Roberts, W E

2000-10-01

To determine whether continuous or intermittent bolus amnioinfusion is more effective in relieving variable decelerations. Patients with repetitive variable decelerations were randomized to an intermittent bolus or continuous amnioinfusion. The intermittent bolus infusion group received boluses of 500 mL of normal saline, each over 30 minutes, with boluses repeated if variable decelerations recurred. The continuous infusion group received a bolus infusion of 500 mL of normal saline over 30 minutes and then 3 mL per minute until delivery occurred. The ability of the amnioinfusion to abolish variable decelerations was analyzed, as were maternal demographic and pregnancy outcome variables. Power analysis indicated that 64 patients would be required. Thirty-five patients were randomized to intermittent infusion and 30 to continuous infusion. There were no differences between groups in terms of maternal demographics, gestational age, delivery mode, neonatal outcome, median time to resolution of variable decelerations, or the number of times variable decelerations recurred. The median volume infused in the intermittent infusion group (500 mL) was significantly less than that in the continuous infusion group (905 mL, P =.003). Intermittent bolus amnioinfusion is as effective as continuous infusion in relieving variable decelerations in labor. Further investigation is necessary to determine whether either of these techniques is associated with increased occurrence of rare complications such as cord prolapse or uterine rupture.

Analysis of the intraocular jet flows and pressure gradients induced by air and fluid infusion: mechanism of focal chorioretinal damage.

PubMed

Kim, Yong Joon; Jo, Sungkil; Moon, Daruchi; Joo, Youngcheol; Choi, Kyung Seek

2014-05-01

To comprehend the mechanism of focal chorioretinal damage by analysis of the pressure distribution and dynamic pressure induced by infused air during fluid-air exchange. A precise simulation featuring a model eye and a fluid circuit was designed to analyze fluid-air exchange. The pressure distribution, flow velocity, and dynamic pressure induced by infusion of air into an air-filled eye were analyzed using an approach based on fluid dynamics. The size of the port and the infusion pressure were varied during simulated iterations. We simulated infusion of an air-filled eye with balanced salt solution (BSS) to better understand the mechanism of chorioretinal damage induced by infused air. Infused air was projected straight toward a point on the retina contralateral to the infusion port (the "vulnerable point"). The highest pressure was evident at the vulnerable point, and the lowest pressure was recorded on most retinal areas. Simulations using greater infusion pressure and a port of larger size were associated with elevations in dynamic pressure and the pressure gradient. The pressure gradients were 2.8 and 5.1 mm Hg, respectively, when infusion pressures of 30 and 50 mm Hg were delivered through a 20-gauge port. The pressure gradient associated with BSS infusion was greater than that created by air, but lasted for only a moment. Our simulation explains the mechanism of focal chorioretinal damage in numerical terms. Infused air induces a prolonged increase in focal pressure on the vulnerable point, and this may be responsible for visual field defects arising after fluid-air exchange. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Cardiovascular Deconditioning and Venous Air Embolism in Simulated Microgravity in the Rat

NASA Technical Reports Server (NTRS)

Robinson, R. R.; Doursout, M.-F.; Chelly, J. E.; Powell, M. R.; Little, T. M.; Butler,B. D.

1996-01-01

Astronauts conducting extravehicular activities undergo decompression to a lower ambient pressure, potentially resulting in gas bubble formation within the tissues and venous circulation. Additionally, exposure to microgravity produces fluid shifts within the body leading to cardiovascular deconditioning. A lower incidence of decompression illness in actual spaceflight compared with that in ground-based altitude chamber flights suggests that there is a possible interaction between microgravity exposure and decompression illness. The purpose of this study was to evaluate the cardiovascular and pulmonary effects of simulated hypobaric decompression stress using a tail suspension (head-down tilt) model of microgravity to produce the fluid shifts associated with weightlessness in conscious, chronically instrumented rats. Venous bubble formation resulting from altitude decompression illness was simulated by a 3-h intravenous air infusion. Cardiovascular deconditioning was simulated by 96 h of head-down tilt. Heart rate, mean arterial blood pressure, central venous pressure, left ventricular wall thickening and cardiac output were continuously recorded. Lung studies were performed to evaluate edema formation and compliance measurement. Blood and pleural fluid were examined for changes in white cell counts and protein concentration. Our data demonstrated that in tail-suspended rats subjected to venous air infusions, there was a reduction in pulmonary edema formation and less of a decrease in cardiac output than occurred following venous air infusion alone. Mean arterial blood pressure and myocardial wall thickening fractions were unchanged with either tail-suspension or venous air infusion. Heart rate decreased in both conditions while systemic vascular resistance increased. These differences may be due in part to a change or redistribution of pulmonary blood flow or to a diminished cellular response to the microvascular insult of the venous air embolization.

The predictive ability of six pharmacokinetic models of rocuronium developed using a single bolus: evaluation with bolus and continuous infusion regimen.

PubMed

Sasakawa, Tomoki; Masui, Kenichi; Kazama, Tomiei; Iwasaki, Hiroshi

2016-08-01

Rocuronium concentration prediction using pharmacokinetic (PK) models would be useful for controlling rocuronium effects because neuromuscular monitoring throughout anesthesia can be difficult. This study assessed whether six different compartmental PK models developed from data obtained after bolus administration only could predict the measured plasma concentration (Cp) values of rocuronium delivered by bolus followed by continuous infusion. Rocuronium Cp values from 19 healthy subjects who received a bolus dose followed by continuous infusion in a phase III multicenter trial in Japan were used retrospectively as evaluation datasets. Six different compartmental PK models of rocuronium were used to simulate rocuronium Cp time course values, which were compared with measured Cp values. Prediction error (PE) derivatives of median absolute PE (MDAPE), median PE (MDPE), wobble, divergence absolute PE, and divergence PE were used to assess inaccuracy, bias, intra-individual variability, and time-related trends in APE and PE values. MDAPE and MDPE values were acceptable only for the Magorian and Kleijn models. The divergence PE value for the Kleijn model was lower than -10 %/h, indicating unstable prediction over time. The Szenohradszky model had the lowest divergence PE (-2.7 %/h) and wobble (5.4 %) values with negative bias (MDPE = -25.9 %). These three models were developed using the mixed-effects modeling approach. The Magorian model showed the best PE derivatives among the models assessed. A PK model developed from data obtained after single-bolus dosing can predict Cp values during bolus and continuous infusion. Thus, a mixed-effects modeling approach may be preferable in extrapolating such data.

Treatment of severe cancer pain by low-dose continuous subcutaneous morphine.

PubMed

Drexel, H; Dzien, A; Spiegel, R W; Lang, A H; Breier, C; Abbrederis, K; Patsch, J R; Braunsteiner, H

1989-02-01

In a prospective and intraindividually controlled trial, we have compared the efficacy and safety of a continuous subcutaneous morphine infusion with conventional intermittent oral or subcutaneous morphine application. Twenty-eight in-patients with cancer pain received a short-term infusion lasting 2-42 days, and 8 out-patients underwent long-term infusion from 49 to 197 days during the terminal stage of their disease. Continuous subcutaneous morphine infusion significantly (P less than 0.001) improved both pain and quality of life when compared to conventional morphine application. With continuous infusion, 5-48 mg (median 19 mg) of morphine was required daily, significantly (P less than 0.001) less than the 10-90 mg (median 50 mg) necessary with conventional use. As a result of lower dosage, side effects under continuous infusion were infrequent and mild. Constipation occurred in 3 of the 36 patients and was always controlled by the addition of laxatives; no nausea, sedation or respiratory depression were observed. Signs of tolerance developed in 2 patients on long-term infusion, but the use of continuous subcutaneous methadone for 2 weeks reversed the tolerance. The study presented indicates that low-dose continuous subcutaneous morphine provides a valuable treatment modality for severe terminal cancer pain exhibiting a high degree of both efficacy and safety.

Effect of coefficient of viscosity and ambient temperature on the flow rate of drug solutions in infusion pumps.

PubMed

Kawabata, Yoshinori

2012-01-01

FOLFOX6 and FOLFIRI regimens are often selected as the first- or second-line treatment for advanced or recurrent colorectal cancer. Patients are now able to undergo at-home treatment by using a portable disposable infusion pump (SUREFUSER(®)A) for continuous intravenous infusion of 5-fluorouracil (5-FU). The duration of continuous 5-FU infusion is normally set at an average of 46 h, but large variations in the duration of infusion are observed. The relationship between the total volume of the drug solution in SUREFUSER(®)A and the duration of infusion was analyzed by regression analysis. In addition, multiple regression analysis of the total volume of the drug solution, dummy variables for temperature, and duration of infusion was carried out. The duration of infusion was affected by the coefficient of viscosity of the drug solution and the ambient temperature. The composition of the drug solutions and the ambient temperature must be considered to ensure correct duration of continuous infusion.

Influences of brain tissue poroelastic constants on intracranial pressure (ICP) during constant-rate infusion.

PubMed

Li, Xiaogai; von Holst, Hans; Kleiven, Svein

2013-01-01

A 3D finite element (FE) model has been developed to study the mean intracranial pressure (ICP) response during constant-rate infusion using linear poroelasticity. Due to the uncertainties in the poroelastic constants for brain tissue, the influence of each of the main parameters on the transient ICP infusion curve was studied. As a prerequisite for transient analysis, steady-state simulations were performed first. The simulated steady-state pressure distribution in the brain tissue for a normal cerebrospinal fluid (CSF) circulation system showed good correlation with experiments from the literature. Furthermore, steady-state ICP closely followed the infusion experiments at different infusion rates. The verified steady-state models then served as a baseline for the subsequent transient models. For transient analysis, the simulated ICP shows a similar tendency to that found in the experiments, however, different values of the poroelastic constants have a significant effect on the infusion curve. The influence of the main poroelastic parameters including the Biot coefficient α, Skempton coefficient B, drained Young's modulus E, Poisson's ratio ν, permeability κ, CSF absorption conductance C(b) and external venous pressure p(b) was studied to investigate the influence on the pressure response. It was found that the value of the specific storage term S(ε) is the dominant factor that influences the infusion curve, and the drained Young's modulus E was identified as the dominant parameter second to S(ε). Based on the simulated infusion curves from the FE model, artificial neural network (ANN) was used to find an optimised parameter set that best fit the experimental curve. The infusion curves from both the FE simulation and using ANN confirmed the limitation of linear poroelasticity in modelling the transient constant-rate infusion.

Continuous subcutaneous administration of the N-methyl-D-aspartic acid (NMDA) receptor antagonist ketamine in the treatment of post-herpetic neuralgia.

PubMed

Eide, K; Stubhaug, A; Oye, I; Breivik, H

1995-05-01

The effect of continuous subcutaneous (s.c.) infusion of ketamine on nerve injury pain was examined in patients with post-herpetic neuralgia. Five patients that reported pain relief after acute intravenous injection of ketamine were included in this open prospective study. Ketamine was administered continuously in increasing doses using a portable infusion pump (CADD-PLUS, Pharmacia), and the treatment period for each infusion rate (0.05, 0.075, 0.10, or 0.15 mg/kg/h) was 7 days and nights. Relief of continuous pain, as evaluated daily by visual analogue scales, was observed at the infusion rate of 0.05 mg/kg/h, but was most marked during infusion of 0.15 mg/kg/h. All the patients reported that ketamine reduced the severity of continuous pain as well as reduced the severity and number of attacks of spontaneous pain. Changes in evoked pain (allodynia and wind-up-like pain) were recorded before change of infusion rate. Allodynia was maximally reduced 59-100% after 1 week infusion of 0.05 mg/kg/h, and wind-up-like pain was maximally reduced 60-100% after 1 week infusion of 0.15 mg/kg/h. Itching and painful indurations at the injection site was the most bothersome side-effect and for this reason 1 patient discontinued treatment after 2 weeks. Other common side-effects were nausea, fatigue and dizziness. The present results show that continuous, spontaneous and evoked pain in patients with post-herpetic neuralgia is reduced by continuous s.c. infusion of ketamine, but is associated with intolerable side effects.

Continuous subcutaneous insulin infusion in diabetes: patient populations, safety, efficacy, and pharmacoeconomics

PubMed Central

Battelino, Tadej; Danne, Thomas; Hovorka, Roman; Jarosz‐Chobot, Przemyslawa; Renard, Eric

2015-01-01

Summary The level of glycaemic control necessary to achieve optimal short‐term and long‐term outcomes in subjects with type 1 diabetes mellitus (T1DM) typically requires intensified insulin therapy using multiple daily injections or continuous subcutaneous insulin infusion. For continuous subcutaneous insulin infusion, the insulins of choice are the rapid‐acting insulin analogues, insulin aspart, insulin lispro and insulin glulisine. The advantages of continuous subcutaneous insulin infusion over multiple daily injections in adult and paediatric populations with T1DM include superior glycaemic control, lower insulin requirements and better health‐related quality of life/patient satisfaction. An association between continuous subcutaneous insulin infusion and reduced hypoglycaemic risk is more consistent in children/adolescents than in adults. The use of continuous subcutaneous insulin infusion is widely recommended in both adult and paediatric T1DM populations but is limited in pregnant patients and those with type 2 diabetes mellitus. All available rapid‐acting insulin analogues are approved for use in adult, paediatric and pregnant populations. However, minimum patient age varies (insulin lispro: no minimum; insulin aspart: ≥2 years; insulin glulisine: ≥6 years) and experience in pregnancy ranges from extensive (insulin aspart, insulin lispro) to limited (insulin glulisine). Although more expensive than multiple daily injections, continuous subcutaneous insulin infusion is cost‐effective in selected patient groups. This comprehensive review focuses on the European situation and summarises evidence for the efficacy and safety of continuous subcutaneous insulin infusion, particularly when used with rapid‐acting insulin analogues, in adult, paediatric and pregnant populations. The review also discusses relevant European guidelines; reviews issues that surround use of this technology; summarises the effects of continuous subcutaneous insulin infusion on patients' health‐related quality of life; reviews relevant pharmacoeconomic data; and discusses recent advances in pump technology, including the development of closed‐loop ‘artificial pancreas’ systems. © 2015 The Authors. Diabetes/Metabolism Research and Reviews Published by John Wiley & Sons Ltd. PMID:25865292

Radiofrequency ablation during continuous saline infusion can extend ablation margins

PubMed Central

Ishikawa, Toru; Kubota, Tomoyuki; Horigome, Ryoko; Kimura, Naruhiro; Honda, Hiroki; Iwanaga, Akito; Seki, Keiichi; Honma, Terasu; Yoshida, Toshiaki

2013-01-01

AIM: To determine whether fluid injection during radiofrequency ablation (RFA) can increase the coagulation area. METHODS: Bovine liver (1-2 kg) was placed on an aluminum tray with a return electrode affixed to the base, and the liver was punctured by an expandable electrode. During RFA, 5% glucose; 50% glucose; or saline fluid was infused continuously at a rate of 1.0 mL/min through the infusion line connected to the infusion port. The area and volume of the thermocoagulated region of bovine liver were determined after RFA. The Joule heat generated was determined from the temporal change in output during the RFA experiment. RESULTS: No liquid infusion was 17.3 ± 1.6 mL, similar to the volume of a 3-cm diameter sphere (14.1 mL). Mean thermocoagulated volume was significantly larger with continuous infusion of saline (29.3 ± 3.3 mL) than with 5% glucose (21.4 ± 2.2 mL), 50% glucose (16.5 ± 0.9 mL) or no liquid infusion (17.3 ± 1.6 mL). The ablated volume for RFA with saline was approximately 1.7-times greater than for RFA with no liquid infusion, representing a significant difference between these two conditions. Total Joule heat generated during RFA was highest with saline, and lowest with 50% glucose. CONCLUSION: RFA with continuous saline infusion achieves a large ablation zone, and may help inhibit local recurrence by obtaining sufficient ablation margins. RFA during continuous saline infusion can extend ablation margins, and may be prevent local recurrence. PMID:23483097

Closed-loop Continuous Infusions of Etomidate and Etomidate Analogs in Rats

PubMed Central

Cotten, Joseph F.; Le Ge, Ri; Banacos, Natalie; Pejo, Ervin; Husain, S. Shaukat; Williams, James H.; Raines, Douglas E.

2012-01-01

Background Etomidate is a sedative–hypnotic that is often given as a single intravenous bolus but rarely as an infusion because it suppresses adrenocortical function. Methoxycarbonyl etomidate and (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (carboetomidate) are etomidate analogs that do not produce significant adrenocortical suppression when given as a single bolus. However, the effects of continuous infusions on adrenocortical function are unknown. In this study, we compared the effects of continuous infusions of etomidate, methoxycarbonyl etomidate, and carboetomidate on adrenocortical function in a rat model. Methods A closed-loop system using the electroencephalographic burst suppression ratio as the feedback was used to administer continuous infusions of etomidate, methoxycarbonyl etomidate, or carboetomidate to Sprague–Dawley rats. Adrenocortical function was assessed during and after infusion by repetitively administering adrenocorticotropic hormone 1–24 and measuring serum corticosterone concentrations every 30 min. Results The sedative–hypnotic doses required to maintain a 40% burst suppression ratio in the presence of isoflurane, 1%, and the rate of burst suppression ratio recovery on infusion terminationvaried(methoxycarbonyletomidate>carboetomidate > etomidate). Serum corticosterone concentrations were reduced by 85% and 56% during 30-min infusions of etomidate and methoxycarbonyl etomidate, respectively. On infusion termination, serum corticosterone concentrations recovered within 30 min with methoxycarbonyl etomidate but persisted beyond an hour with etomidate. Carboetomidate had no effect on serum corticosterone concentrations during or after continuous infusion. Conclusions Our results suggest that methoxycarbonyl etomidate and carboetomidate may have clinical utility as sedative–hypnotic maintenance agents when hemodynamic stability is desirable. PMID:21572317

Continuous Intravenous Sub-Dissociative Dose Ketamine Infusion for Managing Pain in the Emergency Department

PubMed Central

Drapkin, Jefferson; Likourezos, Antonios; Beals, Tyler; Monfort, Ralph; Fromm, Christian; Marshall, John

2018-01-01

Introduction Our objective was to describe dosing, duration, and pre- and post-infusion analgesic administration of continuous intravenous sub-dissociative dose ketamine (SDK) infusion for managing a variety of painful conditions in the emergency department (ED). Methods We conducted a retrospective chart review of patients aged 18 and older presenting to the ED with acute and chronic painful conditions who received continuous SDK infusion in the ED for a period over six years (2010–2016). Primary data analyses included dosing and duration of infusion, rates of pre- and post-infusion analgesic administration, and final diagnoses. Secondary data included pre- and post-infusion pain scores and rates of side effects. Results A total of 104 patients were enrolled in the study. Average dosing of SDK infusion was 11.26 mg/hr, and the mean duration of infusion was 135.87 minutes. There was a 38% increase in patients not requiring post-infusion analgesia. The average decrease in pain score was 5.04. There were 12 reported adverse effects, with nausea being the most prevalent. Conclusion Continuous intravenous SDK infusion has a role in controlling pain of various etiologies in the ED with a potential to reduce the need for co-analgesics or rescue analgesic administration. There is a need for more robust, prospective, randomized trials that will further evaluate the analgesic efficacy and safety of this modality across a wide range of pain syndromes and different age groups in the ED. PMID:29760856

[Continuous drug infusion in terminal cancer].

PubMed

Ottesen, S; Manger, A T; Monrad, L

1992-05-30

Today's technology provides portable pumps which facilitate continuous infusion of drugs to relieve suffering in terminal disease. Subcutaneous and epidural infusion is now frequently used in our hospital. The most common indications are gastrointestinal obstruction, impaired absorption of drugs, refractory side effects of oral medication or poor compliance because good pain relief is no longer possible orally. During the last days of life, this method may be the only possible approach to good comfort and relief from terminal agitation and anxiety. Of the patients referred to the advisory group for seriously ill and dying in 1990, 64% received subcutaneous infusions and 15% epidural infusions during the last days or weeks of life. Continuous infusion of drugs from portable pumps has become an almost indispensible method of treatment in an ordinary clinic.

[Successful management of neurosurgical procedures with continuous infusion of recombinant factor IX in a child with hemophilia B].

PubMed

Yamamoto, Mariko; Nakadate, Hisaya; Iguchi, Umefumi; Masuda, Hiroshi; Sakai, Hirokazu; Ishiguro, Akira

2013-03-01

This report describes the successful management of neurosurgical procedures with continuous infusion of recombinant factor IX (rFIX). A 1-year-old boy with severe hemophilia B was administered prophylactic therapy with rFIX after intracranial bleeding. We found the enlargement of an arachnoid cyst in a follow-up CT scan. He underwent marsupialization of the cyst under the continuous infusion of rFIX. FIX levels were examined in our hospital and the rFIX infusion rate was adjusted in an attempt to keep FIX levels above 90% intraoperatively, and 70% until his 7th post-operative day. We studied the pharmacokinetic profile of rFIX and found a half-time of 25 hours and mean in vivo recovery of 0.69 IU/dl/IU/kg. Reconstituted rFIX also retained at least 95% activity after 72 hours at room temperature. This is the first report of the perioperative management of a child undergoing a neurosurgical procedure under the continuous infusion of rFIX in Japan. Further studies are required before the routine use of this product for continuous infusion.

Continuous subcutaneous insulin infusion versus multiple daily injections in individuals with type 1 diabetes: a systematic review and meta-analysis.

PubMed

Benkhadra, Khalid; Alahdab, Fares; Tamhane, Shrikant U; McCoy, Rozalina G; Prokop, Larry J; Murad, Mohammad Hassan

2017-01-01

The relative efficacy of continuous subcutaneous insulin infusion and multiple daily injections in individuals with type 1 diabetes is unclear. We sought to synthesize the existing evidence about the effect of continuous subcutaneous insulin infusion on glycosylated hemoglobin, hypoglycemic events, and time spent in hypoglycemia compared to multiple daily injections. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, and Scopus from January 2008 through November 2015 for randomized controlled trials that enrolled children or adults with type 1 diabetes. Trials identified in a previous systematic review and published prior to 2008 were also included. We included 25 randomized controlled trials at moderate risk of bias. Meta-analysis showed a significant reduction in glycosylated hemoglobin in patients treated with continuous subcutaneous insulin infusion compared to multiple daily injections (mean difference 0.37; 95 % confidence interval, 0.24-0.51). This effect was demonstrated in both children and adults. There was no significant difference in minor or severe hypoglycemic events. Continuous subcutaneous insulin infusion was associated with lower incidence of nocturnal hypoglycemia. There was no significant difference in the time spent in hypoglycemia. In children and adults with type 1 diabetes and compared to multiple daily injections, continuous subcutaneous insulin infusion is associated with a modest reduction in glycosylated hemoglobin. There was no difference in severe or minor hypoglycemia, but likely a lower incidence of nocturnal hypoglycemia with continuous subcutaneous insulin infusion.

Administration of drugs by infusion pumps in palliative medicine.

PubMed

Thorsen, A B; Yung, N S; Leung, A C

1994-03-01

A retrospective study was carried out in 100 adult patients with advanced malignant disease. They were given subcutaneous continuous infusions of medication for symptom relief. The drugs were administered through a butterfly needle inserted subcutaneously in the anterior chest wall using a battery-operated infusion pump. The indications for using this technique were inability to swallow due to deteriorating general condition, oesophageal obstruction, intestinal obstruction, severe nausea and vomiting, terminal dyspnoea and poor pain control with oral opiates. All patients received morphine; other drugs administered through the syringe driver included hyoscine, metoclopramide, cyclizine, dexamethasone and midazolam. Ninety-four patients continued subcutaneous infusion until death. The mean duration of treatment was 9.1 days. The treatment was well tolerated by the patients and controlled their symptoms satisfactorily in the great majority. The use of continuous subcutaneous infusion via a syringe driver gives good symptom control. In the last days of life when the patients have difficulty tolerating oral medication, continuous subcutaneous infusion is a superior alternative to frequent intermittent parenteral injections.

[Usefulness of Bolus Administration Using the FLEX Mode(Bolus Infusion Mode)for Baclofen Tolerance].

PubMed

Tanaka, Kazunori

2017-02-01

Intrathecal baclofen(ITB)is used to treat intractable spasticity of various etiologies and can provide better control of spasticity through the adjustment of the dose administered through the pump. However, in patients who develop tolerance to baclofen with the standard simple continuous mode, a sharp increase in dose becomes necessary, and spasticity can become harder to control. We investigated whether switching from the simple continuous mode to the bolus infusion mode was effective in controlling spasticity in patients with baclofen tolerance. We reported four patients undergoing ITB therapy at our facility who were considered to have developed baclofen tolerance. We observed the number of bolus infusions and total dose suitable for maintaining spasticity control after switching from the simple continuous mode to the bolus infusion mode. After switching to the bolus infusion mode, the total dose could be reduced in the short term; however, in the long term, the frequency of bolus infusions had to be increased to maintain spasticity control. Two years after changing to bolus infusion six times a day, the total dose was higher than that in the simple continuous mode for two of the four patients, and was the same level in the other two patients. Our four cases suggest that bolus infusion is effective in patients with baclofen tolerance during ITB therapy. Therefore, the conditions of bolus infusion should be further investigated.

Infusing Social Justice in Undergraduate Nursing Education: Fostering Praxis Through Simulation.

PubMed

Caldwell, Robyn; Cochran, Courtney

Forensic clinical experiences are often inconsistent in undergraduate nursing education. Nursing students are not included in the process of forensic evidence collection, often because of the sensitive nature of the situation. Unfortunately, nursing students are forced to rely on theoretical knowledge provided by the nurse educator to understand the complexities of forensic nursing care. Nursing students must be able to identify and provide appropriate nursing care for individuals in all forensic situations. Comprehensive clinical laboratory experiences should be provided through active teaching-learning strategies, which replicate nursing care of the forensic patient. Simulated patient experiences provide a unique opportunity to explore the sensitive nature of sexual trauma in a safe learning environment. This strategy facilitates the application of theoretical forensic principles by utilizing live actors or high-fidelity manikins in laboratory settings. The application of theory to each simulated patient infuses conceptual knowledge at the point of care. Change in social consciousness begins at the bedside. The moral imperative of nursing continues to be the preparation of socially responsible, professional nurses who strive to end social injustices.

Continuous subcutaneous insulin infusion in diabetes: patient populations, safety, efficacy, and pharmacoeconomics.

PubMed

Pozzilli, Paolo; Battelino, Tadej; Danne, Thomas; Hovorka, Roman; Jarosz-Chobot, Przemyslawa; Renard, Eric

2016-01-01

The level of glycaemic control necessary to achieve optimal short-term and long-term outcomes in subjects with type 1 diabetes mellitus (T1DM) typically requires intensified insulin therapy using multiple daily injections or continuous subcutaneous insulin infusion. For continuous subcutaneous insulin infusion, the insulins of choice are the rapid-acting insulin analogues, insulin aspart, insulin lispro and insulin glulisine. The advantages of continuous subcutaneous insulin infusion over multiple daily injections in adult and paediatric populations with T1DM include superior glycaemic control, lower insulin requirements and better health-related quality of life/patient satisfaction. An association between continuous subcutaneous insulin infusion and reduced hypoglycaemic risk is more consistent in children/adolescents than in adults. The use of continuous subcutaneous insulin infusion is widely recommended in both adult and paediatric T1DM populations but is limited in pregnant patients and those with type 2 diabetes mellitus. All available rapid-acting insulin analogues are approved for use in adult, paediatric and pregnant populations. However, minimum patient age varies (insulin lispro: no minimum; insulin aspart: ≥2 years; insulin glulisine: ≥6 years) and experience in pregnancy ranges from extensive (insulin aspart, insulin lispro) to limited (insulin glulisine). Although more expensive than multiple daily injections, continuous subcutaneous insulin infusion is cost-effective in selected patient groups. This comprehensive review focuses on the European situation and summarises evidence for the efficacy and safety of continuous subcutaneous insulin infusion, particularly when used with rapid-acting insulin analogues, in adult, paediatric and pregnant populations. The review also discusses relevant European guidelines; reviews issues that surround use of this technology; summarises the effects of continuous subcutaneous insulin infusion on patients' health-related quality of life; reviews relevant pharmacoeconomic data; and discusses recent advances in pump technology, including the development of closed-loop 'artificial pancreas' systems. © 2015 The Authors. Diabetes/Metabolism Research and Reviews Published by John Wiley & Sons Ltd. © 2015 The Authors. Diabetes/Metabolism Research and Reviews Published by John Wiley & Sons Ltd.

Propylene glycol accumulation in critically ill patients receiving continuous intravenous lorazepam infusions.

PubMed

Horinek, Erica L; Kiser, Tyree H; Fish, Douglas N; MacLaren, Robert

2009-12-01

Lorazepam is recommended by the Society of Critical Care Medicine as the preferred agent for sedation of critically ill patients. Intravenous lorazepam contains propylene glycol, which has been associated with toxicity when high doses of lorazepam are administered. To evaluate the accumulation of propylene glycol in critically ill patients receiving lorazepam by continuous infusion and determine factors associated with propylene glycol concentration. A 6-month, retrospective, safety assessment was conducted of adults admitted to the medical intensive care unit who were receiving lorazepam by continuous infusion for 12 hours or more. Propylene glycol serum concentrations were obtained 24-48 hours after continuous-infusion lorazepam was initiated and every 3-5 days thereafter. Propylene glycol accumulation was defined as concentrations of 25 mg/dL or more. Groups with and without propylene glycol accumulation were compared and factors associated with propylene glycol concentration were determined using multivariate correlation regression analyses. Forty-eight propylene glycol serum samples were obtained from 33 patients. Fourteen (42%) patients had propylene glycol accumulation, representing 23 (48%) serum samples. Univariate analyses showed the following factors were related to propylene glycol accumulation: baseline renal dysfunction, presence of alcohol withdrawal, sex, age, Acute Physiology and Chronic Health Evaluation (APACHE II) score, rate of lorazepam continuous infusion, and 24-hour lorazepam dose. Multivariate linear regression modeling demonstrated that propylene glycol concentration was strongly associated with the continuous infusion rate and 24-hour dose (adjusted r(2) > or = 0.77; p < 0.001). Independent correlation analyses showed that these 2 variables were so strongly associated with propylene glycol concentration (r(2) > or = 0.71; p < 0.001) that they alone predicted propylene glycol concentration. Seven (21%) patients developed renal dysfunction after continuous-infusion lorazepam was initiated, but associated causes were indeterminable. Other possible propylene glycol-associated adverse effects were not observed. The continuous infusion rate and cumulative 24-hour lorazepam dose are strongly associated with and independently predict propylene glycol concentrations. Despite the absence of confirmed propylene glycol-associated adverse effects, clinicians should be aware that propylene glycol accumulation may occur with continuous-infusion lorazepam.

Materials Characterisation and Analysis for Flow Simulation of Liquid Resin Infusion

NASA Astrophysics Data System (ADS)

Sirtautas, J.; Pickett, A. K.; George, A.

2015-06-01

Liquid Resin Infusion (LRI) processes including VARI and VARTM have received increasing attention in recent years, particularly for infusion of large parts, or for low volume production. This method avoids the need for costly matched metal tooling as used in Resin Transfer Moulding (RTM) and can provide fast infusion if used in combination with flow media. Full material characterisation for LRI analysis requires models for three dimensional fabric permeability as a function of fibre volume content, fabric through-thickness compliance as a function of resin pressure, flow media permeability and resin viscosity. The characterisation of fabric relaxation during infusion is usually determined from cyclic compaction tests on saturated fabrics. This work presents an alternative method to determine the compressibility by using LRI flow simulation and fitting a model to experimental thickness measurements during LRI. The flow media is usually assumed to have isotropic permeability, but this work shows greater simulation accuracy from combining the flow media with separation plies as a combined orthotropic material. The permeability of this combined media can also be determined by fitting the model with simulation to LRI flow measurements. The constitutive models and the finite element solution were validated by simulation of the infusion of a complex aerospace demonstrator part.

Discontinuing Oxytocin Infusion in the Active Phase of Labor: A Systematic Review and Meta-analysis.

PubMed

Saccone, Gabriele; Ciardulli, Andrea; Baxter, Jason K; Quiñones, Joanne N; Diven, Liany C; Pinar, Bor; Maruotti, Giuseppe Maria; Martinelli, Pasquale; Berghella, Vincenzo

2017-11-01

To evaluate the benefits and harms of discontinuation of oxytocin after the active phase of labor is reached. Electronic databases (ie, MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, ScienceDirect, the Cochrane Library at the CENTRAL Register of Controlled Trials, Scielo) were searched from their inception until April 2017. We included all randomized controlled trials comparing discontinuation (ie, intervention group) and continuation (ie, control group) of oxytocin infusion after the active phase of labor is reached, either after induction or augmentation of labor. Discontinuation of oxytocin infusion was defined as discontinuing oxytocin infusion when the active phase of labor was achieved. Continuation of oxytocin infusion was defined as continuing oxytocin infusion until delivery. Only trials in singleton gestations with vertex presentation at term were included. The primary outcome was the incidence of cesarean delivery. Nine randomized controlled trials, including 1,538 singleton gestations, were identified as relevant and included in the meta-analysis. All nine trials included only women undergoing induction of labor. In the discontinuation group, if arrest of labor occurred, usually defined as no cervical dilation in 2 hours or inadequate uterine contractions for 2 hours or more, oxytocin infusion was restarted. Women in the control group had oxytocin continued until delivery usually at the same dose used at the time the active phase was reached. Women who were randomized to have discontinuation of oxytocin infusion after the active phase of labor was reached had a significantly lower risk of cesarean delivery (9.3% compared with 14.7%; relative risk 0.64, 95% CI 0.48-0.87) and of uterine tachysystole (6.2% compared with 13.1%; relative risk 0.53, 95% CI 0.33-0.84) compared with those who were randomized to have continuation of oxytocin infusion until delivery. Discontinuation of oxytocin infusion was associated with an increase in the duration of the active phase of labor (mean difference 27.65 minutes, 95% CI 3.94-51.36). In singleton gestations with cephalic presentation at term undergoing induction, discontinuation of oxytocin infusion after the active phase of labor at approximately 5 cm is reached reduces the risk of cesarean delivery and of uterine tachysystole compared with continuous oxytocin infusion. Given this evidence, discontinuation of oxytocin infusion once the active stage of labor is established in women being induced should be considered as an alternative management plan.

Recombinant FVIIa (NovoSeven) continuous infusion and total hip replacement in patients with haemophilia and high titre of inhibitors to FVIII: experience of two cases.

PubMed

Tagariello, G; De Biasi, E; Gajo, G B; Risato, R; Radossi, P; Davoli, P G; Traldi, A

2000-09-01

In this report we describe our experience of total hip replacement in two patients with severe haemophilia A and high titres of inhibitors to FVIII. We used rFVIIa replacement therapy by continuous infusion to perform the surgery. The total amount of rFVIIa used in these two patients was very similar but the manner of administration was quite different. In our experience, it is an advantage to use a higher dose for shorter periods than a lower dose for a longer treatment period. Tranexamic acid by continuous infusion, and parallel saline infusion were useful for good haemostasis and avoided local thrombophlebitis in the side of rFVIIa infusion.

Continuous wound infusion and local infiltration analgesia for postoperative pain and rehabilitation after total hip arthroplasty.

PubMed

Fusco, Pierfrancesco; Cofini, Vincenza; Petrucci, Emiliano; Scimia, Paolo; Fiorenzi, Maurizio; Paladini, Giuseppe; Behr, Astrid U; Borghi, Battista; Flamini, Stefano; Pizzoferrato, Renzo; Colafarina, Olivo; Di Francesco, Alexander; Tabacco, Tito; Necozione, Stefano; Marinangeli, Franco

2018-05-01

Total hip arthroplasty is one of the most common procedures in orthopedic surgery. We hypothesized that local infiltration of analgesia and continuous wound infusion of anesthetics in the first 72 hours after surgery could provide more effective postoperative analgesia with better rehabilitation. A double-blind, randomized, controlled study was conducted with 96 patients who underwent total hip arthroplasty. The patients were randomized to receive either a local infiltration analgesia and continuous wound infusion of anesthetics or a local infiltration analgesia and continuous wound infusion of saline solution. The patients in both groups received subarachnoid anesthesia and a local infiltration analgesia. A multihole catheter was placed next to the implant and connected to an electronic pump containing a 300-mL solution of 0.2% levobupivacaine (experimental group) or saline (control group). A total of 96 consecutive patients were enrolled and randomized. Of these, 48 patients received local infiltration analgesia and continuous wound infusion of local anesthetics, and the remainder received local infiltration analgesia and continuous wound infusion of saline solution. The analysis showed a significant main effect of treatment on the postoperative incident of pain (Ftreat(1,93)=22.62, P=0.000) and on resting pain during the post-surgery follow-up (Ftreat(1,93)=15.62, P=0.0002). The pain scores during the rehabilitation period were significantly less in the experimental group. Analgesic consumption was less in the experimental group. The addition of continuous wound infusion of anesthetics to local infiltration analgesia provided an extended analgesic effect associated with good rehabilitation performance.

Lack of difference between continuous versus intermittent heparin infusion on maintenance of intra-arterial catheter in postoperative pediatric surgery: a randomized controlled study

PubMed Central

Witkowski, Maria Carolina; de Moraes, Maria Antonieta P.; Firpo, Cora Maria F.

2013-01-01

OBJECTIVE: To compare two systems of arterial catheters maintenance in postoperative pediatric surgery using intermittent or continuous infusion of heparin solution and to analyze adverse events related to the site of catheter insertion and the volume of infused heparin solution. METHODS: Randomized control trial with 140 patients selected for continuous infusion group (CIG) and intermittent infusion group (IIG). The variables analyzed were: type of heart disease, permanence time and size of the catheter, insertion site, technique used, volume of heparin solution and adverse events. The descriptive variables were analyzed by Student's t-test and the categorical variables, by chi-square test, being significant p<0.05. RESULTS: The median age was 11 (0-22) months, and 77 (55%) were females. No significant differences between studied variables were found, except for the volume used in CIG (12.0±1.2mL/24 hours) when compared to IIG (5.3±3.5mL/24 hours) with p<0.0003. CONCLUSIONS: The continuous infusion system and the intermittent infusion of heparin solution can be used for intra-arterial catheters maintenance in postoperative pediatric surgery, regardless of patient's clinical and demographic characteristics. Adverse events up to the third postoperative day occurred similarly in both groups. However, the intermittent infusion system usage in underweight children should be considered, due to the lower volume of infused heparin solution [ClinicalTrials.gov Identifier: NCT01097031]. PMID:24473958

Pharmacokinetics and a simulation model of colforsin daropate, new forskolin derivative inotropic vasodilator, in patients undergoing coronary artery bypass grafting.

PubMed

Kikura, Mutsuhito; Morita, Koji; Sato, Shigehito

2004-03-01

Colforsin daropate, a water-soluble forskolin derivative, is an adenyl cyclase activator with positive inotropic and vasodilatory effects that are useful in the treatment of ventricular dysfunction. We investigated the pharmacokinetics of colforsin daropate in cardiac surgery patients and performed simulations to determine the dosage necessary to maintain an effective plasma concentration following cardiopulmonary bypass. In six patients undergoing coronary artery bypass graft, colforsin daropate (0.01mgkg(-1)) was administered immediately after separation from cardiopulmonary bypass. Arterial blood was sampled over the next 16h and plasma concentrations of colforsin daropate and its initial active metabolite were determined by gas-chromatography. Extended nonlinear least-squares regression was used to fit a three-compartment model to each patient's data. Distribution half-life (t(1/2alpha)) was 3.9+/-1.1min, metabolic half-life (t(1/2beta)) was 1.9+/-0.7h, and elimination half-life (t(1/2gamma)) was 95.3+/-15.2h. Central-compartment volume was 591.0+/-42.8mlkg(-1), volume distribution was 2689.2+/-450.6mlkg(-1), and elimination clearance was 27.7+/-14.7mlkg(-1)min(-1). In the pharmacokinetic simulation model, 0.5, 0.75, and 1.0microgkg(-1)min(-1) continuous infusion of colforsin daropate produce effective concentration (5-10ngml(-1)) within 30, 20, and 10min, respectively following administration. An initial active metabolite of decreased rapidly to less than 1.0ngml(-1) within the first 10min.A colforsin daropate infusion of 0.7-1.0microgkg(-1)min(-1) for 10-20min followed by 0.5microgkg(-1)min(-1) continuous infusion is recommended to produce an effective concentration (5-10ngml(-1)) within 10-20min and to maintain a therapeutic concentration throughout the administration period after cardiopulmonary bypass.

A gravimetric technique for evaluating flow continuity from two infusion devices.

PubMed

Leff, R D; True, W R; Roberts, R J

1987-06-01

A computerized gravimetric technique for examining the flow continuity from infusion devices was developed, and two infusion devices with different mechanisms of pump operation were evaluated to illustrate this technique. A BASIC program that records serial weight measurements and calculates weight change from previous determinations was written for and interfaced with a gravimetric balance and IBM PC. A plot of effused weight (normalized weight change that reflects the difference between desired timed-sample interval and actual time) versus time (desired timed-sample interval) was constructed. The gravimetric technique was evaluated using both a peristaltic-type and a piston-type infusion pump. Intravenous solution (5% dextrose and 0.9% sodium chloride) was effused at 10 mL/hr and collected in a beaker. Weights were measured at 10-second intervals over a two-hour infusion period, and the weights of the effused solution were plotted versus time. Flow continuity differed between the two infusion devices. Actual effused weight decreased to 0.007 g/10 sec during the refill cycle of the piston-type pump; the mean (+/- S.D.) effused weight was 0.029 +/- 0.002 g/10 sec. The desired effusion rate was 0.028 g/10 sec. The peristaltic pump had greater flow continuity, with a mean effusion weight of 0.028 +/- 0.003 g/10 sec. The gravimetric technique described in this report can be used to quantitatively depict the effusion profiles of infusion devices. Further studies are needed to identify the degree of flow continuity that is clinically acceptable for infusion devices.

Continuous IV Crotalidae Polyvalent Immune Fab (Ovine) (FabAV) for selected North American rattlesnake bite patients.

PubMed

Bush, Sean P; Seifert, Steven A; Oakes, Jennifer; Smith, Susan D; Phan, Tammy H; Pearl, Sarah R; Reibling, Ellen T

2013-07-01

In patients bitten by North American rattlesnakes and treated with Crotalidae Polyvalent Immune Fab (Ovine) (FabAV), late hematologic abnormalities-persistent, recurrent, or late, new onset of hypofibrinogenemia, prolonged PT/INR, prolonged PTT, and/or thrombocytopenia beyond 48 h post-envenomation-are common, difficult to manage, and may result in morbidity and mortality are common, difficult to manage, and may result in morbidity and mortality. The optimal management of late hematologic abnormalities, particularly the use of further treatment with antivenom, has not been well defined. The current FabAV treatment regimen is to give antivenom as a bolus dose over a one-hour period. We describe our experience using a continuous intravenous infusion of FabAV for late hematologic effects and/or associated bleeding complications in rattlesnake envenomation. This is a retrospective, observational case series of patients envenomated by North American rattlesnakes at three medical centers managed with a continuous intravenous infusion of FabAV for late hematologic abnormalities and/or associated bleeding complications. Indications, dilution and infusion protocols, and duration of therapy were individualized. Five cases were identified between July 2010 and September 2011. All patients had profound late hematologic abnormalities and/or were associated with bleeding complications. Several patients had received repeat bolus infusions of FabAV, with or without human blood products, with either inadequate or only transient beneficial response. All patients were then managed with a continuous intravenous infusion of FabAV and all appeared to respond to the continuous intravenous infusion of FabAV, titrated to effect, with cessation of progression and, in most cases, improvement in hematologic abnormalities. Rates of infusion varied from 2 to 4 vials per 24 h (mean = 3.1 ± 0.4 vials/day). The termination of FabAV infusion was between day 6 and day 14 from the time of envenomation (mean = 10 ± 3 days), after which hematologic values were normalized or were normalizing in all patients and continued to do so. The use of FabAV as a continuous intravenous infusion, particularly after the acute phase of envenomation has passed, provides a continuous source of circulating antibodies to neutralize venom components reaching circulation from tissue stores and allows natural replenishment of hematologic factors such as platelets and/or fibrinogen. This method is an efficient use of FabAV, avoiding the wasteful excess of a bolus dose, may be more effective, eliminating the potential for destruction of hematologic factors when protective antivenom levels are lost between bolus FabAV doses, and appears to be safe. Further assessments of the stability and sterility of the product during infusion are needed. The need to continue hospitalization is the major drawback, but continued observation and inpatient care may be needed for other indications (e.g. bleeding) in this subset of patients. A continuous intravenous infusion of FabAV between 2 and 4 vials per day, titrated to effect, and continued for 6-14 days post-envenomation appeared to be associated with reversal of late hematologic effects of rattlesnake envenomation and, when combined with indicated human blood products, control of significant bleeding. Continuous intravenous infusion of FabAV may be safer, more efficacious, and more cost-effective than observation without FabAV treatment or as-needed bolus dosing in selected patients with late hematologic abnormalities. Copyright © 2013 Elsevier Ltd. All rights reserved.

Computerized Orders with Standardized Concentrations Decrease Dispensing Errors of Continuous Infusion Medications for Pediatrics

PubMed Central

Sowan, Azizeh K.; Vaidya, Vinay U.; Soeken, Karen L.; Hilmas, Elora

2010-01-01

OBJECTIVES The use of continuous infusion medications with individualized concentrations may increase the risk for errors in pediatric patients. The objective of this study was to evaluate the effect of computerized prescriber order entry (CPOE) for continuous infusions with standardized concentrations on frequency of pharmacy processing errors. In addition, time to process handwritten versus computerized infusion orders was evaluated and user satisfaction with CPOE as compared to handwritten orders was measured. METHODS Using a crossover design, 10 pharmacists in the pediatric satellite within a university teaching hospital were given test scenarios of handwritten and CPOE order sheets and asked to process infusion orders using the pharmacy system in order to generate infusion labels. Participants were given three groups of orders: five correct handwritten orders, four handwritten orders written with deliberate errors, and five correct CPOE orders. Label errors were analyzed and time to complete the task was recorded. RESULTS Using CPOE orders, participants required less processing time per infusion order (2 min, 5 sec ± 58 sec) compared with time per infusion order in the first handwritten order sheet group (3 min, 7 sec ± 1 min, 20 sec) and the second handwritten order sheet group (3 min, 26 sec ± 1 min, 8 sec), (p<0.01). CPOE eliminated all error types except wrong concentration. With CPOE, 4% of infusions processed contained errors, compared with 26% of the first group of handwritten orders and 45% of the second group of handwritten orders (p<0.03). Pharmacists were more satisfied with CPOE orders when compared with the handwritten method (p=0.0001). CONCLUSIONS CPOE orders saved pharmacists' time and greatly improved the safety of processing continuous infusions, although not all errors were eliminated. pharmacists were overwhelmingly satisfied with the CPOE orders PMID:22477811

Intractable Polyuria Mimicking Diabetes Insipidus-Source Traced to Vecuronium Infusion.

PubMed

Haldar, Rudrashish; Samanta, Sukhen; Singla, Ankush

2016-01-01

Continuous infusion of vecuronium is a commonly used technique for patients requiring prolonged neuromuscular blockade for mechanical ventilation. As compared with older neuromuscular blocking agents, it confers the advantages of rapid excretion and intermediate duration of action. Prolongation of neuromuscular blockade and muscle weakness are the known complications of continuous vecuronium infusion. This report attempts to describe polyuria, as a hitherto unknown complication of vecuronium infusion, which can occur due to the mannitol present in commercially available preparation of vecuronium bromide.

Pharmacokinetic-Pharmacodynamic Model for the Effect of l-Arginine on Endothelial Function in Patients with Moderately Severe Falciparum Malaria

PubMed Central

Brussee, Janneke M.; Yeo, Tsin W.; Lampah, Daniel A.; Anstey, Nicholas M.

2015-01-01

Impaired organ perfusion in severe falciparum malaria arises from microvascular sequestration of parasitized cells and endothelial dysfunction. Endothelial dysfunction in malaria is secondary to impaired nitric oxide (NO) bioavailability, in part due to decreased plasma concentrations of l-arginine, the substrate for endothelial cell NO synthase. We quantified the time course of the effects of adjunctive l-arginine treatment on endothelial function in 73 patients with moderately severe falciparum malaria derived from previous studies. Three groups of 10 different patients received 3 g, 6 g, or 12 g of l-arginine as a half-hour infusion. The remaining 43 received saline placebo. A pharmacokinetic-pharmacodynamic (PKPD) model was developed to describe the time course of changes in exhaled NO concentrations and reactive hyperemia-peripheral arterial tonometry (RH-PAT) index values describing endothelial function and then used to explore optimal dosing regimens for l-arginine. A PK model describing arginine concentrations in patients with moderately severe malaria was extended with two pharmacodynamic biomeasures, the intermediary biochemical step (NO production) and endothelial function (RH-PAT index). A linear model described the relationship between arginine concentrations and exhaled NO. NO concentrations were linearly related to RH-PAT index. Simulations of dosing schedules using this PKPD model predicted that the time within therapeutic range would increase with increasing arginine dose. However, simulations demonstrated that regimens of continuous infusion over longer periods would prolong the time within the therapeutic range even more. The optimal dosing regimen for l-arginine is likely to be administration schedule dependent. Further studies are necessary to characterize the effects of such continuous infusions of l-arginine on NO and microvascular reactivity in severe malaria. PMID:26482311

Comparison of continuous subcutaneous and intravenous hydromorphone infusions for management of cancer pain.

PubMed

Moulin, D E; Kreeft, J H; Murray-Parsons, N; Bouquillon, A I

1991-02-23

To compare the safety and efficacy of subcutaneous and intravenous infusion of opioid analgesics, a randomised, double-blind, crossover trial was carried out in inpatients. 15 patients with severe cancer pain received two 48 h infusions of hydromorphone--one subcutaneously and one intravenously in randomly allocated order. The study was made double-blind by the use of two infusion pumps throughout; during the active subcutaneous infusion the intravenous pump delivered saline and vice versa. Serial measurements of pain intensity, pain relief, mood, and sedation by means of visual analogue scales showed no clinically or statistically significant difference between the two infusion routes. Side-effects were slight, and the mean number of morphine injections for breakthrough pain did not differ significantly between the routes (4.8 [SD 4.5] for intravenous vs 5.3 [5.6] for subcutaneous). Plasma hydromorphone concentrations measured at 24 h and 48 h of infusion showed stable steady-state pharmacokinetics; the mean bioavailability from subcutaneous infusion was 78% of that with intravenous infusion. Because of the simplicity, technical advantages, and cost-effectiveness of continuous subcutaneous opioid infusion into the chest wall or trunk, intravenous opioid infusion for the management of severe cancer pain should be abandoned.

A Two-Day Continuous Nicotine Infusion Is Sufficient to Demonstrate Nicotine Withdrawal in Rats as Measured Using Intracranial Self-Stimulation.

PubMed

Muelken, Peter; Schmidt, Clare E; Shelley, David; Tally, Laura; Harris, Andrew C

2015-01-01

Avoidance of the negative affective (emotional) symptoms of nicotine withdrawal (e.g., anhedonia, anxiety) contributes to tobacco addiction. Establishing the minimal nicotine exposure conditions required to demonstrate negative affective withdrawal signs in animals, as well as understanding moderators of these conditions, could inform tobacco addiction-related research, treatment, and policy. The goal of this study was to determine the minimal duration of continuous nicotine infusion required to demonstrate nicotine withdrawal in rats as measured by elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior). Administration of the nicotinic acetylcholine receptor antagonist mecamylamine (3.0 mg/kg, s.c.) on alternate test days throughout the course of a 2-week continuous nicotine infusion (3.2 mg/kg/day via osmotic minipump) elicited elevations in ICSS thresholds beginning on the second day of infusion. Magnitude of antagonist-precipitated withdrawal did not change with further nicotine exposure and mecamylamine injections, and was similar to that observed in a positive control group receiving mecamylamine following a 14-day nicotine infusion. Expression of a significant withdrawal effect was delayed in nicotine-infused rats receiving mecamylamine on all test days rather than on alternate test days. In a separate study, rats exhibited a transient increase in ICSS thresholds following cessation of a 2-day continuous nicotine infusion (3.2 mg/kg/day). Magnitude of this spontaneous withdrawal effect was similar to that observed in rats receiving a 9-day nicotine infusion. Our findings demonstrate that rats exhibit antagonist-precipitated and spontaneous nicotine withdrawal following a 2-day continuous nicotine infusion, at least under the experimental conditions studied here. Magnitude of these effects were similar to those observed in traditional models involving more prolonged nicotine exposure. Further development of these models, including evaluation of more clinically relevant nicotine dosing regimens and other measures of nicotine withdrawal (e.g., anxiety-like behavior, somatic signs), may be useful for understanding the development of the nicotine withdrawal syndrome.

A Two-Day Continuous Nicotine Infusion Is Sufficient to Demonstrate Nicotine Withdrawal in Rats as Measured Using Intracranial Self-Stimulation

PubMed Central

Muelken, Peter; Schmidt, Clare E.; Shelley, David; Tally, Laura; Harris, Andrew C.

2015-01-01

Avoidance of the negative affective (emotional) symptoms of nicotine withdrawal (e.g., anhedonia, anxiety) contributes to tobacco addiction. Establishing the minimal nicotine exposure conditions required to demonstrate negative affective withdrawal signs in animals, as well as understanding moderators of these conditions, could inform tobacco addiction-related research, treatment, and policy. The goal of this study was to determine the minimal duration of continuous nicotine infusion required to demonstrate nicotine withdrawal in rats as measured by elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior). Administration of the nicotinic acetylcholine receptor antagonist mecamylamine (3.0 mg/kg, s.c.) on alternate test days throughout the course of a 2-week continuous nicotine infusion (3.2 mg/kg/day via osmotic minipump) elicited elevations in ICSS thresholds beginning on the second day of infusion. Magnitude of antagonist-precipitated withdrawal did not change with further nicotine exposure and mecamylamine injections, and was similar to that observed in a positive control group receiving mecamylamine following a 14-day nicotine infusion. Expression of a significant withdrawal effect was delayed in nicotine-infused rats receiving mecamylamine on all test days rather than on alternate test days. In a separate study, rats exhibited a transient increase in ICSS thresholds following cessation of a 2-day continuous nicotine infusion (3.2 mg/kg/day). Magnitude of this spontaneous withdrawal effect was similar to that observed in rats receiving a 9-day nicotine infusion. Our findings demonstrate that rats exhibit antagonist-precipitated and spontaneous nicotine withdrawal following a 2-day continuous nicotine infusion, at least under the experimental conditions studied here. Magnitude of these effects were similar to those observed in traditional models involving more prolonged nicotine exposure. Further development of these models, including evaluation of more clinically relevant nicotine dosing regimens and other measures of nicotine withdrawal (e.g., anxiety-like behavior, somatic signs), may be useful for understanding the development of the nicotine withdrawal syndrome. PMID:26658557

Discharge prescribing of enteral opioids after initiation as a weaning strategy from continuous opioid infusions in the Intensive Care Unit.

PubMed

Kram, Bridgette; Weigel, Kylie M; Kuhrt, Michelle; Gilstrap, Daniel L

To evaluate the proportion of patients receiving a hospital discharge prescription for a scheduled enteral opioid following initiation as a weaning strategy from a continuous opioid infusion in the Intensive Care Unit (ICU). Retrospective, observational study. Five adult ICUs at a large, quaternary care academic medical center. Endotracheally intubated, opioid-naive adults receiving a continuous opioid infusion with a concomitant scheduled enteral opioid initiated. Exclusion criteria were receipt of fewer than two enteral opioid doses, documentation of a long-acting opioid as a home medication, the indication for the enteral opioid was not a weaning strategy, death during hospital admission or discharge to hospice. None. The proportion of ICU and hospital survivors who received a discharge prescription for a scheduled enteral opioid, total duration of continuous opioid infusion, duration of continuous opioid infusion after initiation of an enteral opioid therapy, total duration of enteral therapy, ICU and hospital length of stay. Of 62 included patients, 19 patients (30.6 percent) received a new prescription for a scheduled enteral opioid at hospital discharge. The median duration of enteral opioid therapy was longer for patients who received a discharge prescription compared to those who did not (20.09 vs 8.89 days, p = 0.02), though the remaining endpoints were not different. Utilizing scheduled enteral opioids as a weaning strategy from continuous opioid infusions may place patients at risk of ICU-acquired physical dependence on opioids.

[Portable elastomeric infusion system applied to patients with knee prosthesis].

PubMed

Soler, Gemma; Quiles, Olga; Nicolau, Agnes; Faura, Teresa; Moreno, Cristina

2007-03-01

An LV infuser consists of an infusion pump which can administer medicines via various methods: intravenous, epidural, subdural, o subcutaneous. Its usefulness is based on the administration of medicines such as oncological drugs and/or analgesic by means of a continuous infusion.

Ramped-rate vs continuous-rate infusions: An in vitro comparison of convection enhanced delivery protocols.

PubMed

Schomberg, Dominic; Wang, Anyi; Marshall, Hope; Miranpuri, Gurwattan; Sillay, Karl

2013-04-01

Convection enhanced delivery (CED) is a technique using infusion convection currents to deliver therapeutic agents into targeted regions of the brain. Recently, CED is gaining significant acceptance for use in gene therapy of Parkinson's disease (PD) employing direct infusion into the brain. CED offers advantages in that it targets local areas of the brain, bypasses the blood-brain barrier (BBB), minimizes systemic toxicity of the therapeutics, and allows for delivery of larger molecules that diffusion driven methods cannot achieve. Investigating infusion characteristics such as backflow and morphology is important in developing standard and effective protocols in order to successfully deliver treatments into the brain. Optimizing clinical infusion protocols may reduce backflow, improve final infusion cloud morphology, and maximize infusate penetrance into targeted tissue. The purpose of the current study was to compare metrics during ramped-rate and continuous-rate infusions using two different catheters in order to optimize current infusion protocols. Occasionally, the infusate refluxes proximally up the catheter tip, known as backflow, and minimizing this can potentially reduce undesirable effects in the clinical setting. Traditionally, infusions are performed at a constant rate throughout the entire duration, and backflow is minimized only by slow infusion rates, which increases the time required to deliver the desired amount of infusate. In this study, we investigate the effects of ramping and various infusion rates on backflow and infusion cloud morphology. The independent parameters in the study are: ramping, maximum infusion rate, time between rate changes, and increments of rate changes. Backflow was measured using two methods: i) at the point of pressure stabilization within the catheter, and ii) maximum backflow as shown by video data. Infusion cloud morphology was evaluated based on the height-to-width ratio of each infusion cloud at the end of each experiment. Results were tabulated and statistically analyzed to identify any significant differences between protocols. The experimental results show that CED rampedrate infusion protocols result in smaller backflow distances and more spherical cloud morphologies compared to continuous-rate infusion protocols ending at the same maximum infusion rate. Our results also suggest internal-line pressure measurements can approximate the time-point at which backflow ceases. Our findings indicate that ramping CED infusion protocols can potentially minimize backflow and produce more spherical infusion clouds. However, further research is required to determine the strength of this correlation, especially in relation to maximum infusion rates.

Subcutaneous narcotic infusions for cancer pain: treatment outcome and guidelines for use.

PubMed

Moulin, D E; Johnson, N G; Murray-Parsons, N; Geoghegan, M F; Goodwin, V A; Chester, M A

1992-03-15

To provide guidelines for the institution and maintenance of a continuous subcutaneous narcotic infusion program for cancer patients with chronic pain through an analysis of the narcotic requirements and treatment outcomes of patients who underwent such therapy and a comparison of the costs of two commonly used infusion systems. Retrospective study. Tertiary care facilities and patients' homes. Of 481 patients seen in consultation for cancer pain between July 1987 and April 1990, 60 (12%) met the eligibility criteria (i.e., standard medical management had failed, and they had adequate supervision at home). Continuous subcutaneous infusion with hydromorphone hydrochloride or morphine started on an inpatient basis and continued at home whenever possible. Patient selectivity, narcotic dosing requirements, discharge rate, patient preference for analgesic regimen, side effects, complications and cost-effectiveness. The mean initial maintenance infusion dose after dose titration was almost three times higher than the dose required before infusion (hydromorphone or equivalent 6.2 v. 2.1 mg/h). Eighteen patients died, and the remaining 42 were discharged home for a mean of 94.4 (standard deviation 128.3) days (extremes 12 and 741 days). The mean maximum infusion rate was 24.1 mg/h (extremes 0.5 and 180 mg/h). All but one of the patients preferred the infusion system to their previous oral analgesic regimen. Despite major dose escalations nausea and vomiting were well controlled in all cases. Twelve patients (20%) experienced serious systemic toxic effects or complications; six became encephalopathic, which necessitated dose reduction, five had a subcutaneous infection necessitating antibiotic treatment, and one had respiratory depression. The programmable computerized infusion pump was found to be more cost-effective than the disposable infusion device after a break-even point of 8 months. Continuous subcutaneous infusion of opioid drugs with the use of a portable programmable pump is safe and effective in selected patients who have failed to respond to standard medical treatment of their cancer pain. Dose titration may require rapid dose escalation, but this is usually well tolerated. For most communities embarking on such a program a programmable infusion system will be more cost-effective than a disposable system.

Influence of infusion pump operation and flow rate on hemodynamic stability during epinephrine infusion.

PubMed

Klem, S A; Farrington, J M; Leff, R D

1993-08-01

To determine whether variations in the flow rate of epinephrine solutions administered via commonly available infusion pumps lead to significant variations in blood pressure (BP) in vivo. Prospective, randomized, crossover study with factorial design, using infusion pumps with four different operating mechanisms (pulsatile diaphragm, linear piston/syringe, cyclic piston-valve, and linear peristaltic) and three drug delivery rates (1, 5, and 10 mL/hr). Two healthy, mixed-breed dogs (12 to 16 kg). Dogs were made hypotensive with methohexital bolus and continuous infusion. BP was restored to normal with constant-dose epinephrine infusion via two pumps at each rate. Femoral mean arterial pressure (MAP) was recorded every 10 secs. Pump-flow continuity was quantitated in vitro using a digital gravimetric technique. Variations in MAP and flow continuity were expressed by the coefficient of variation; analysis of variance was used for comparisons. The mean coefficients of variations for MAP varied from 3.8 +/- 3.1% (linear piston/syringe) to 6.1 +/- 6.6% (linear peristaltic), and from 3.4 +/- 2.2% (10 mL/hr) to 7.9 +/- 6.6% (1 mL/hr). The coefficients of variation for in vitro flow continuity ranged from 9 +/- 8% (linear piston-syringe) to 250 +/- 162% (pulsatile diaphragm), and from 35 +/- 44% (10 mL/hr) to 138 +/- 196% (1 mL/hr). Both the type of pump and infusion rate significantly (p < .001) influenced variation in drug delivery rate. The 1 mL/hr infusion rate significantly (p < .01) influenced MAP variation. Cyclic fluctuations in MAP of < or = 30 mm Hg were observed using the pulsatile diaphragm pump at 1 mL/hr. Factors inherent in the operating mechanisms of infusion pumps may result in clinically important hemodynamic fluctuations when administering a concentrated short-acting vasoactive medication at slow infusion rates.

Suppression of GH secretion in pituitary gigantism by continuous subcutaneous octreotide infusion in a pubertal boy.

PubMed

Näntö-Salonen, K; Koskinen, P; Sonninen, P; Toppari, J

1999-01-01

We describe a 12-y-old boy with excessive growth hormone and prolactin secretion presumably due to diffuse somatotroph hyperplasia. Until mid-puberty, his growth rate was under reasonable control, with high-dose octreotide injections every 8 h combined with a dopamine agonist. As his growth velocity started to increase, the efficacy of continuous s.c. octreotide infusion on GH secretion was tested. Similar total daily doses (600 microg) of octreotide were administered either by incremental s.c. injections at 8 h intervals, or by continuous s.c. infusion, two-thirds of the amount during night-time to control the presumed high nocturnal growth hormone (GH) peaks of the pubertal growth spurt. An overnight GH profile showed inadequate suppression of GH levels by incremental injections, while continuous s.c. infusion efficiently brought down the GH secretion. Another somatostatin analogue, lanreotide as a single depot injection was not effective. A 6-mo trial on the s.c. infusion regimen significantly reduced growth hormone secretion (as judged by IGF-I and IGFBP3 concentrations), and normalized growth velocity overcoming the pubertal growth spurt. It also caused a decrease in the pituitary size in magnetic resonance images. We conclude that the efficacy of octreotide infusion in suppressing GH secretion is superior to incremental injections with the same dose.

Pharmacodynamic Evaluation of Extending the Administration Time of Meropenem using a Monte Carlo Simulation

PubMed Central

Lomaestro, Ben M.; Drusano, G. L.

2005-01-01

A Monte Carlo simulation demonstrated that 1 g of meropenem (MEM) every 8 h (q8h) (3-h infusion) has a higher target attainment rate against Pseudomonas aeruginosa than either 500 mg of MEM q8h (3-h infusion) or 0.5 g of imipenem-cilastatin (I-C) q6h (1-h infusion). For other pathogens, 500 mg of MEM q8h was equivalent or superior to I-C. PMID:15616337

Population pharmacokinetics of the piperacillin component of piperacillin/tazobactam in pediatric oncology patients with fever and neutropenia.

PubMed

Cies, Jeffrey J; Jain, Jaimi; Kuti, Joseph L

2015-03-01

To describe the population pharmacokinetics of the piperacillin component of piperacillin/tazobactam. This pharmacokinetic study included 21 pediatric (age 3-10 years) patients receiving piperacillin/tazobactam to treat fever with neutropenia. Each patient contributed 1-3 blood samples for piperacillin concentration determination. Population pharmacokinetic analyses were conducted using Pmetrics software. A 5,000 patient Monte Carlo simulation was performed to determine the probability of target attainment (PTA) for multiple dosing regimens, using 50% of free drug time above the minimum inhibitory concentration (MIC) as the primary pharmacodynamic threshold. Mean ± SD body weight was 28.5 ± 9.7 kg. Piperacillin concentration data best fit a two-compartment model with linear clearance, using total body weight as a covariate for clearance (CLθ ) and volume of the central compartment (Vcθ ). Population estimates for CLθ , Vcθ , and intercompartment transfer constants were 0.204 ± 0.076 L/h/kg, 0.199 ± 0.107 L/kg, 0.897 ± 1.050 h(-1) , and 1.427 ± 1.609 h(-1) , respectively. R(2) , bias, and precision for the Bayesian fit were 0.998, -0.032, and 2.2 µg/ml, respectively. At the MIC breakpoint of 16 µg/ml for Pseudomonas aeruginosa, PTAs for 50 mg/kg q4h as a 0.5 hr infusion was 93.9%; for 100 mg/kg q8h as 0.5 and 4 hr infusion: 64.6% and 100%; for 100 mg/kg q6h as 0.5 and 3 hr infusion: 86.5% and 100%; and for 400 mg/kg continuous infusion: 100%, respectively. In children with fever and neutropenia, piperacillin/tazobactam dosing regimens that are administered every 4 hr or that employ prolonged or continuous infusions should be considered to optimize pharmacodynamic exposure. © 2014 Wiley Periodicals, Inc.

Continuous delivery of ropinirole reverses motor deficits without dyskinesia induction in MPTP-treated common marmosets.

PubMed

Stockwell, K A; Virley, D J; Perren, M; Iravani, M M; Jackson, M J; Rose, S; Jenner, P

2008-05-01

L-DOPA treatment of Parkinson's disease induces a high incidence of motor complications, notably dyskinesia. Longer acting dopamine agonists, e.g. ropinirole, are thought to produce more continuous dopaminergic stimulation and less severe dyskinesia. However, standard oral administration of dopamine agonists does not result in constant plasma drug levels, therefore, more continuous drug delivery may result in both prolonged reversal of motor deficits and reduced levels of dyskinesia. Therefore, we compared the effects of repeated oral administration of ropinirole to constant subcutaneous infusion in MPTP-treated common marmosets. Animals received oral administration (0.4 mg/kg, BID) or continuous infusion of ropinirole (0.8 mg/kg/day) via osmotic minipumps for 14 days (Phase I). The treatments were then switched and continued for a further 14 days (Phase II). In Phase I, locomotor activity was similar between treatment groups but reversal of motor disability was more pronounced in animals receiving continuous infusion. Dyskinesia intensity was low in both groups however there was a trend suggestive of less marked dyskinesia in those animals receiving continuous infusion. In Phase II, increased locomotor activity was maintained but animals switched from oral to continuous treatment showing an initial period of enhanced locomotor activity. The reversal of motor disability was maintained in both groups, however, motor disability tended towards greater improvement following continuous infusion. Importantly, dyskinesia remained low in both groups suggesting that constant delivery of ropinirole neither leads to priming nor expression of dyskinesia. These results suggest that a once-daily controlled-release formulation may provide improvements over existing benefits with standard oral ropinirole in Parkinson's disease patients.

Continuous intra-articular infusion anesthesia for pain control after total knee arthroplasty: study protocol for a randomized controlled trial.

PubMed

Guo, Da; Cao, Xue-Wei; Liu, Jin-Wen; Ouyang, Wen-Wei; Pan, Jian-Ke; Liu, Jun

2014-06-23

Postoperative pain control after total knee arthroplasty (TKA) remains a great challenge. The management of pain in the immediate postoperative period is one of the most critical aspects to allow speedier rehabilitation and reduce the risk of postoperative complications. Recently, periarticular infiltration anesthesia has become popular, but the outcome is controversial. Some studies have shown transient effects, "rebound pain", or no effectiveness in pain control. Continuous intra-articular infusion technique has been introduced to improve these transient effects, but more clinical studies are needed. Furthermore, the potential risk of early periprosthetic joint infection is causing concerning. We plan to compare continuous intra-articular infusion anesthesia with epidural infusion anesthesia after TKA to assess the effectiveness of this technique in reducing pain, in improving postoperative function, and to look at the evidence for risk of early infection. This trial is a randomized, controlled study. Patients (n = 214) will be randomized into two groups: to receive continuous intra-articular infusion anesthesia (group C); and epidural infusion anesthesia (group E). For the first 3 postoperative days, pain at rest, active range of motion (A-ROM), rescue analgesia and side effects will be recorded. At 3-month and 6-month follow-up, A-ROM, C-reactive protein, erythrocyte sedimentation rate, and synovial fluid cell count and culture will be analyzed. The results from this study will provide clinical evidence on the efficacy of a continuous intra-articular infusion technique in reducing pain, postoperative functional improvement and safety. It will be the first randomized controlled trial to investigate infection risk with local anesthesia after TKA. ClinicalTrials.gov identifier: ChiCTR-TRC-13003999.

Effect of 2',3'-didehydro-3'-deoxythymidine in an in vitro hollow-fiber pharmacodynamic model system correlates with results of dose-ranging clinical studies.

PubMed Central

Bilello, J A; Bauer, G; Dudley, M N; Cole, G A; Drusano, G L

1994-01-01

We sought to validate an in vitro system which could predict the minimal effect dose of antiretroviral agents. Mixtures of uninfected CEM cells and CEM cells chronically infected with human immunodeficiency virus (HIV) type 1 MN were exposed to 2',3'-didehydro-3'-deoxythymidine (D4T) in vitro in a hollow-fiber model which simulates the plasma concentration-time profile of D4T in patients. Drug concentration was adjusted to simulate continuous intravenous infusion, or an intravenous bolus administered twice daily. The effect of the dosing regimen was measured with viral infectivity, p24 antigen, and reverse transcriptase or PCR for unintegrated HIV DNA. Dose deescalation studies on a twice-daily dosing schedule predicted a minimum effect dose of 0.5 mg/kg of body weight per day which correlated with the results of a clinical trial. Antiviral effect was demonstrated to be independent of schedule for every 12-h dosing versus continuous infusion. Finally, at or near the minimal effect dose, efficacy appeared to depend on the viral load. The ability of this in vitro pharmacodynamic model to assess the response of HIV-infected cells to different doses and schedules of antiviral agents may be useful in the design of optimal dosing regimens for clinical trials but requires validation with other types of antiretroviral agents. PMID:8092842

The Pringle maneuver reduces the infusion rate of rocuronium required to maintain surgical muscle relaxation during hepatectomy.

PubMed

Kajiura, Akira; Nagata, Osamu; Sanui, Masamitsu

2018-04-27

We investigated the continuous infusion rates of rocuronium necessary to obtain the surgical muscle relaxation before, during, and after the Pringle maneuver on patients who underwent hepatectomy. Fifteen patients were induced by total intravenous anesthesia with propofol. After obtaining the calibration of acceleromyography, the patient was intubated with rocuronium 0.6 mg/kg. Fifteen minutes after initial rocuronium injection, the continuous infusion was started at 7.5 µg/kg/min. The infusion rate was adjusted every 15 min so that the first twitch height (% T1) might become from 3 to 10% of control. The infusion rates at the time when the state of surgical muscle relaxation was achieved for more than 15 min were recorded before, during and after the Pringle maneuver. The 25% recovery time was measured after discontinuing the continuous infusion. The infusion rate of rocuronium before, during, and after the Pringle maneuver was 7.2 ± 1.8, 4.2 ± 1.4, and 4.7 ± 1.5 µg/kg/min (mean ± SD), respectively. The rocuronium infusion rate during the Pringle maneuver was decreased about 40% compared to that before this maneuver, and that after completion of the Pringle maneuver was not recovered to that before the Pringle maneuver. The 25% recovery time was 20 ± 7 min. In case of continuous administration of rocuronium during surgery performing the Pringle maneuver, it was considered necessary to regulate the administration of rocuronium using muscle relaxant monitoring in order to deal with the decrease in muscle relaxant requirement by the Pringle maneuver.

Radiofrequency Thermal Ablation: Increase in Lesion Diameter with Continuous Acetic Acid Infusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lubienski, Andreas; Duex, Markus; Lubienski, Katrin

Purpose. To evaluate the influence of continuous infusion of acetic acid 50% during radiofrequency ablation (RFA) on the size of the thermal lesion produced. Methods. Radiofrequency (RF) was applied to excised bovine liver by using an expandable needle electrode with 10 retractable tines (LeVeen Needle Electrode, RadioTherapeutics, Sunnyvale, CA) connected to a commercially available RF generator (RF 2000, RadioTherapeutics, Sunnyvale, CA). Experiments were performed using three different treatment modalities: RF only (n = 15), RF with continuous saline 0.9% infusion (n = 15), and RF with continuous acetic acid 50% infusion (n = 15). RF duration, power output, tissue impedance,more » and time to a rapid rise in impedance were recorded. The ablated lesions were evaluated both macroscopically and histologically. Results. The ablated lesions appeared as spherical or ellipsoid, well-demarcated pale areas with a surrounding brown rim with both RF only and RF plus saline 0.9% infusion. In contrast, thermolesions generated with RF in combination with acetic acid 50% infusion were irregular in shape and the central portion was jelly-like. Mean diameter of the coagulation necrosis was 22.3 {+-} 2.1 mm (RF only), 29.2 {+-} 4.8 mm (RF + saline 0.9%) and 30.7 {+-} 5.7 mm (RF + acetic acid 50%), with a significant increase in the RF plus saline 0.9% and RF plus acetic acid 50% groups compared with RF alone. Time to a rapid rise in impedance was significantly prolonged in the RF plus saline 0.9% and RF plus acetic acid 50% groups compared with RF alone. Conclusions. A combination of RF plus acetic acid 50% infusion is able to generate larger thermolesions than RF only or RF combined with saline 0.9% infusion.« less

Continuous versus bolus intermittent loop diuretic infusion in acutely decompensated heart failure: a prospective randomized trial

PubMed Central

2014-01-01

Introduction Intravenous loop diuretics are a cornerstone of therapy in acutely decompensated heart failure (ADHF). We sought to determine if there are any differences in clinical outcomes between intravenous bolus and continuous infusion of loop diuretics. Methods Subjects with ADHF within 12 hours of hospital admission were randomly assigned to continuous infusion or twice daily bolus therapy with furosemide. There were three co-primary endpoints assessed from admission to discharge: the mean paired changes in serum creatinine, estimated glomerular filtration rate (eGFR), and reduction in B-type natriuretic peptide (BNP). Secondary endpoints included the rate of acute kidney injury (AKI), change in body weight and six months follow-up evaluation after discharge. Results A total of 43 received a continuous infusion and 39 were assigned to bolus treatment. At discharge, the mean change in serum creatinine was higher (+0.8 ± 0.4 versus -0.8 ± 0.3 mg/dl P <0.01), and eGFR was lower (-9 ± 7 versus +5 ± 6 ml/min/1.73 m2P <0.05) in the continuous arm. There was no significant difference in the degree of weight loss (-4.1 ± 1.9 versus -3.5 ± 2.4 kg P = 0.23). The continuous infusion arm had a greater reduction in BNP over the hospital course, (-576 ± 655 versus -181 ± 527 pg/ml P = 0.02). The rates of AKI were comparable (22% and 15% P = 0.3) between the two groups. There was more frequent use of hypertonic saline solutions for hyponatremia (33% versus 18% P <0.01), intravenous dopamine infusions (35% versus 23% P = 0.02), and the hospital length of stay was longer in the continuous infusion group (14. 3 ± 5 versus 11.5 ± 4 days, P <0.03). At 6 months there were higher rates of re-admission or death in the continuous infusion group, 58% versus 23%, (P = 0.001) and this mode of treatment independently associated with this outcome after adjusting for baseline and intermediate variables (adjusted hazard ratio = 2.57, 95% confidence interval, 1.01 to 6.58 P = 0.04). Conclusions In the setting of ADHF, continuous infusion of loop diuretics resulted in greater reductions in BNP from admission to discharge. However, this appeared to occur at the consequence of worsened renal filtration function, use of additional treatment, and higher rates of rehospitalization or death at six months. Trial registration ClinicalTrials.gov NCT01441245. Registered 23 September 2011. PMID:24974232

Continuous intravenous morphine infusion for postoperative analgesia following posterior spinal fusion for idiopathic scoliosis.

PubMed

Poe-Kochert, Connie; Tripi, Paul A; Potzman, Jennifer; Son-Hing, Jochen P; Thompson, George H

2010-04-01

A retrospective study of postoperative pain management. Evaluate the efficacy and safety of continuous intravenous morphine infusion for postoperative pain management in patients with idiopathic scoliosis (IS) undergoing posterior spinal fusion (PSF) and segmental spinal instrumentation (SSI). Postoperative pain is a common problem following surgery for IS. There are no published reports regarding the use of a continuous intravenous morphine infusion for this patient population. We retrospectively reviewed data regarding 339 consecutive patients with IS who underwent PSF and SSI between 1992 and 2006. All patients received intrathecal morphine after the induction of general anesthesia. Following surgery, preordered morphine infusion (0.01 mg/kg/h) was started at first reported pain. The infusion rate was titrated based on vital signs, visual analog scale (VAS) pain scores (0-10), and clinical status. It was continued until patients were able to take oral analgesics. We reviewed intrathecal morphine dosage, VAS pain scores through the third postoperative day, interval to start of morphine infusion, total morphine requirements in the first 48 hours, and any adverse reactions (nausea/vomiting, pruritus, respiratory depression, and pediatric intensive care unit admission). Mean intrathecal morphine dose was 15.5 +/- 3.9 microg/kg and mean interval to start of the intravenous morphine infusion was 17.5 +/- 5 hours. Mean VAS pain scores were 3.1, 4.5, 4.5, and 4.6 at 12 hours, 1, 2, and 3 days after surgery, respectively.The total mean morphine dose in the first 48 hours postoperatively was 0.03 +/- 0.01 mg/kg/h. Total morphine received was 1.44 +/- 0.5 mg/kg. Nausea/vomiting and pruritus, related to the morphine infusion occurred in 45 patients (13.3%) and 14 patients (4.1%), respectively. No patients had respiratory depression or required Pediatric Intensive Care Unit admission. A low frequency of adverse events and a mean postoperative VAS pain score of 5 or less demonstrate that a continuous postoperative morphine infusion is a safe and effective method of pain management in patients with IS following PSF and SSI.

Effects of flow rate on the migration of different plasticizers from PVC infusion medical devices

PubMed Central

Eljezi, Teuta; Clauson, Hélène; Lambert, Céline; Bouattour, Yassine; Chennell, Philip; Pereira, Bruno; Sautou, Valérie

2018-01-01

Infusion medical devices (MDs) used in hospitals are often made of plasticized polyvinylchloride (PVC). These plasticizers may leach out into infused solutions during clinical practice, especially during risk-situations, e.g multiple infusions in Intensive Care Units and thus may enter into contact with the patients. The migrability of the plasticizers is dependent of several clinical parameters such as temperature, contact time, nature of the simulant, etc… However, no data is available about the influence of the flow rate at which drug solutions are administrated. In this study, we evaluated the impact of different flow rates on the release of the different plasticizers during an infusion procedure in order to assess if they could expose the patients to more toxic amounts of plasticizers. Migration assays with different PVC infusion sets and extension lines were performed with different flow rates that are used in clinical practice during 1h, 2h, 4h, 8h and 24h, using a lipophilic drug simulant. From a clinical point of view, the results showed that, regardless of the plasticizer, the faster the flow rate, the higher the infused volume and the higher the quantities of plasticizers released, both from infusion sets and extension lines, leading to higher patient exposure. However, physically, there was no significant difference of the migration kinetics linked to the flow rate for a same medical device, reflecting complex interactions between the PVC matrix and the simulant. The migration was especially dependent on the nature and the composition of the medical device. PMID:29474357

Evaluation of adverse events noted in children receiving continuous infusions of dexmedetomidine in the intensive care unit.

PubMed

Honey, Brooke L; Harrison, Donald L; Gormley, Andrew K; Johnson, Peter N

2010-01-01

Dexmedetomidine is an α(2)-adrenergic receptor agonist with sedative and analgesic effects in mechanically ventilated adults and children. Safety and efficacy data are limited in children. The purpose of this study is to retrospectively identify the incidence and types of adverse events noted in children receiving continuous infusions of dexmedetomidine and evaluate potential risk factors for adverse events. Between July 1, 2006, and July 31, 2007, data were collected on all children (< 18 years) who received continuous infusions of dexmedetomidine. Data collection included demographics, dexmedetomidine regimen, and type/number of adverse events. The primary endpoint was the total number of adverse events noted, including: transient hypertension, hypotension, neurological manifestations, apnea, and bradycardia. Secondary endpoints included categorization of each type of adverse event and an assessment of risk factors. A logistic regression model was used to assess the relationship of adverse events with independent variables including length of ICU stay, cumulative dose, peak infusion rate, duration of therapy, PRISM III score, and bolus dose. Thirty-six patients received dexmedetomidine representing 41 infusions. The median age was 16 months (range, 0.1-204 months) and median PRISM III score was 2 (range, 0-18). Eighteen (43.9%) patients received a bolus dose of dexmedetomidine. The median cumulative dose (mcg/kg) and peak dose (mcg/kg/hr) were 8.5 (range, 2.2-193.7) and 0.5 (range, 0.2-0.7), respectively. Dexmedetomidine was continued for a median of 20 (range, 3-263) hours. Six (14.6%) patients were slowly tapered off the continuous infusions. Twenty-one adverse events were noted in 17 patients, including 4 neurologic manifestations. Fourteen patients required interventions for adverse events. ICU length of stay was the only independent risk factor (p=0.036) for development of adverse events. Several potential adverse events were noted with dexmedetomidine continuous infusions including possible neurological manifestations. Further studies are needed looking at adverse events associated with dexmedetomidine use in the pediatric population.

Contribution of propionate to glucose synthesis in sheep

PubMed Central

Leng, R. A.; Steel, J. W.; Luick, J. R.

1967-01-01

1. The production rate of propionate in the rumen and the entry rate of glucose into the body pool of glucose in sheep were measured by isotope-dilution methods. Propionate production rates were measured by using a continuous infusion of specifically labelled [14C]propionate. Glucose entry rates were estimated by using either a primed infusion or a continuous infusion of [U-14C]glucose. 2. The specific radioactivity of plasma glucose was constant between 4 and 9hr. after the commencement of intravenous infusion of [U-14C]glucose and between 1 and 3hr. when a primed infusion was used. 3. Infusion of [14C]propionate intraruminally resulted in a fairly constant specific radioactivity of rumen propionate between about 4 and 9hr. and of plasma glucose between 6 and 9hr. after the commencement of the infusion. Comparison of the mean specific radioactivities of glucose and propionate during these periods allowed estimates to be made of the contribution of propionate to glucose synthesis. 4. Comparisons of the specific radioactivities of plasma glucose and rumen propionate during intraruminal infusions of one of [1-14C]-, [2-14C]-, [3-14C]- and [U-14C]-propionate indicated considerable exchange of C-1 of propionate on conversion into glucose. The incorporation of C-2 and C-3 of propionate into glucose and lactate indicated that 54% of both the glucose and lactate synthesized arose from propionate carbon. 5. No differences were found for glucose entry rates measured either by a primed infusion or by a continuous infusion. The mean entry rate (±s.e.m.) of glucose estimated by using a continuous infusion into sheep was 0·33±0·03 (4) m-mole/min. and by using a primed infusion was 0·32±0·01 (4) m-mole/min. The mean propionate production rate was 1·24±0·03 (8) m-moles/min. The conversion of propionate into glucose was 0·36 m-mole/min., indicating that 32% of the propionate produced in the rumen is used for glucose synthesis. 6. It was indicated that a considerable amount of the propionate converted into glucose was first converted into lactate. PMID:4860545

Continuous DC-CIK infusions restore CD8+ cellular immunity, physical activity and improve clinical efficacy in advanced cancer patients unresponsive to conventional treatments.

PubMed

Zhao, Yan-Jie; Jiang, Ni; Song, Qing-Kun; Wu, Jiang-Ping; Song, Yu-Guang; Zhang, Hong-Mei; Chen, Feng; Zhou, Lei; Wang, Xiao-Li; Zhou, Xin-Na; Yang, Hua-Bing; Ren, Jun; Lyerly, Herbert Kim

2015-01-01

There are few choices for treatment of advanced cancer patients who do not respond to or tolerate conventional anti-cancer treatments. Therefore this study aimed to deploy the benefits and clinical efficacy of continuous dendritic cell-cytokine induced killer cell infusions in such patients. A total of 381 infusions (from 67 advanced cases recruited) were included in this study. All patients underwent peripheral blood mononuclear cell apheresis for the following cellular therapy and dendritic cells-cytokine induced killer cells were expanded in vitro. Peripheral blood T lymphocyte subsets were quantified through flow cytometry to address the cellular immunity status. Clinical efficacy and physical activities were evaluated by RECIST criteria and Eastern Cooperative Oncology Group scores respectively. Logistic regression model was used to estimate the association between cellular infusions and clinical benefits. An average of 5.7±2.94x10(9) induced cells were infused each time and patients were exposed to 6 infusions. Cellular immunity was improved in that cytotoxic CD8+CD28+T lymphocytes were increased by 74% and suppressive CD8+CD28-T lymphocytes were elevated by 16% (p<0.05). Continuous infusion of dendritic cells-cytokine induced killer cells was associated with improvement of both patient status and cellular immunity. A median of six infusions were capable of reducing risk of progression by 70% (95%CI 0.10-0.91). Every elevation of one ECOG score corresponded to a 3.90-fold higher progression risk (p<0.05) and 1% increase of CD8+CD28- T cell proportion reflecting a 5% higher risk of progression (p<0.05). In advanced cancer patients, continuous dendritic cell-cytokine induced killer cell infusions are capable of recovering cellular immunity, improving patient status and quality of life in those who are unresponsive to conventional cancer treatment.

A continuous [15O]H2O production and infusion system for PET imaging

NASA Astrophysics Data System (ADS)

Sajjad, Munawwar; Liow, Jeih-San

1999-06-01

A system for continuous production and infusion of [15O]H2O has been designed for PET cerebral blood flow studies. The injection system consists of a four-port-two-position valve, two Horizon Nxt infusion pumps, and a sterile 50 ml vial. The variation of the production of [15O]H2O was <1%. The variation of activity delivered measured by scanner counts during the steady state period was <2%.

Continuous Regional Arterial Infusion Therapy for Acute Necrotizing Pancreatitis Due to Mycoplasma pneumoniae Infection in a Child

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakagawa, Motoo, E-mail: lmloltlolol@gmail.com; Ogino, Hiroyuki; Shimohira, Masashi

2009-05-15

A case of acute necrotizing pancreatitis due to Mycoplasma pneumoniae infection was treated in an 8-year-old girl. She experienced acute pancreatitis during treatment for M. pneumoniae. Contrast-enhanced computed tomographic scan revealed necrotizing pancreatitis. The computed tomographic severity index was 8 points (grade E). A protease inhibitor, ulinastatin, was provided via intravenous infusion but was ineffective. Continuous regional arterial infusion therapy was provided with gabexate mesilate (FOY-007, a protease inhibitor) and meropenem trihydrate, and the pancreatitis improved. This case suggests that infusion therapy is safe and useful in treating necrotizing pancreatitis in children.

The comparison of the diuretic and natriuretic efficacy of continuous and bolus intravenous furosemide in patients with chronic kidney disease.

PubMed

Sanjay, Srinivas; Annigeri, Rajeev A; Seshadri, Rajagopalan; Rao, Budithi Subba; Prakash, Kowdle C; Mani, Muthu Krishna

2008-06-01

To compare natriuretic, kaliuretic, diuretic and free water clearance efficacy of continuous versus bolus intravenous furosemide administration in patients with chronic renal insufficiency. In a prospective randomized cross-over trial, 42 patients of chronic renal insufficiency were randomized to receive the same dose of intravenous furosemide as bolus and continuous infusion. The effects of bolus and intravenous administration of furosemide on the volume of urine, sodium and potassium excretion were assessed. Mean age was 53.6 +/- 14 years and 23 (55%) were male. The mean modification of diet in renal disease glomerular filtration rate was 20.5 +/- 17 mL/min per 1.73 m(2). The urinary excretion of sodium in intravenous bolus and infusion was 98.1 +/- 78 and 114.4 +/- 100 mmol, respectively (P = 0.001). Total urinary volume following bolus and infusion of furosemide was 1064 +/- 627 and 1170 +/- 764 mL, respectively (0.001). The excretion of potassium was similar in bolus (15.8 +/- 16.6) and infusion (14.3 +/- 9) administration (P = 0.11). The fractional excretion of sodium was higher following infusion (16.63 +/- 16.1) than bolus administration (12.87 +/- 9) of furosemide (P = 0.016). Continuous intravenous infusion of furosemide has significantly better natriuretic and diuretic effect than bolus administration of the same dose of the drug in patients with advanced chronic renal insufficiency.

Baseline albumin is associated with worsening renal function in patients with acute decompensated heart failure receiving continuous infusion loop diuretics.

PubMed

Clarke, Megan M; Dorsch, Michael P; Kim, Susie; Aaronson, Keith D; Koelling, Todd M; Bleske, Barry E

2013-06-01

To identify baseline predictors of worsening renal function (WRF) in an acute decompensated heart failure (ADHF) patient population receiving continuous infusion loop diuretics. Retrospective observational analysis. Academic tertiary medical center. A total of 177 patients with ADHF receiving continuous infusion loop diuretics from January 2006 through June 2009. The mean patient age was 61 years, 63% were male, ~45% were classified as New York Heart Association functional class III, and the median length of loop diuretic infusion was 4 days. Forty-eight patients (27%) developed WRF, and 34 patients (19%) died during hospitalization. Cox regression time-to-event analysis was used to determine the time to WRF based on different demographic and clinical variables. Baseline serum albumin 3 g/dl or less was the only significant predictor of WRF (hazard ratio [HR] 2.87, 95% confidence interval [CI] 1.60-5.16, p=0.0004), which remained significant despite adjustments for other covariates. Serum albumin 3 g/dl or less is a practical baseline characteristic associated with the development of WRF in patients with ADHF receiving continuous infusion loop diuretics. © 2013 Pharmacotherapy Publications, Inc.

A case report of dexmedetomidine used to treat intractable pain and delirium in a tertiary palliative care unit.

PubMed

Hilliard, Neil; Brown, Stuart; Mitchinson, Steve

2015-03-01

This case report describes an end-stage cancer patient with intractable neuropathic pain and delirium who was successfully managed during the last 3 weeks of her life with a continuous subcutaneous infusion of dexmedetomidine. A 55-year-old woman with locally advanced cervical cancer and uncontrolled pelvic pain was admitted to a tertiary palliative care unit for pain management. As her disease progressed, the patient's pelvic pain intensified despite treatment with methadone, gabapentin, ketamine, and hydromorphone administered by continuous subcutaneous infusion plus frequent breakthrough doses of hydromorphone and sufentanil. A continuous subcutaneous infusion of dexmedetomidine was started and titrated to achieve pain relief. The patient's pain and delirium cleared. The treatment was successful in fulfilling the patient's goal of care: not to be deeply and continuously sedated, but to be rousable and of clear mind while still having good pain control. Dexmedetomidine is a potentially useful medication for the targeted treatment of intractable pain and delirium in the tertiary palliative care environment. Future research is required to compare dexmedetomidine infusion to standard treatment with midazolam infusion for treatment of intractable symptoms in the palliative care environment. © The Author(s) 2014.

Ultrasound-guided continuous interscalene block: the influence of local anesthetic background delivery method on postoperative analgesia after shoulder surgery: a randomized trial.

PubMed

Hamdani, Mehdi; Chassot, Olivier; Fournier, Roxane

2014-01-01

Automated bolus delivery has recently been shown to reduce local anesthetic consumption and improve analgesia, compared with continuous infusion, in continuous sciatic and epidural block. However, there are few data on the influence of local anesthetic delivery method on local anesthetic consumption following interscalene blockade. This randomized, double-blind trial was designed to determine whether hourly automated perineural boluses (4 mL) of local anesthesia delivered with patient-controlled pro re nata (PRN, on demand) boluses would result in a reduction in total local anesthesia consumption during continuous interscalene blockade after shoulder surgery compared with continuous perineural infusion (4 mL/h) plus patient-controlled PRN boluses. One hundred one patients undergoing major shoulder surgery under general anesthesia with ultrasound-guided continuous interscalene block were randomly assigned to receive 0.2% ropivacaine via interscalene end-hole catheter either by continuous infusion 4 mL/h (n = 50) or as automated bolus 4 mL/h (n = 51). Both delivery methods were combined with 5 mL PRN boluses of 0.2% ropivacaine with a lockout time of 30 minutes. Postoperative number of PRN boluses, 24- and 48-hour local anesthetic consumption, pain scores, rescue analgesia (morphine), and adverse events were recorded. There were no significant differences in either the number of PRN ropivacaine boluses or total 48 hour local anesthetic consumption between the groups (18.5 [11-25.2] PRN boluses in the continuous infusion group vs 17 [8.5-29] PRN boluses in the automated bolus group). Postoperative pain was similar in both groups; on day 2, the median average pain score was 4 (2-6) in the continuous infusion group versus 3 (2-5) in the automated bolus group (P = 0.54). Nor were any statistically significant intergroup differences observed with respect to morphine rescue, incidence of adverse events, or patient satisfaction. In continuous interscalene blockade under ultrasound guidance after shoulder surgery, automated boluses of local anesthetic combined with PRN boluses did not provide any reduction in local anesthetic consumption or rescue analgesia, compared with continuous infusion combined with PRN boluses.

Rotator cuff healing after continuous subacromial bupivacaine infusion: an in vivo rabbit study

PubMed Central

FRIEL, NICOLE A.; WANG, VINCENT M.; SLABAUGH, MARK A.; WANG, FANCHIA; CHUBINSKAYA, SUSAN; COLE, BRIAN J.

2013-01-01

Background The objective of this study was to evaluate the effects of continuous subacromial bupivacaine infusion on supraspinatus muscle and rotator cuff tendon healing via gross, biomechanical, and histologic analyses. Methods Thirty-three New Zealand White rabbits underwent unilateral supraspinatus transection and rotator cuff repair (RCR). Rabbits were assigned to 1 of 3 groups: (1)RCR only, (2)RCR with continuous saline infusion for 48 hours, or (3)RCR with continuous 0.25% bupivacaine with epinephrine (1:200,000) infusion for 48 hours. Rabbits were sacrificed at either 2 (for histologic assessment) or 8 weeks post-operatively (for biomechanical and histologic assessment). Results Tensile testing showed significantly higher load to failure in intact tendons compared to repaired tendons (p<0.01); however, no statistical differences were detected among RCR only, RCR Saline, and RCR Bupivacaine groups. Histologically, the enthesis of repaired tendons showed increased cellularity and disorganized collagen fibers compared to intact tendons, with no differences between treatment groups. Muscle histology demonstrated scattered degenerative muscle fibers at 2 weeks in both RCR Saline and RCR Bupivacaine, but no degeneration was noted at 8 weeks. Conclusions The healing supraspinatus tendons exposed to bupivacaine infusion showed similar histologic and biomechanical characteristics compared to untreated and saline infused RCR groups. Muscle histology showed fiber damage at 2 weeks for both the saline and bupivacaine treated groups, with no apparent disruption at 8 weeks, suggesting a recovery process. Therefore, subacromial bupivacaine infusion in this rabbit rotator cuff model does not appear to impair muscle or tendon following acute injury and repair. Level Of Evidence Basic science study PMID:22818894

A Contemporary Simulation Infused in the Business Communication Curriculum: A Case Study

ERIC Educational Resources Information Center

Drury-Grogan, Meghann L.; Russ, Travis L.

2013-01-01

This research examines students' reactions to a contemporary simulation infused in the business communication curriculum. Results show that students indicated the experience helped them learn how to work better as a team, how to maintain composure, how the business world works, and how to improve their communication. Students also verified the…

Local infiltration analgesia followed by continuous infusion of local anesthetic solution for total hip arthroplasty: a prospective, randomized, double-blind, placebo-controlled study.

PubMed

Solovyova, Olga; Lewis, Courtland G; Abrams, Jonathan H; Grady-Benson, John; Joyce, Michael E; Schutzer, Steven F; Arumugam, Sivasenthil; Caminiti, Stephanie; Sinha, Sanjay K

2013-11-06

We studied the efficacy of local infiltration analgesia in surgical wounds with 0.2% ropivacaine (50 mL), ketorolac (15 mg), and adrenaline (0.5 mg) compared with that of local infiltration analgesia combined with continuous infusion of 0.2% ropivacaine as a method of pain control after total hip arthroplasty. We hypothesized that as a component of multimodal analgesia, local infiltration analgesia followed by continuous infusion of ropivacaine would result in reduced postoperative opioid consumption and lower pain scores compared with infiltration alone, and that both of these techniques would be superior to placebo. In this prospective, double-blind, placebo-controlled study, 105 patients were randomized into three groups: Group I, in which patients received infiltration with ropivacaine, ketorolac, and adrenaline followed by continuous infusion of 0.2% ropivacaine at 5 mL/hr; Group II, in which patients received infiltration with ropivacaine, ketorolac, and adrenaline followed by continuous infusion of saline solution at 5 mL/hr; and Group III, in which patients received infiltration with saline solution followed by continuous infusion of saline solution at 5 mL/hr.All patients received celecoxib, pregabalin, and acetaminophen perioperatively and patient-controlled analgesia; surgery was performed under general anesthesia. Before wound closure, the tissues and periarticular space were infiltrated with ropivacaine, ketorolac, and adrenaline or saline solution and a fenestrated catheter was placed. The catheter was attached to a pump prefilled with either 0.2% ropivacaine or saline solution set to infuse at 5 mL/hr.The primary outcome measure was postoperative opioid consumption and the secondary outcome measures were pain scores, adverse side effects, and patient satisfaction. There were no differences between groups in the administration of opioids in the operating room, in the recovery room, or on the surgical floor. The pain scores on recovery room admission and discharge and the floor were low and similar between groups. There were no differences in the incidence of adverse side effects among groups. Patient satisfaction with pain management was similar in all groups. Local infiltration analgesia alone or followed by continuous infusion of ropivacaine as part of multimodal analgesia provides no additional analgesic benefit or reduction in opioid consumption compared with placebo following total hip arthroplasty. Therapeutic level I. See Instructions for Authors for a complete description of levels of evidence.

Mechanisms for vasopressin effects on intraocular pressure in anesthetized rats

NASA Technical Reports Server (NTRS)

Balaban, C. D.; Palm, D. E.; Shikher, V.; Searles, R. V.; Keil, L. C.; Severs, W. B.

1997-01-01

Continuous intracameral infusions of a balanced salt solution (0.175 microliter min-1) have been reported to raise intraocular pressure (IOP) in anesthetized rats. Palm et al. (1995) previously reported that this effect was attenuated significantly by inclusion of arginine-vasopressin (AVP, 10 ng 0.175 microliter-1) in the infusate. This study used experimental and computer simulation methods to investigate factors underlying these changes in IOP. First, constant intracameral infusions of artificial cerebrospinal fluid (aCSF) at different fixed rates (0.049-0.35 microliter min-1) were used to estimate the outflow resistance. Secondly, IOP responses were measured during an 2 hr intracameral infusion of either aCSF or AVP that was the sum of a small constant component (0.05 microliter min-1) and a larger periodic component (0.25 microliter min-1, cycling for 4 min on, then 4 min off); the mean infusion rate was 0.175 microliter min-1. As shown previously for 0.175 microliter min-1 constant infusions, the periodic aCSF infusion induced a significant rise in IOP that was attenuated by AVP administration. Complex demodulation analysis and the estimated gain parameter of a second order transfer function fit to the periodic responses indicated that outflow resistance increased significantly during the infusions in both aCSF and AVP groups, but that the indices of resistance did not differ significantly between aCSF and AVP infused eyes. This finding implies that changes in outflow resistance do not explain the difference in IOP responses to intracameral aCSF and AVP. The two responses differed significantly, though, in damping factors, such that the aCSF responses were considerably more underdamped than the AVP responses. It is hypothesized that aCSF-induced increase in IOP reflects both (1) a small component reflecting increased outflow resistance and (2) a larger non-resistive component. Since the non-resistive component is insensitive to pretreatment with acetazolamide, it is suggested that the aCSF-induced elevation in IOP reflects primarily vascular perfusion changes that are reduced by local vasoconstrictor actions of AVP. The latter mechanism likely maintains vascular perfusion of the globe when intraocular hypertension develops.

Use of nitroglycerin by bolus prevents intensive care unit admission in patients with acute hypertensive heart failure.

PubMed

Wilson, Suprat Saely; Kwiatkowski, Gregory M; Millis, Scott R; Purakal, John D; Mahajan, Arushi P; Levy, Phillip D

2017-01-01

The purpose of this study was to compare health care resource utilization among patients who were given intravenous nitroglycerin for acute heart failure (AHF) in the emergency department (ED) by intermittent bolus, continuous infusion, or a combination of both. We retrospectively identified 395 patients that received nitroglycerin therapy in the ED for the treatment of AHF over a 5-year period. Patients that received intermittent bolus (n=124) were compared with continuous infusion therapy (n=182) and combination therapy of bolus and infusion (n=89). The primary outcomes were the frequency of intensive care unit (ICU) admission and hospital length of stay (LOS). On unadjusted analysis, rates of ICU admission were significantly lower in the bolus vs infusion and combination groups (48.4% vs 68.7% vs 83%, respectively; P<.0001) and median LOS (interquartile range) was shorter (3.7 [2.5-6.2 days]) compared with infusion (4.7 [2.9-7.1 days]) and combination (5.0 [2.9-6.7 days]) groups; P=.02. On adjusted regression models, the strong association between bolus nitroglycerin and reduced ICU admission rate remained, and hospital LOS was 1.9 days shorter compared with infusion therapy alone. Use of intubation (bolus [8.9%] vs infusion [8.8%] vs combination [16.9%]; P=.096) and bilevel positive airway pressure (bolus [26.6%] vs infusion [20.3%] vs combination [29.2%]; P=.21) were similar as was the incidence of hypotension, myocardial injury, and worsening renal function. In ED patients with AHF, intravenous nitroglycerin by intermittent bolus was associated with a lower ICU admission rate and a shorter hospital LOS compared with continuous infusion. Copyright © 2016 Elsevier Inc. All rights reserved.

Regular intermittent bolus provides similar incidence of maternal fever compared with continuous infusion during epidural labor analgesia.

PubMed

Feng, Shan-Wu; Xu, Shi-Qin; Ma, Li; Li, Cai-Juan; Wang, Xian; Yuan, Hong-Mei; Wang, Fu-Zhou; Shen, Xiao-Feng; Ding, Zheng-Nian

2014-10-01

To compare the effects of regular intermittent bolus versus continuous infusion for epidural labor analgesia on maternal temperature and serum interleukin-6 (IL-6) level. This randomized trial was performed in Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu Province, China between October 2012 and February 2014. Either regular intermittent bolus (RIB, n=66) or continuous infusion (CI, n=66) was used for epidural labor analgesia. A bolus dose (10 ml of 0.08% ropivacaine + 0.4 ug·ml-1 sufentanil) was manually administrated once an hour in the RIB group, whereas the same solution was continuously infused at a constant rate of 10 ml·h-1 in the CI group. Maternal tympanic temperature and serum IL-6 level were measured hourly from baseline to one hour post partum. The incidences of fever (>/=38 degree celsius ) were calculated. The incidence of maternal fever was similar between the 2 groups. There was a rising trend in mean temperature over time in both groups, but no statistical difference was detected between the groups at respective time points; maternal serum IL-6 showed similar changes. Compared with continuous infusion, regular intermittent bolus presents with the same incidence of maternal fever for epidural labor analgesia. Interleukin-6 elevation could be involved in mean maternal temperature increase. 

21 CFR 870.1800 - Withdrawal-infusion pump.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Withdrawal-infusion pump. 870.1800 Section 870.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Diagnostic Devices § 870.1800 Withdrawal-infusion...

The use of an "unnatural" prostaglandin in the termination of pregnancy.

PubMed

Gillespie, A; Beazley, J M; van Dorp, D A

1971-04-01

An unnatural prostaglandin (PG) (prepared by biosynthesis using the method described by Vonkerman et al.) was used to terminate midtrimester pregnancy in 3 primiparous patients aged 21-24. The PG was administered intravenously using a Palmer slow infusion pump. The patients were monitored continuously with particular attention given to pulse, respiration, blood pressure, uterine contractions and cervical dilatation. All 3 cases successfully aborted. Effective infusion rate was similar to that of PGE1 and PGE2 (5-6 mcg/minute) and side effects were trivial (minimal skin flushing, vomiting, mild urticarial reaction). 2 of the patients aborted 8 and 22 hours after infusion stopped without being conscious of continuing uterine activity; the 3rd patient necessitated infusion on the 2nd day and exhibited increased response to the infusion; however, the PG supply was exhausted and syntocinon infusion facilitated the complete abortion. This study shows that this synthetic prostaglandin containing an uneven number of carbon atoms is pharmacologically active and can induce contractions in the intact human pregnant uterus.

Performance of the bispectral index during electrocautery.

PubMed

Chan, Matthew T V; Ho, Sin Shing; Gin, Tony

2012-01-01

The electroencephalogram contains small electrical signals that are vulnerable to contamination from high-frequency noise during electrocautery. The bispectral index (BIS) monitor incorporated hardware and software changes to eliminate artifacts, thus allowing BIS monitoring even in the presence of electrocautery. We evaluated the accuracy of BIS to measure anesthetic effect during electrocautery interference. Anesthesia was induced and maintained with target-controlled infusions of propofol (3 μg/mL) and remifentanil (4 ng/mL). After baseline BIS recordings, "simulated" electrocautery interference was induced continuously for 20 minutes. Five minutes after the start of electrocautery, propofol infusion was increased to achieve an effect site concentration of 6 μg/mL. Patients remained undisturbed during the study. BIS values and signal quality index were recorded continuously. During electrocautery, there was a significant decrease in signal quality index (mean difference: 16.9; 95% confidence intervals: 15.9-17.9; P<0.001). There was, however, no change in BIS value even after a step increase in propofol infusion from 3 to 6 μg/mL (P=0.93). In 22% of the patients there was a paradoxical increase in BIS values after doubling of propofol concentration. Following cessation of electrocautery, there was a prompt decrease in BIS (P<0.001), indicating a lack of response to the change in anesthetic depth during electrocautery. Rejecting and filtering artifacts from electrocautery interference reduced the ability of BIS to respond to a change in anesthetic depth. BIS values during electrocautery should be interpreted with caution.

Use of a Tea Infuser to Submerge Low-Density Dry Ice

ERIC Educational Resources Information Center

Fictorie, Carl P.; Vitz, Ed

2004-01-01

A simple tea infuser is obtained and been used as a container for the dry ice to simulate the effect from high-density dry ice. The tea infuser is a simple, low cost device to allow instructors with access to dry ice makers to effectively use the interesting demonstration.

Apparent lack of cross-reactivity for infusion-related reactions between two forms of lipid-based amphotericin B.

PubMed

Buckley, Mitchell S; Anderson, Clint S; Patel, Shardool A; Yerondopoulos, Melanie J; Wicks, Laura M; Martin, Mary T

2013-06-15

The case of a patient who experienced probable infusion-related reactions to amphotericin B lipid complex (ABLC) but tolerated continued amphotericin B therapy after a switch to an alternative lipid-based formulation is reported. A 28-year-old immunocompromised man with pneumonia, respiratory failure, and neutropenic fever was initiated on ABLC and other antibiotics for suspected invasive aspergillosis. Due to the patient's deteriorating renal function, the use of amphotericin B was deemed preferable to the standard therapy for invasive aspergillosis (voriconazole) even though he had experienced likely infusion-related reactions to ABLC on two prior occasions. During the infusion of ABLC, significant increases in the man's temperature, respiratory rate, systolic blood pressure, and heart rate were observed. Although those symptoms were suspected to be infusion related, it was decided that continuing amphotericin B therapy with an alternative lipid-based form of the drug was the best course of action. After the patient was switched to liposomal amphotericin B one day later, no further infusion-related adverse reactions were noted for the duration of therapy. While this case suggests that adverse reactions to one type of amphotericin B might not occur with the use of an alternative formulation, further research is needed to better define the potential for cross-reactivity among various forms of amphotericin B and related safe-infusion practices. A patient with invasive aspergillosis who experienced likely infusion- related reactions to ABLC was able to tolerate continued amphotericin B therapy after a switch to the liposomal formulation.

A Novel Approach to Improving Fat Delivery in Neonatal Enteral Feeding

PubMed Central

Jarjour, Jane; Juarez, Alexa M.; Kocak, Denizen K.; Liu, Nathan J.; Tabata, Mika M.; Hawthorne, Keli M.; Ramos, Renata F.; Abrams, Steven A.

2015-01-01

Continuous infusion systems used for enteral nutrition support in the neonatal intensive care unit deliver as little as 60% of the fat in human milk to the neonate. This study determined the effect of mixing common feedings for preterm infants in the feeding bag and tubing on fat losses during enteral feeding. Laboratory models were developed to assess the contribution of various mixing techniques to delivered fat content. Fat content was measured periodically during feeding and compared to baseline measurements. A multistage approach incorporating a feeding bag inverter and a tubing circulation loop delivered >90% of milk fat when used in conjunction with a commercial continuous infusion system. With unfortified human milk, this approach delivered 91.9% ± 1.5% of fat content over a one hour feed, significantly greater (p < 0.01) than 77.5% ± 2.2% delivered by continuous infusion controls (Mean ± SEM). With fortified human milk, this approach delivered 92.1% ± 2.4% of fat content, significantly greater (p < 0.01) than 79.4% ± 1.0% delivered by a non-adapted infusion system (Mean ± SEM). Mixing human milk during continuous infusion improves fat delivery, which may improve nutrition and growth outcomes in low birth weight neonates. PMID:26110253

[Ambulatory continuous intravenous infusion of fluorouracil: a feasible palliative form of chemotherapy].

PubMed

van Hoef, M E; Zonnenberg, B A; de Graeff, A; van Milligen de Wit, A W; Tjia, P; Neijt, J P

1991-03-30

A study to evaluate the feasibility and toxicity of outpatient continuous intravenous infusion of fluorouracil (5-FU) was initiated at the department of Medical Oncology of the University Hospital of Utrecht. To this purpose a subcutaneous drug delivery system (Port-a-Cath) was implanted in 36 patients with various advanced cancers. Of these patients 83% had received prior chemotherapy (including 5-FU in 62%). Ambulatory continuous-infusion pumps were used to administer 5-FU in a dosage of 300 mg/m2/24 h. The treatment was continued until tumour progression was seen, and it was interrupted in case of toxicity grade 2 or more (WHO criteria). A Port-a-Cath was implanted 37 times in the 36 patients. The main complications of this infusion system were pneumothorax (2/37), arrhythmia (1/37), catheter sepsis (2/37) and thrombosis (2/37); they were easily managed. The toxicity and feasibility of this treatment were evaluable in 30 patients. They received a median of 44 g 5-FU (range 11-136, 5 g, mean 281 mg/m2/24 h) during a median infusion time of 12 weeks (range 4-32 w). Side effects were encountered in 70% of the patients and consisted of the hand-foot syndrome (14/30), nausea and vomiting (8/30), diarrhoea (8/30) and stomatitis (7/30). The toxicity was completely reversible after a short interruption of the chemotherapy. The treatment was tolerated well, and good palliation was attained in 22 of 30 patients. The best response was seen in patients with colon and breast cancer. We conclude that continuous infusion of 5-FU is a reliable outpatient chemotherapy even in this category of patients.

Continuous intra-arterial nimodipine infusion in patients with severe refractory cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a feasibility study and outcome results.

PubMed

Bele, Sylvia; Proescholdt, Martin A; Hochreiter, Andreas; Schuierer, Gerhard; Scheitzach, Judith; Wendl, Christina; Kieninger, Martin; Schneiker, Andre; Bründl, Elisabeth; Schödel, Petra; Schebesch, Karl-Michael; Brawanski, Alexander

2015-12-01

Severe cerebral vasospasm is a major cause of death and disability in patients with aneurysmal subarachnoid hemorrhage. No causative treatment is yet available and hypertensive hypervolemic therapy (HHT) is often insufficient to avoid delayed cerebral ischemia and neurological deficits. We compared patients receiving continuous intra-arterial infusion of the calcium-antagonist nimodipine with a historical group treated with HHT and oral nimodipine alone. Between 0.5 and 1.2 mg/h of nimodipine were continuously administered by intra-arterial infusion via microcatheters either into the internal carotid or vertebral artery or both, depending on the areas of vasospasm. The effect was controlled via multimodal neuromonitoring and transcranial Doppler sonography. Outcome was determined by means of the Glasgow Outcome Scale at discharge and 6 months after the hemorrhage and compared to a historical control group. Twenty-one patients received 28 intra-arterial nimodipine infusions. Six months after discharge, the occurrence of cerebral infarctions was significantly lower (42.6 %) in the nimodipine group than in the control group (75.0 %). This result was reflected by a significantly higher proportion (76.0 %) of patients with good outcome in the nimodipine-treated group, when compared to 10.0 % good outcome in the control group. Median GOS was 4 in the nimodipine group and 2 in the control group (p = 0.001). Continuous intra-arterial nimodipine infusion is an effective treatment for patients with severe cerebral vasospasm who fail to respond to HHT and oral nimodipine alone. Key to the effective administration of continuous intra-arterial nimodipine is multimodal neuromonitoring and the individual adaptation of dosage and time of infusion for each patient.

Continuous 28-day iododeoxyuridine infusion and hyperfractionated accelerated radiotherapy for malignant glioma: a phase I clinical study.

PubMed

Schulz, Craig A; Mehta, Minesh P; Badie, Benham; McGinn, Cornelius J; Robins, H Ian; Hayes, Lori; Chappell, Rick; Volkman, Jen; Binger, Kim; Arzoomanian, Rhoda; Simon, Kris; Alberti, Dona; Feierabend, Christine; Tutsch, Kendra D; Kunugi, Keith A; Wilding, George; Kinsella, Timothy J

2004-07-15

To investigate the maximal tolerated dose of a continuous 28-day iododeoxyuridine (IUdr) infusion combined with hyperfractionated accelerated radiotherapy (HART); to analyze the percentage of IUdr-thymidine replacement in peripheral granulocytes as a surrogate marker for IUdr incorporation into tumor cells; to measure the steady-state serum IUdr levels; and to assess the feasibility of continuous IUdr infusion and HART in the management of malignant glioma. Patients were required to have biopsy-proven malignant glioma. Patients received 100 (n = 4), 200 (n = 3), 300 (n = 3), 400 (n = 6), 500 (n = 4), 625 (n = 5), or 781 (n = 6) mg/m(2)/d of IUdr by continuous infusion for 28 days. HART was started 7 days after IUdr initiation. The total dose was 70 Gy (1.2 Gy b.i.d. for 25 days with a 10-Gy boost [2.0 Gy for 5 Saturdays]). Weekly assays were performed to determine the percentage of IUdr-DNA replacement in granulocytes and serum IUdr levels using standard high performance liquid chromatography methods. Standard Phase I toxicity methods were used. Between June 1994 and August 1999, 31 patients were enrolled. No patient had Grade 3 or worse HART toxicity. Grade 3 or greater IUdr toxicity predominantly included neutropenia (n = 3), thrombocytopenia (n = 3), and elevated liver function studies (n = 3). The maximal tolerated dose was 625 mg/m(2)/d. Thymidine replacement in the peripheral granulocytes peaked at 3 weeks and increased with the dose (maximal thymidine replacement 4.9%). The steady-state plasma IUdr level increased with the dose (maximum, 1.5 microM). In our study, continuous long-term IUdr i.v. infusion had a maximal tolerated dose of 625 mg/m(2)/d. Granulocyte incorporation data verified the concept that prolonged IUdr infusion results in IUdr-DNA replacement that corresponds to a high degree of cell labeling. IUdr steady-state plasma levels increased with increasing dose and attained levels needed for clinical radiosensitization. Continuous IUdr infusion and HART were both feasible and well tolerated.

Ad hoc versus standardized admixtures for continuous infusion drugs in neonatal intensive care: cognitive task analysis of safety at the bedside.

PubMed

Brannon, Timothy S

2006-01-01

Continuous infusion intravenous (IV) drugs in neonatal intensive care are usually prepared based on patient weight so that the dose is readable as a simple multiple of the infusion pump rate. New safety guidelines propose that hospitals switch to using standardized admixtures of these drugs to prevent calculation errors during ad hoc preparation. Extended hierarchical task analysis suggests that switching to standardized admixtures may lead to more errors in programming the pump at the bedside.

Ad Hoc versus Standardized Admixtures for Continuous Infusion Drugs in Neonatal Intensive Care: Cognitive Task Analysis of Safety at the Bedside

PubMed Central

Brannon, Timothy S.

2006-01-01

Continuous infusion intravenous (IV) drugs in neonatal intensive care are usually prepared based on patient weight so that the dose is readable as a simple multiple of the infusion pump rate. New safety guidelines propose that hospitals switch to using standardized admixtures of these drugs to prevent calculation errors during ad hoc preparation. Extended hierarchical task analysis suggests that switching to standardized admixtures may lead to more errors in programming the pump at the bedside. PMID:17238482

Tolerability of ketorolac administered via continuous subcutaneous infusion for cancer pain: a preliminary report.

PubMed

De Conno, F; Zecca, E; Martini, C; Ripamonti, C; Caraceni, A; Saita, L

1994-02-01

We evaluated the local and systemic tolerability of ketorolac administered through continuous subcutaneous infusion in ten cancer patients. The patients were monitored daily for the severity and duration of pain, and the development of other symptoms. The duration of injection site varied from 1 to more than 7 days. No patients complained of local discomfort or pain. Mild local bleeding at the site of drug injection was observed in seven cases. No increase in the intensity of symptoms was observed during the infusion of ketorolac.

40 CFR 721.10706 - Infused carbon nanostructures (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Infused carbon nanostructures (generic). 721.10706 Section 721.10706 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10706 Infused...

40 CFR 721.10287 - Infused carbon nanostructures (generic).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Infused carbon nanostructures (generic). 721.10287 Section 721.10287 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10287 Infused...

40 CFR 721.10287 - Infused carbon nanostructures (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Infused carbon nanostructures (generic). 721.10287 Section 721.10287 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10287 Infused...

Minimum infusion rate and adrenocortical function after continuous infusion of the novel etomidate analog ET-26-HCl in rats.

PubMed

Jiang, Junli; Wang, Bin; Zhu, Zhaoqiong; Yang, Jun; Liu, Jin; Zhang, Wensheng

2017-01-01

Because etomidate induces prolonged adrenal suppression, even following a single bolus, its use as an infused anesthetic is limited. Our previous study indicated that a single administration of the novel etomidate analog methoxyethyletomidate hydrochloride (ET-26-HCl) shows little suppression of adrenocortical function. The aims of the present study were to (1) determine the minimum infusion rate of ET-26-HCl and compare it with those for etomidate and cyclopropyl-methoxycarbonylmetomidate (CPMM), a rapidly metabolized etomidate analog that is currently in clinical trials and (2) to evaluate adrenocortical function after a continuous infusion of ET-26-HCl as part of a broader study investigating whether this etomidate analog is suitable for long infusion in the maintenance of anesthesia. The up-and-down method was used to determine the minimum infusion rates for ET-26-HCl, etomidate and CPMM. Sprague-Dawley rats ( n  = 32) were then randomly divided into four groups: etomidate, ET-26-HCl, CPMM, and vehicle control. Rats in each group were infused for 60 min with one of the drugs at its predetermined minimum infusion rate. Blood samples were drawn initially and then every 30 min after drug infusion to determine the adrenocorticotropic hormone-stimulated concentration of serum corticosterone as a measure of adrenocortical function. The minimum infusion rates for etomidate, ET-26-HCl and CPMM were 0.29, 0.62, and 0.95 mg/kg/min, respectively. Compared with controls, etomidate decreased serum corticosterone, as expected, whereas serum corticosterone concentrations following infusion with the etomidate analogs ET-26-HCl or CPMM were not significantly different from those in the control group. The corticosterone concentrations tended to be reduced for the first hour following ET-26-HCl infusion (as compared to vehicle infusion); however, this reduction did not reach statistical significance. Thus, further studies are warranted examining the practicability of using ET-26-HCl as an infused anesthetic.

Continuous infusion vs. bolus dosing: implications for beta-lactam antibiotics.

PubMed

Mohd Hafiz, Abdul-Aziz; Staatz, C E; Kirkpatrick, C M J; Lipman, J; Roberts, J A

2012-01-01

Beta-lactam antibiotics display time-dependant pharmacodynamics whereby constant antibiotic concentrations rather than high peak concentrations are most likely to result in effective treatment of infections caused by susceptible bacteria. Continuous administration has been suggested as an alternative strategy, to conventional intermittent dosing, to optimise beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) properties. With the availability of emerging data, we elected to systematically investigate the published literature describing the comparative PK/PD and clinical outcomes of beta-lactam antibiotics administered by continuous or intermittent infusion. We found that the studies have been performed in various patient populations including critically ill, cancer and cystic fibrosis patients. Available in vitro PK/PD data conclusively support the administration of beta-lactams via continuous infusion for maximizing bacterial killing from consistent attainment of pharmacodynamic end-points. In addition, clinical outcome data supports equivalence, even with the use of a lower dose by continuous infusion. However, the present clinical data is limited with small sample sizes common with insufficient power to detect advantages in favour of either dosing strategy. With abundant positive pre-clinical data as well as document in vivo PK/PD advantages, large multi-centre trials are needed to describe whether continuous administration of beta-lactams is truly more effective than intermittent dosing.

Use of a physostigmine continuous infusion for the treatment of severe and recurrent antimuscarinic toxicity in a mixed drug overdose.

PubMed

Phillips, Michelle A; Acquisto, Nicole M; Gorodetsky, Rachel M; Wiegand, Timothy J

2014-06-01

Physostigmine was once a widely used antidote for the treatment of antimuscarinic toxicity. However, reports describing the association of physostigmine with asystole and seizures in severe tricyclic antidepressant poisoning resulted in a decrease in use. Recent literature has demonstrated that physostigmine is a safe and effective antidote for the treatment of antimuscarinic toxicity. There are only two previously published articles regarding the use of physostigmine administered as a continuous intravenous infusion for persistent antimuscarinic toxicity. We present a case of physostigmine continuous infusion for the treatment of antimuscarinic symptoms in a polydrug overdose due to the ingestion of diphenhydramine along with bupropion, citalopram, acetaminophen, and naproxen. A 13-year-old female presented with hyperthermia, myoclonus and rigidity, hallucinations, severe agitation, and antimuscarinic toxicity including inability to sweat after a polydrug overdose. Several doses of lorazepam were administered followed by physostigmine which produced resolution of hallucinations and attenuation of the antimuscarinic symptoms including perspiration, temperature improvement, and decreased agitation. After periods of improvement and recurrence of antimuscarinic effects, a continuous infusion of physostigmine was administered at 2 mg/h and continued for almost 8 h to maintain attenuation of symptoms. GABAergic agents including lorazepam and phenobarbital were used later in the hospital course for presumed symptoms of serotonergic and adrenergic toxicity after resolution of antimuscarinic effects. The patient did not experience any adverse effects of physostigmine administration. Physostigmine administered as a continuous infusion may be a reasonable treatment option for severe and recurrent symptoms related to antimuscarinic toxicity.

The Experiences of School Nurses Caring for Students Receiving Continuous Subcutaneous Insulin Infusion Therapy

ERIC Educational Resources Information Center

Darby, Wendy

2006-01-01

Diabetes mellitus is the most common metabolic disorder in childhood. Today, children with diabetes are receiving new technologically advanced treatment options, such as continuous subcutaneous insulin infusion (CSII) therapy. School nurses are the primary health caregivers of children with diabetes during school hours. Therefore, it is important…

User's guide to resin infusion simulation program in the FORTRAN language

NASA Technical Reports Server (NTRS)

Weideman, Mark H.; Hammond, Vince H.; Loos, Alfred C.

1992-01-01

RTMCL is a user friendly computer code which simulates the manufacture of fabric composites by the resin infusion process. The computer code is based on the process simulation model described in reference 1. Included in the user's guide is a detailed step by step description of how to run the program and enter and modify the input data set. Sample input and output files are included along with an explanation of the results. Finally, a complete listing of the program is provided.

Continuous Lidocaine Infusions to Manage Opioid-Refractory Pain in a Series of Cancer Patients in a Pediatric Hospital.

PubMed

Gibbons, Kathleen; DeMonbrun, Andrea; Beckman, Elizabeth J; Keefer, Patricia; Wagner, Deb; Stewart, Margaret; Saul, D'Anna; Hakel, Stephanie; Liu, My; Niedner, Matthew

2016-07-01

Research on the safety and efficacy of continuous lidocaine infusions (CLIs) for the treatment of pain in the pediatric setting is limited. This article describes a series of pediatric oncology patients who received lidocaine infusions for refractory, longstanding, cancer-related pain. This is a retrospective review of patients who underwent lidocaine infusions to manage severe, opioid-refractory, cancer-related pain. Four patients ranging in age from 8 to 18 years were admitted to a pediatric hospital for their medical conditions and/or pain management. Structured chart review established demographic and diagnosis information, infusion rates, side effects, and efficacy of infusions in providing pain relief. Lidocaine bolus doses, infusion rates, serum concentrations, and subjective pain scores were analyzed. Median pain scores prior to lidocaine infusions were 8/10, falling to 2/10 at the infusion termination (P < 0.003), and rising to 3/10 in the first 24 hr after lidocaine (P < 0.029 compared to preinfusion pain). The infusions were generally well tolerated, with few side effects noted. In most cases, the improvement in pain scores persisted beyond termination of the infusion. CLIs were a helpful adjuvant in the four cases presented and may be an effective therapy for a more diverse array of refractory cancer pain. The majority of patients experienced pain relief well beyond the metabolic elimination of the lidocaine, corroborating a modulation effect on pain windup. Additional research regarding infusion rates, serum concentrations, side effects, and outpatient follow-up in a larger group of patients will provide additional insight into the role and safety of this therapy in children. © 2016 Wiley Periodicals, Inc.

A systematic review on clinical benefits of continuous administration of beta-lactam antibiotics.

PubMed

Roberts, Jason A; Webb, Steven; Paterson, David; Ho, Kwok M; Lipman, Jeffrey

2009-06-01

The clinical benefits of extended infusion or continuous infusion of beta-lactam antibiotics remain controversial. We systematically reviewed the literature to determine whether any clinical benefits exist for administration of beta-lactam antibiotics by extended or continuous infusion. PubMed (January 1950 to November 2007), EMBASE (1966 to November 2007), and the Cochrane Controlled Trial Register were searched (updated November 2007). Randomized controlled trials (RCTs) were meta-analyzed, and observational studies were described by two unblinded reviewers. A total of 846 patients from eligible prospective randomized controlled studies were included in the meta-analysis. Two observational studies were deemed appropriate for description. A meta-analysis of prospective RCTs was undertaken using Review Manager. Among a total of 59 potentially relevant studies, 14 RCTs involving a total of 846 patients from nine countries were deemed appropriate for meta-analysis. The use of continuous infusion of a beta-lactam antibiotic was not associated with an improvement in clinical cure (n = 755 patients; odds ratio: 1.04, 95% confidence interval: 0.74-1.46, p = 0.83, I = 0%) or mortality (n = 541 patients; odds ratio: 1.00, 95% confidence interval: 0.48-2.06, p = 1.00, I = 14.8%). All RCTs except one used a higher antibiotic dose in the bolus administration group. Two observational studies, not pooled because they did not meet the a priori criteria for meta-analysis, showed that beta-lactam administration by extended or continuous infusion was associated with an improvement in clinical cure. The difference in the results between the meta-analysis results and the observational studies could be explained by the bias created by a higher dose of antibiotic in the bolus group in the RCTs and because many of the RCTs only recruited patients with a low acuity of illness. The limited data available suggest that continuous infusion of beta-lactam antibiotics leads to the same clinical results as higher dosed bolus administration in hospitalized patients.

Direct numerical simulation of turbulent channel flow over a liquid-infused micro-grooved surface

NASA Astrophysics Data System (ADS)

Chang, Jaehee; Jung, Taeyong; Choi, Haecheon; Kim, John

2016-11-01

Recently a superhydrophobic surface has drawn much attention as a passive device to achieve high drag reduction. Despite the high performance promised at ideal conditions, maintaining the interface in real flow conditions is an intractable problem. A non-wetting surface, known as the slippery liquid-infused porous surface (SLIPS) or the lubricant-impregnated surface (LIS), has shown a potential for drag reduction, as the working fluid slips at the interface but cannot penetrate into the lubricant layer. In the present study, we perform direct numerical simulation of turbulent channel flow over a liquid-infused micro-grooved surface to investigate the effects of this surface on the interfacial slip and drag reduction. The flow rate of water is maintained constant corresponding to Reτ 180 in a fully developed turbulent channel flow, and the lubricant layer is shear-driven by the turbulent water flow. The lubricant layer is also simulated with the assumption that the interface is flat (i.e. the surface tension effect is neglected). The solid substrate in which the lubricant is infused is modelled as straight ridges using an immersed boundary method. DNS results show that drag reduction by the liquid-infused surface is highly dependent on the viscosity of the lubricant.

Transient central diabetes insipidus induced by ketamine infusion.

PubMed

Hatab, Sarah Z; Singh, Arun; Felner, Eric I; Kamat, Pradip

2014-12-01

Report a case of central diabetes insipidus (DI) associated with ketamine infusion. A 2-year-old girl with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and stable hypertrophic cardiomyopathy was admitted to the pediatric intensive care with pneumonia. She subsequently developed respiratory failure and required intubation. Continuous ketamine infusion was used for the sedation and facilitation of mechanical ventilation. Shortly after infusion of ketamine, the patient developed DI and responded appropriately to vasopressin. The Naranjo adverse drug reaction probability scale indicated a probable relationship between the development of central DI and ketamine. The most likely mechanism involves ketamine's antagonist action on N-methyl-d-aspartate receptors, resulting in inhibition of glutamate-stimulated arginine vasopressin release from the neurohypophysis. This is the second case report of ketamine-induced central DI and the only report in children. Clinicians who sedate children with continuous ketamine infusions should monitor patients for developing signs and symptoms of DI by measuring serum sodium and urine output prior to, during, and after ketamine infusion in order to make a timely diagnosis of this potentially serious complication. © The Author(s) 2014.

Safety and efficacy of intravenous labetalol for hypertensive crisis in infants and small children.

PubMed

Thomas, Christopher A; Moffett, Brady S; Wagner, Jeffrey L; Mott, Antonio R; Feig, Daniel I

2011-01-01

To determine the efficacy and safety of labetalol for hypertensive crisis in children ≤ 24 months of age. Retrospective chart review. Statistical analysis utilized analysis of variance for continuous data, chi-square tests for nominal data, and linear regression. A 737-bed pediatric teaching institution. Twenty-seven patients ≤ 24 months of age were treated with 37 intravenous infusions of labetalol, nicardipine, or nitroprusside for hypertensive crisis or hypertensive urgency. None. The primary end point consisted of time to 20% reduction in systolic blood pressure. Primary safety end points measured the prevalence of deleterious effects of labetalol. Continuous infusion of labetalol reduced mean systolic blood pressure by at least 20% in < 8 hrs. This effect was similar to nicardipine and nitroprusside infusions. The reported side effects were similar in each group. Patients receiving labetalol and presenting with ischemic or traumatic brain injury were likely to develop hypotension requiring infusion discontinuation. Continuous intravenous labetalol infusion is efficacious for treatment of hypertensive crisis in children ≤ 24 months of age. Aside from patients presenting with ischemic or traumatic brain injury, labetalol was safe to use in this population for hypertensive emergencies and had a satisfactory adverse effect profile. Labetalol may reach dose saturation at a much lower dose in young children in comparison to adults. Clinicians should use caution when initiating labetalol infusions in young patients with brain injury.

Dose requirements of continuous infusion of rocuronium and atracurium throughout orthotopic liver transplantation in humans

PubMed Central

Weng, Xiao-chuan; Zhou, Liang; Fu, Yin-yan; Zhu, Sheng-mei; He, Hui-liang; Wu, Jian

2005-01-01

Objective: To compare the dose requirements of continuous infusion of rocuronium and atracurium throughout orthotopic liver transplantation (OLT) in humans. Methods: Twenty male patients undergoing liver transplantation were randomly assigned to two comparable groups of 10 patients each to receive a continuous infusion of rocuronium or atracurium under intravenous balanced anesthesia. The response of adductor pollicis to train-of-four (TOF) stimulation of unlar nerve was monitored. The infusion rates of rocuronium and atracurium were adjusted to maintain T1/Tc ratio of 2%~10%. The total dose of each drug given during each of the three phases of OLT was recorded. Results: Rocuronium requirement, which were (0.468±0.167) mg/(kg·h) during the paleohepatic phase, decreased significantly during the anhepatic phase to (0.303±0.134) mg/(kg·h) and returned to the initial values at the neohepatic period ((0.429±0.130) mg/(kg·h)); whereas atracuruim requirements remained unchanged during orthotopic liver transplantation. Conclusions: This study showed that the exclusion of the liver from the circulation results in the significantly reduced requirement of rocuronium while the requirement of atracurium was not changed, which suggests that the liver is of major importance in the clearance of rocuronium. A continuous infusion of atracurium with constant rate can provide stable neuromuscular blockade during the three stages of OLT. PMID:16130187

Continuous subcutaneous delivery of medications for home care palliative patients-using an infusion set or a pump?

PubMed

Menahem, Sasson; Shvartzman, Pesach

2010-09-01

The purpose of this study was to evaluate safety, feasibility, and efficacy of continuous drug delivery by the subcutaneous route through a solution bag connected to an infusion set compared with an infusion pump in a home palliative care setting. Patients in need of continuous subcutaneous medication delivery for pain control, nausea, and/or vomiting were recruited. The study was designed as a double-blind, crossover study. The patient was connected to two parallel subcutaneous lines running simultaneously, connected together to a line entering the subcutaneous tissue. One line is connected to an infusion set and the other to a pump. The infusion set included a 500-cc solution bag connected to a 1.5-m plastic tube containing a drip chamber controlled by a roller clamp that is gravity driven without hyaluronidase. Active medications were randomly assigned to start in either administration method and switched after 24 h. An independent research assistant evaluated symptom control and side effects at baseline and every 24 h for 2 days using a structured questionnaire. Another independent research assistant connected the lines after adding medications and evaluated technical and clinical failures. Twenty-seven patients were recruited, and of them, 18 completed the study. Incidents in fluid administration were more common through the infusion set (18 times) compared to the pump (only twice). On the other hand, no clinical significant change was noted in the average symptom levels and side effects when medications were given through the infusion set versus the pump. No local edema or irritation was observed in either way of administration. In a home palliative care setting with a medical staff on call for 24 h, using medications for symptom control can be considered to be infused to a fluid solution bag through an infusion set instead of using a syringe driver or a pump when there is a responsible caregiver to follow up on the fluid. Subcutaneous constant drug delivery through a pump is more accurate.

Titrated propofol induction vs. continuous infusion in children undergoing magnetic resonance imaging.

PubMed

Cho, J E; Kim, W O; Chang, D J; Choi, E M; Oh, S Y; Kil, H K

2010-04-01

Propofol is the popular intravenous (i.v.) anaesthetic for paediatric sedation because of its rapid onset and recovery. We compared the efficacy and safety of a single dose and conventional infusion of propofol for sedation in children who underwent magnetic resonance imaging (MRI). This was a double-blind, randomized-controlled study. One hundred and sixty children were assigned to group I (single dose) or II (infusion). Sedation was induced with i.v. propofol 2 mg/kg, and supplemental doses of propofol 0.5 mg/kg were administered until adequate sedation was achieved. After the induction of sedation, we treated patients with a continuous infusion of normal saline at a rate of 0.3 ml/kg/h in group I and the same volume of propofol in group II. In case of inadequate sedation, additional propofol 0.5 mg/kg was administered and the infusion rate was increased by 0.05 ml/kg/h. Induction time, sedation time, recovery time, additional sedation and adverse events were recorded. Recovery time was significantly shorter in group I compared with group II [0 (0-3) vs. 1 (0-3), respectively, P<0.001]. Group I (single dose) had significantly more patients with recovery time 0 compared with group II (infusion) (65/80 vs. 36/80, respectively, P<0.001). Induction and sedation times were not significantly different between groups. There was no significant difference in the frequency of additional sedation and adverse events between groups. A single dose of propofol without a continuous infusion can provide appropriate sedation in children undergoing MRI for <30 min.

Vascular Access System for Continuous Arterial Infusion of a Protease Inhibitor in Acute Necrotizing Pancreatitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganaha, Fumikiyo; Yamada, Tetsuhisa; Yorozu, Naoya

1999-09-15

We used a vascular access system (VAS) for continuous arterial infusion (CAI) of a protease inhibitor in two patients with acute necrotizing pancreatitis. The infusion catheter was placed into the dorsal pancreatic artery in the first patient and into the gastroduodenal artery in the second, via a femoral artery approach. An implantable port was then connected to the catheter and was secured in a subcutaneous pocket prepared in the right lower abdomen. No complications related to the VAS were encountered. This system provided safe and uncontaminated vascular access for successful CAI for acute pancreatitis.

Multiple Intravenous Infusions Phase 2a: Ontario Survey

PubMed Central

Fan, Mark; Koczmara, Christine; Masino, Caterina; Cassano-Piché, Andrea; Trbovich, Patricia; Easty, Anthony

2014-01-01

Background Research conducted in earlier phases of this study prospectively identified a number of concerns related to the safe administration of multiple intravenous (IV) infusions in Ontario hospitals. Objective To investigate the potential prevalence of practices or policies that may contribute to the patient safety risks identified in Phase 1b of this study. Data Sources and Review Methods Sixty-four survey responses were analyzed from clinical units where multiple IV infusions may occur (e.g., adult intensive care units). Survey questions were organized according to the topics identified in Phase 1b as potential contributors to patient harm (e.g., labelling practices, patient transfer practices, secondary infusion policies). Results Survey results indicated suboptimal practices and policies in some clinical units, and variability in a number of infusion practices. Key areas of concern included the following: use of primary IV tubing without back check valves when administering secondary infusions administration of secondary infusions with/as high-alert continuous IV medications potential confusion about how IV tubing should be labelled to reflect replacement date and time interruptions to IV therapy due to IV pump and/or tubing changes when patients are transferred between clinical units coadministration of continuous or intermittent infusions on central venous pressure monitoring ports variability in respondents’ awareness of the infusion pump's bolus capabilities Limitations Due to the limited sample size, survey responses may not be representative of infusion practices across Ontario. Answers to some questions indicated that the intent of the questions might have been misunderstood. Due to a design error, 1 question about bolus administration methods was not shown to as many respondents as appropriate. Conclusions The Ontario survey revealed variability in IV infusion practice across the province and potential opportunities to improve safety. PMID:26257837

Attenuation of Multiple Organ Damage by Continuous Low-Dose Solvent-Free Infusions of Resveratrol after Severe Hemorrhagic Shock in Rats

PubMed Central

Kirsch, Michael; Petrat, Frank

2017-01-01

Therapeutic effects of continuous intravenous infusions of solvent-free low doses of resveratrol on organ injury and systemic consequences resulting from severe hemorrhagic shock in rats were studied. Hemorrhagic shock was induced by withdrawing arterial blood until a mean arterial blood pressure (MAP) of 25–30 mmHg was reached. Following a shock phase of 60 min, rats were resuscitated with the withdrawn blood plus lactated Ringer’s. Resveratrol (20 or 60 μg/kg × h) was continuously infused intravenously starting with the resuscitation phase (30 min) and continued until the end of the experiment (total treatment time 180 min). Animals of the shock control group received 0.9% NaCl solution. After the observation phase (150 min), rats were sacrificed. Resveratrol significantly stabilized the MAP and peripheral oxygen saturation after hemorrhagic shock, decreased the macroscopic injury of the small intestine, significantly attenuated the shock-induced increase in tissue myeloperoxidase activity in the small intestine, liver, kidney and lung, and diminished tissue hemorrhages (particularly in the small intestine and liver) as well as the rate of hemolysis. Already very low doses of resveratrol, continuously infused during resuscitation after severe hemorrhagic shock, can significantly improve impaired systemic parameters and attenuate multiple organ damage in rats. PMID:28817064

Long-Term Antihyperalgesic and Opioid-Sparing Effects of 5-Day Ketamine and Morphine Infusion ("Burst Ketamine") in Diabetic Neuropathic Rats.

PubMed

Mak, Plato; Broadbear, Jillian H; Kolosov, Anton; Goodchild, Colin S

2015-09-01

"Burst ketamine" (BK) is the long-term infusion of subanesthetic ketamine in combination with an opioid. It is used clinically with mixed success to provide long-term pain relief and improve opioid response in patients. BK has not been simulated preclinically, therefore, its effectiveness was investigated in an animal model of neuropathic pain--streptozotocin-induced diabetic neuropathy. Diabetic neuropathic rats were randomized to receive a subcutaneous infusion of ketamine 20 mg/kg/day plus morphine 20 mg/kg/day (BK), either drug alone at the same dose, or sham treatment. Drugs were administered continuously over 5 days via osmotic minipump. Antihyperalgesic effects and antinociceptive responsiveness to morphine (0.625-10 mg/kg, i.p.) were assessed at 2, 4, 6, and 12 weeks post-treatment using paw withdrawal latency (PWL) from noxious heat (thermal hyperalgesia) and mechanical touch (tactile allodynia). Antihyperalgesic effects with significant increases in PWL from noxious heat occurred following BK and ketamine-only infusion, persisting 12 and 4 weeks, respectively. Opioid-sparing effects from noxious heat with increased sensitivity to morphine analgesia also occurred for 6 weeks after BK and 2 weeks after ketamine treatment; acute treatment with the maximum nonsedating dose of morphine (5 mg/kg) produced an antinociceptive effect in these two groups, but not in sham-treated rats. In morphine-only infusion rats, hyperalgesia and opioid insensitivity were both increased. This is the first preclinical study to use a model of neuropathic pain to demonstrate the utility of the BK procedure for delivering a long-lasting reduction in hyperalgesia and improved antinociceptive responsiveness to opioids. Wiley Periodicals, Inc.

Stimulation of skeletal muscle protein synthesis in neonatal pigs by long-term infusion of leucine is amino acid dependent

USDA-ARS?s Scientific Manuscript database

Infusing leucine for 1 hr increases skeletal muscle protein synthesis in neonatal pigs, but this is not sustained for 2 h unless the leucine-induced fall in amino acids is prevented. We aimed to determine whether continuous leucine infusion can stimulate protein synthesis for a prolonged period whe...

Duodenal supply of glutamate and casein both improve intestinal starch digestion in cattle but by apparently different mechanisms.

PubMed

Brake, D W; Titgemeyer, E C; Anderson, D E

2014-09-01

Greater postruminal flows of protein increase small intestinal starch digestion in cattle. Our objective was to determine if small intestinal starch digestion is increased by duodenal supplementation of AA. We fed 5 duodenally and ileally cannulated steers a low-starch soybean hull-based diet in 5 × 5 Latin square designs and provided continuous duodenal infusion of raw cornstarch in combination with AA or casein and measured small intestinal starch digestion. In Exp. 1 treatments were continuous duodenal infusion of 1) no supplement (control), 2) casein (400 g/d), 3) crystalline AA similar in amount and AA composition to the casein (CASAA), 4) crystalline nonessential AA similar to those provided by casein, or 5) crystalline essential AA similar to those provided by casein. In Exp. 2 treatments were continuous duodenal infusion of 1) no supplement (control), 2) casein (400 g/d), 3) Glu (133 g/d), 4) Phe and Trp plus Met (30.4, 6.5, and 17.5 g/d, respectively; PTM), or 5) a combination of Glu and PTM. Duodenal infusion of casein increased (P ≤ 0.05) small intestinal starch digestion. When CASAA was infused, small intestinal starch digestion was similar (P = 0.30) to casein infusion. Infusion of only nonessential AA tended to increase (P = 0.14) small intestinal starch digestion relative to the control, but infusion of essential AA alone did not affect (P = 0.84) small intestinal starch digestion. In addition, infusion of casein or CASAA increased ileal flows of ethanol-soluble starch (small-chain α-glycosides), but nonessential AA alone were not different than the control. Duodenal infusion of Glu increased (P ≤ 0.05) small intestinal starch digestion, whereas PTM did not. Neither Glu nor PTM increased ileal flow of ethanol-soluble starch, but Glu and PTM provided together tended (P = 0.07) to increase ileal flows of small chain α-glycosides. Our data suggest that Glu alone can increase small intestinal starch digestion in cattle similar to casein, but increases in small intestinal starch digestion in response to Glu are not associated with an increase in ileal flows of small chain α-glycosides.

A 7-day continuous infusion of PTH or PTHrP suppresses bone formation and uncouples bone turnover.

PubMed

Horwitz, Mara J; Tedesco, Mary Beth; Sereika, Susan M; Prebehala, Linda; Gundberg, Caren M; Hollis, Bruce W; Bisello, Alessandro; Garcia-Ocaña, Adolfo; Carneiro, Raquel M; Stewart, Andrew F

2011-09-01

Human in vivo models of primary hyperparathyroidism (HPT), humoral hypercalcemia of malignancy (HHM), or lactational bone mobilization for more than 48 hours have not been described previously. We therefore developed 7-day continuous-infusion models using human parathyroid hormone(1-34) [hPTH(1-34)] and human parathyroid hormone-related protein(1-36) [hPTHrP(1-36)] in healthy human adult volunteers. Study subjects developed sustained mild increases in serum calcium (10.0 mg/dL), with marked suppression of endogenous PTH(1-84). The maximal tolerated infused doses over a 7-day period (2 and 4 pmol/kg/h for PTH and PTHrP, respectively) were far lower than in prior, briefer human studies (8 to 28 pmol/kg/h). In contrast to prior reports using higher PTH and PTHrP doses, both 1,25-dihydroxyvitamin D(3) [1,25(OH)(2) D(3) ] and tubular maximum for phosphorus (TmP/GFR) remained unaltered with these low doses despite achievement of hypercalcemia and hypercalciuria. As expected, bone resorption increased rapidly and reversed promptly with cessation of the infusion. However, in contrast to events in primary HPT, bone formation was suppressed by 30% to 40% for the 7 days of the infusions. With cessation of PTH and PTHrP infusion, bone-formation markers abruptly rebounded upward, confirming that bone formation is suppressed by continuous PTH or PTHrP infusion. These studies demonstrate that continuous exposure of the human skeleton to PTH or PTHrP in vivo recruits and activates the bone-resorption program but causes sustained arrest in the osteoblast maturation program. These events would most closely mimic and model events in HHM. Although not a perfect model for lactation, the increase in resorption and the rebound increase in formation with cessation of the infusions are reminiscent of the maternal skeletal calcium mobilization and reversal that occur following lactation. The findings also highlight similarities and differences between the model and HPT. Copyright © 2011 American Society for Bone and Mineral Research.

Controlled Study of the Effects of Continuous Intrathecal Baclofen Infusion in Non-Ambulant Children with Cerebral Palsy

ERIC Educational Resources Information Center

Morton, Richard E.; Gray, Natalie; Vloeberghs, Michael

2011-01-01

Aim: To measure changes in children with severe spastic cerebral palsy (CP) after continuous intrathecal baclofen (ITB) infusion over 18 months and to compare the results with those of a comparison group awaiting treatment. Method: Thirty-eight children with severe spastic CP considered suitable for ITB were assessed when first seen, just before…

Numerical Simulations for Turbulent Drag Reduction Using Liquid Infused Surfaces

NASA Astrophysics Data System (ADS)

Arenas-Navarro, Isnardo

Numerical simulations of the turbulent flow over Super Hydrophobic and Liquid Infused Surfaces have been performed in this work. Three different textured surfaces have been considered: longitudinal square bars, transversal square bars and staggered cubes. The numerical code combines an immersed boundary method to mimic the substrate and a level set method to track the interface. Liquid Infused Surfaces reduce the drag by locking a lubricant within structured roughness to facilitate a slip velocity at the surface interface. The conceptual idea is similar to Super Hydrophobic Surfaces, which rely on a lubricant air layer, whereas liquid-infused surfaces use a preferentially wetting liquid lubricant to create a fluid-fluid interface. This slipping interface has been shown to be an effective method of passively reducing skin friction drag in turbulent flows. Details are given on the effect of the viscosity ratio between the two fluids and the dynamics of the interface on drag reduction. An attempt has been made to reconcile Super-Hydrophobic, Liquid Infused and rough wall under the same framework by correlating the drag to the wall normal velocity fluctuations.

Pembrolizumab-induced acute thrombosis: A case report.

PubMed

Kunimasa, Kei; Nishino, Kazumi; Kimura, Madoka; Inoue, Takako; Tamiya, Motohiro; Kumagai, Toru; Imamura, Fumio

2018-05-01

Acute thrombosis has not been reported in the literature so far in lung cancer patients as an immune-related adverse event (irAE) associated with PD-1 pathway inhibitors. Here, we for the first time present two NSCLC (non-small cell lung cancer) patients suffering from acute thrombosis as a pembrolizumab-induced irAE. Immediate treatment with continuous heparin infusion improved their symptoms and enabled them to continue pembrolizumab administration. Ethical approval was given by the ethics committee of Osaka International Cancer Institute and the informed consents were given by the patients. Serum D-dimer level testing, venous ultrasonography, enhanced computed tomography (CT). Continuous heparin infusion, direct oral anticoagulants (DOAC). Immediate continuous heparin infusion improved their symptoms and continuing pembrolizumab with direct oral anticoagulant successfully induced tumor shrinkage. Reinvigoration of exhausted T cells by pembrolizumab induced systemic inflammation possibly resulting in development of thrombosis. Although acute thrombosis is a rare irAE, it may lead to cessation of treatment and can be lethal.

Intravenous magnesium sulphate infusion in the management of very severe tetanus in a child: a descriptive case report.

PubMed

Puliyel, Mammen M; Pillai, Rajappan; Korula, Sophy

2009-02-01

We report a 7-year-old boy with very severe tetanus treated with continuous infusion of magnesium sulphate for the control of spasms and severe autonomic dysfunction which was refractory to deep sedation and mechanical ventilation. The infusion was not associated with any adverse effects and he made an uneventful recovery. We recommend the use of intravenous magnesium sulphate infusion as an inexpensive and highly effective modality in severe tetanus.

Nonmetabolic Complications of Continuous Subcutaneous Insulin Infusion: A Patient Survey

PubMed Central

Yemane, Nardos; Brackenridge, Anna; Pender, Siobhan

2014-01-01

Abstract Background: Little is known about the frequencies and types of nonmetabolic complications occurring in type 1 diabetes patients being treated by modern insulin pump therapy (continuous subcutaneous insulin infusion [CSII]), when recorded by standardized questionnaire rather than clinical experience. Subjects and Methods: A self-report questionnaire was completed by successive subjects with type 1 diabetes attending an insulin pump clinic, and those with a duration of CSII of ≥6 months were selected for analysis (n=92). Questions included pump manufacturer, insulin, infusion set type and duration of use, frequency of infusion set and site problems, pump malfunctions, and patient-related problems such as weight change since starting CSII. Results: Median (range) duration of CSII was 3.3 (0.5–32.0) years, and mean±SD duration of infusion set use was 3.2±0.7 (range 2–6) days. The commonest infusion set problems were kinking (64.1% of subjects) and blockage (54.3%). Blockage was associated with >3 days of use of infusion sets plus lispro insulin in the pump (relative risk [95% confidence interval], 1.71 [1.03–2.85]; P=0.07). The commonest infusion site problem was lipohypertrophy (26.1%), which occurred more often in those with long duration of CSII (4.8 [2.38–9.45] vs. 3.0 [1.50–4.25] years; P=0.01). Pump malfunction had occurred in 48% of subjects (43% in the first year of CSII), with “no delivery,” keypad, and battery problems commonly occurring. Although some patients reported weight gain (34%) and some weight loss (15%) on CSII, most patients (51%) reported no change in weight. Conclusions: Pump, infusion set, and infusion site problems remain common with CSII, even with contemporary technology. PMID:24180294

The current evidence base for the feasibility of 48-hour continuous subcutaneous infusions (CSCIs): A systematically-structured review.

PubMed

Baker, James; Dickman, Andrew; Mason, Stephen; Ellershaw, John

2018-01-01

A continuous subcutaneous infusion (CSCI) is an effective method of multiple drug administration commonly encountered in end of life care when the oral route is compromised. At present, current practice is to limit syringe driver infusion time to a maximum of 24 hours as dictated by available chemical stability data. However, the ability to deliver prescribed medication by a CSCI over 48 hours may have numerous benefits in both patient care and health service resource utilisation. To examine and present the current evidence base for the stability of 48-hour multiple-drug CSCIs in current clinical practice. A systematically-structured review following PRISMA guidelines. Three electronic databases and the grey literature were searched with no time limits. Empirical studies reporting data on the chemical stability of continuous subcutaneous infusions or solutions stored in polypropylene syringes were included. Twenty-one empirical studies were included in this review reporting chemical compatibility and stability of 32 discrete combinations of twenty-four drugs tested at a variety of different drug concentrations. The majority of combinations reported were assessed as being chemically compatible. The greatest risk of clinically significant chemical degradation was observed with midazolam. Only one study reported the microbiological stability of the solution examined. There is currently limited evidence for the physical, chemical and microbiological stability of solutions for continuous subcutaneous infusion over a period of 48 hours. More stability data is required before the use of 48-hour CSCIs can be evaluated for use within clinical practice.

Effect of mode of hydrocortisone administration on glycemic control in patients with septic shock: a prospective randomized trial.

PubMed

Loisa, Pekka; Parviainen, Ilkka; Tenhunen, Jyrki; Hovilehto, Seppo; Ruokonen, Esko

2007-01-01

Low-dose hydrocortisone treatment is widely accepted therapy for the treatment of vasopressor-dependent septic shock. The question of whether corticosteroids should be given to septic shock patients by continuous or by bolus infusion is still unanswered. Hydrocortisone induces hyperglycemia and it is possible that continuous hydrocortisone infusion would reduce the fluctuations in blood glucose levels and that tight blood glucose control could be better achieved with this approach. In this prospective randomized study, we compared the blood glucose profiles, insulin requirements, amount of nursing workload needed, and shock reversal in 48 septic shock patients who received hydrocortisone treatment either by bolus or by continuous infusion with equivalent dose (200 mg/day). Duration of hydrocortisone treatment was five days. The mean blood glucose levels were similar in the two groups, but the number of hyperglycemic episodes was significantly higher in those patients who received bolus therapy (15.7 +/- 8.5 versus 10.5 +/- 8.6 episodes per patient, p = 0.039). Also, more changes in insulin infusion rate were needed to maintain strict normoglycemia in the bolus group (4.7 +/- 2.2 versus 3.4 +/- 1.9 adjustments per patient per day, p = 0.038). Hypoglycemic episodes were rare in both groups. No difference was seen in shock reversal. Strict normoglycemia is more easily achieved if the hydrocortisone therapy is given to septic shock patients by continuous infusion. This approach also reduces nursing workload needed to maintain tight blood glucose control.

Continuous subcutaneous infusion of hyoscine butylbromide reduces secretions in patients with gastrointestinal obstruction.

PubMed

De Conno, F; Caraceni, A; Zecca, E; Spoldi, E; Ventafridda, V

1991-11-01

We describe the use of hyoscine butylbromide as a subcutaneous infusion in 3 patients with inoperable malignant bowel obstruction. An objective reduction of drainage from the gastrointestinal tract was observed with the hyoscine butylbromide infusion (60-120 mg/day). We suggest that this effect can be useful in the palliative treatment of vomiting in inoperable bowel obstruction.

Coronary artery bypass grafting in a patient with hemophilia B: continuous recombinant factor IX infusion as per the Japanese guidelines for replacement therapy.

PubMed

Suzuki, Tomoyuki; Kawamoto, Shunsuke; Kumagai, Kiichiro; Adachi, Osamu; Kanda, Keisuke; Ishikawa, Masaaki; Okitsu, Yoko; Harigae, Hideo; Kurosawa, Shin; Saiki, Yoshikatsu

2016-08-01

We herein report our experience of successfully managing the hemostatic system by controlling serum factor IX levels throughout the perioperative period in a patient with hemophilia B. Coronary artery bypass grafting with cardiopulmonary bypass was planned for a 52-year-old man with moderate severity of hemophilia B. During surgery, recombinant factor IX (rFIX; BeneFIX(®) Pfizer Japan inc., Tokyo, Japan) was administered by bolus infusion followed by continuous infusion as per the guidelines of the Japanese Society on Thrombosis and Hemostasis. The operative course was uneventful without any considerable bleeding or complications.

Comparison of intraoperative behavioral and hormonal responses to noxious stimuli between mares sedated with caudal epidural detomidine hydrochloride or a continuous intravenous infusion of detomidine hydrochloride for standing laparoscopic ovariectomy.

PubMed

Virgin, Joanna; Hendrickson, Dean; Wallis, Ty; Rao, Sangeeta

2010-08-01

To compare the presence or absence of pain, pain-related behavioral responses, and hormonal responses to noxious stimuli during standing laparoscopic ovariectomy in mares sedated with continuous intravenous (IV) detomidine infusion and caudal epidural detomidine. A double blind prospective study. Mares (n=12) Mares were divided into 2 treatment groups; 6 were sedated using continuous IV detomidine infusion and 6 were sedated with caudal epidural detomidine. All mares received IV xylazine (0.33 mg/kg) and butorphanol tartrate (5 mg) premedication before detomidine administration. Venous blood samples were taken to assess serum cortisol levels in each mare at 4 time points: a baseline cortisol measurement after the mares' arrival to the clinic, 10 minutes before surgery, at the removal of the 2nd ovary, and 10 minutes postsurgery. Two surgeons performed bilateral ovariectomy and at 8 time points involving surgical manipulations, noted the presence or absence of pain (yes/no) and scored the patient's response on a 10 cm visual analogue scale (VAS) for pain assessment with 0 indicating no pain responses and 10 cm indicating pain so severe that the mare required additional sedation or analgesia to complete the procedure. Each mare was also assigned a VAS score by each surgeon for the overall satisfaction of analgesia during the entire procedure. Serum cortisol levels between the 2 detomidine administration groups differed significantly at the baseline (precortisol) measurement but not at the 3 remaining time points. Seven of the procedures within the surgeries did not differ significantly in VAS scores between the 2 groups. The initial grasp of the left ovary (the 1st ovary) in the continuous infusion group had a significantly higher (P=.05) median VAS score compared with the caudal epidural group. Mares sedated with a continuous IV infusion of detomidine have similar hormonal and behavioral responses to painful stimuli during standing laparoscopic ovariectomy as mares sedated with caudal epidural detomidine. Sedation using a continuous IV infusion of detomidine can be used for laparoscopic ovariectomy in mares.

Does contemporary vancomycin dosing achieve therapeutic targets in a heterogeneous clinical cohort of critically ill patients? Data from the multinational DALI study

PubMed Central

2014-01-01

Introduction The objective of this study was to describe the pharmacokinetics of vancomycin in ICU patients and to examine whether contemporary antibiotic dosing results in concentrations that have been associated with favourable response. Methods The Defining Antibiotic Levels in Intensive Care (DALI) study was a prospective, multicentre pharmacokinetic point-prevalence study. Antibiotic dosing was as per the treating clinician either by intermittent bolus or continuous infusion. Target trough concentration was defined as ≥15 mg/L and target pharmacodynamic index was defined as an area under the concentration-time curve over a 24-hour period divided by the minimum inhibitory concentration of the suspected bacteria (AUC0–24/MIC ratio) >400 (assuming MIC ≤1 mg/L). Results Data of 42 patients from 26 ICUs were eligible for analysis. A total of 24 patients received vancomycin by continuous infusion (57%). Daily dosage of vancomycin was 27 mg/kg (interquartile range (IQR) 18 to 32), and not different between patients receiving intermittent or continuous infusion. Trough concentrations were highly variable (median 27, IQR 8 to 23 mg/L). Target trough concentrations were achieved in 57% of patients, but more frequently in patients receiving continuous infusion (71% versus 39%; P = 0.038). Also the target AUC0–24/MIC ratio was reached more frequently in patients receiving continuous infusion (88% versus 50%; P = 0.008). Multivariable logistic regression analysis with adjustment by the propensity score could not confirm continuous infusion as an independent predictor of an AUC0–24/MIC >400 (odds ratio (OR) 1.65, 95% confidence interval (CI) 0.2 to 12.0) or a Cmin ≥15 mg/L (OR 1.8, 95% CI 0.4 to 8.5). Conclusions This study demonstrated large interindividual variability in vancomycin pharmacokinetic and pharmacodynamic target attainment in ICU patients. These data suggests that a re-evaluation of current vancomycin dosing recommendations in critically ill patients is needed to more rapidly and consistently achieve sufficient vancomycin exposure. PMID:24887569

Induration at Injection or Infusion Site May Reduce Bioavailability of Parenteral Phenobarbital Administration.

PubMed

Nakayama, Hirokazu; Echizen, Hirotoshi; Ogawa, Ryuichi; Akabane, Atsuya; Kato, Toshiaki; Orii, Takao

2017-06-01

Phenobarbital is well tolerated and effective for controlling agitation or preventing convulsion at the end of life. No information is available concerning parenteral bioavailability of phenobarbital when induration develops at the injection or infusion site. We investigated whether induration at injection or infusion site is related to phenobarbital bioavailability via parenteral routes of continuous subcutaneous infusion and intermittent subcutaneous or intramuscular injection. A retrospective analysis was conducted on the medical data obtained from 18 patients who received chronic subcutaneous or intramuscular injections of phenobarbital for the prevention of convulsions and underwent plasma concentration monitoring of the drug. Patients whose concomitant medications were altered during the observation periods were excluded from the analysis. Comparisons were performed for concentration/dose (C/D) ratios obtained from patients with induration at injection or infusion sites (induration group, n = 6) and those without induration (noninduration group, n = 12). P < 0.05 was considered statistically significant. The induration group showed significantly reduced C/D ratio compared with the noninduration group [median (range): 0.131 (0.114-0.334) versus 0.219 (0.180-0.322) d/L, P < 0.05). Assuming that systemic clearance was constant in our patients, changes in the C/D ratio would have contributed to 40% (median) reduction in bioavailability of the drug from the injection or infusion site. Our data suggest that absolute bioavailability of phenobarbital may be reduced when induration develops at the injection or infusion site in patients treated parenterally by continuous subcutaneous infusion or intramuscular injection.

Continuous bilateral thoracic paravertebral blockade for analgesia after cardiac surgery: a randomised, controlled trial.

PubMed

Lockwood, Geoff G; Cabreros, Leilani; Banach, Dorota; Punjabi, Prakash P

2017-10-01

Continuous bilateral thoracic paravertebral blockade has been used for analgesia after cardiac surgery, but its efficacy has never been formally tested. Fifty adult patients were enrolled in a double-blind, randomised, controlled study of continuous bilateral thoracic paravertebral infusion of 0.5% lidocaine (1 mg.kg -1 .hr -1 ) for analgesia after coronary surgery. Control patients received a subcutaneous infusion of lidocaine at the same rate through catheters inserted at the same locations as the study group. The primary outcome was morphine consumption at 48 hours using patient-controlled analgesia (PCA). Secondary outcomes included pain, respiratory function, nausea and vomiting. Serum lidocaine concentrations were measured on the first two post-operative days. There was no difference in morphine consumption or in any other outcome measure between the groups. Serum lidocaine concentrations increased during the study, with a maximum of 5.9 mg.l -1 . There were no adverse events as a consequence of the study. Bilateral paravertebral infusion of lidocaine confers no advantage over systemic lidocaine infusion after cardiac surgery. ISRCTN13424423 ( https://www.isrctn.com ).

The U.K. service level audit of insulin pump therapy in adults.

PubMed

White, H D; Goenka, N; Furlong, N J; Saunders, S; Morrison, G; Langridge, P; Paul, P; Ghatak, A; Weston, P J

2014-04-01

The National Institute for Health and Clinical Excellence (NICE) published guidelines for the use of continuous subcutaneous insulin infusion in 2008 (technology appraisal 151). The first U.K.-wide insulin pump audit took place in 2012 with the aim of determining adherence to the guidance issued in NICE technology appraisal 151. The results of the adult service level audit are reported here. All centres providing continuous subcutaneous insulin infusion services to adults with diabetes in the U.K. were invited to participate. Audit metrics were aligned to technology appraisal 151. Data entry took place online using a DiabetesE formatted data collection tool. One hundred and eighty-three centres were identified as delivering adult continuous subcutaneous insulin infusion services in the U.K., of which 178 (97.3%) participated in the audit. At the time of the audit, 13 428 adults were using insulin pump therapy, giving an estimated prevalence of use of 6%. Ninety-three per cent of centres did not report any barriers in obtaining funding for patients who fulfilled NICE criteria. The mean number of consultant programmed activities dedicated to continuous subcutaneous insulin infusion services was 0.96 (range 0-8), mean whole-time equivalent diabetes specialist nurses was 0.62 (range 0-3) and mean whole-time equivalent dietitian services was 0.3 (range 0-2), of which 39, 61 and 60%, respectively, were not formally funded. The prevalence of continuous subcutaneous insulin infusion use in the U.K. falls well below the expectation of NICE (15-20%) and that of other European countries (> 15%) and the U.S.A. (40%). This may be attributable, in part, to lack of healthcare professional time needed for identification and training of new pump therapy users. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

UK service level audit of insulin pump therapy in paediatrics.

PubMed

Ghatak, A; Paul, P; Hawcutt, D B; White, H D; Furlong, N J; Saunders, S; Morrison, G; Langridge, P; Weston, P J

2015-12-01

To conduct an audit of insulin pump therapy in the UK after the issue of guidelines for the use of continuous subcutaneous insulin infusion by NICE in 2008 (Technology Appraisal 151). All centres in the UK, providing pump services to children and young people were invited to participate in an online audit. Audit metrics were aligned to NICE Technology Appraisal 151 and an electronic data collection tool was used. Of the 176 UK centres identified as providing pump services, 166 (94.3%) participated in the study. A total of 5094 children and young people were identified as using continuous subcutaneous insulin infusion (19% of all paediatric patients with Type 1 diabetes), with a median (range) of 16.9 (0.67-69.4)% per centre. Units had a median of 0.58 consultant sessions, 0.43 full-time equivalent diabetic specialist nurses, and 0.1 full-time equivalent dieticians delivering the pump service. The majority of this time was not formally funded. Families could access 24-h clinical and technical support (83% units), although the delivery varied between consultant, diabetic specialist nurse and company representatives. Only 53% of units ran, or accessed, structured education programmes for continuous subcutaneous insulin infusion use. Most units (86%) allowed continuous subcutaneous insulin infusion use for paediatric inpatients, but only 56% had written guidelines for this scenario. Nine percent of units had encountered funding refusal for a patient fulfilling NICE (Technology Appraisal 151) criteria. The number of children and young people on continuous subcutaneous insulin infusion therapy is consistent with numbers estimated by NICE. There is a worrying lack of funded healthcare professional time. The audit also identified gaps in the provision of structured education and absence of written inpatient guidelines. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

Continuous infusion or bolus injection of loop diuretics for patients admitted for severe acute heart failure: is one strategy better than the other?

PubMed

Caetano, Francisca; Mota, Paula; Almeida, Inês; Fernandes, Andreia; Botelho, Ana; Leitão Marques, António

2015-02-01

Intravenous loop diuretics are an essential part of acute heart failure management; however, data to guide their use is sparse. Our aim was to compare continuous intravenous infusion of loop diuretics with intravenous bolus administration in terms of efficacy and adverse events in patients admitted with severe acute heart failure. Over a period of three years, 110 patients were admitted to our cardiac intensive care unit with acute heart failure. Clinical, laboratory and prognostic parameters were compared according to the diuretic strategy used and mortality and readmission for acute heart failure during follow-up were analyzed. Previous medical history was similar in the two groups. At admission, the continuous infusion group met criteria for worse prognosis: lower systolic blood pressure (p=0.011), more severe renal injury (p=0.008), lower left ventricular ejection fraction (p=0.016) and higher incidence of restrictive pattern of diastolic dysfunction (p=0.032). They were more often treated with vasopressors (p=0.003), inotropes (p=0.010), renal support therapy (p=0.003) and non-invasive ventilation (p<0.001). They had longer hospitalizations (p=0.014) and a higher incidence of cardiorenal syndrome (p=0.009); however, at discharge, there were no differences in renal function between the groups. In-hospital mortality was similar, and during follow-up there were no differences in mortality or readmission for acute heart failure. Continuous infusion was preferred in patients presenting with worse clinical status, in whom renal dysfunction was transiently worse. However, in-hospital mortality and creatinine at discharge were similar. Continuous infusion thus appears to counteract the initial dire prognosis of more unstable patients. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Severe hypertriglyceridaemia in Type 2 diabetes mellitus: beneficial effect of continuous insulin infusion.

PubMed

Henderson, S R; Maitland, R; Mustafa, O G; Miell, J; Crook, M A; Kottegoda, S R

2013-04-01

Severe hypertriglyceridaemia is a recognized complication of Type 2 diabetes mellitus (T2DM); however, there is no consensus on acute management despite the significant risk of developing associated complications such as acute pancreatitis and hyperviscosity syndrome. To identify the association between hyperglycaemia and severe hypertriglyceridaemia in patients with T2DM and assess the effect of continuous insulin infusion therapy on serum triglyceride (TG) concentrations and report any adverse events associated with this therapeutic approach. Retrospective review of case records. Patients with uncontrolled hyperglycaemia and severe hypertriglyceridaemia (serum TG > 15 mmol/l) treated with continuous intravenous insulin infusion between October 2008 and September 2009 were retrospectively evaluated (n = 15). Details recorded included demographics, admission details, lipid profiles, glycaemic control, serum amylase and adverse events. Patients receiving treatment-dose unfractionated heparin infusion were excluded. Severe hypertriglyceridaemia is associated with hyperglycaemia in our heterogeneous group of patients with T2DM presenting with new-onset diabetes or established disease on pre-existing insulin or oral hypoglycaemic agents. Administration of continuous exogenous insulin not only achieved normoglycaemia but also dramatically corrected severe hypertriglyceridaemia in all patients (P = 0.001). The administration of continuous insulin in patients with T2DM with severe hypertriglyceridaemia is a simple and safe method of significantly reducing the immediate risk associated with this metabolic complication and should be considered in any T2DM patient presenting with severe hypertriglyceridaemia and hyperglycaemia.

Plasma concentrations of midazolam during continuous subcutaneous administration in palliative care.

PubMed

Bleasel, M D; Peterson, G M; Dunne, P F

1994-01-01

We have investigated the steady-state plasma concentrations of midazolam during continuous subcutaneous administration in palliative care. Using a sensitive gas chromatography with electron capture detector assay, plasma concentrations of midazolam were measured in 11 patients (median age 68 years; range 47-82 years; six females) receiving the drug by continuous subcutaneous infusion (median rate 20 mg/day; range 10-60 mg/day). While not significant, the infusion rate tended to decrease with increasing age of the patient (Spearman's p = -0.51; p = 0.11). The steady-state plasma concentration range was 10-147 ng/ml, with a median of 30 ng/ml. Infusion rates and plasma concentrations of midazolam were correlated (Spearman's p = 0.71; p < 0.05). No other significant relationships were found between plasma concentrations and the variables of age, sex and liver function.

Continuous subcutaneous infusion of lidocaine for persistent hiccup in advanced cancer.

PubMed

Kaneishi, Keisuke; Kawabata, Masahiro

2013-03-01

Persistent hiccup can cause anorexia, weight loss, disabling sleep deprivation, anxiety, and depression. Therefore, relief of persistent hiccup is important for advanced cancer patients and their family. Most reports on this condition are case series reports advocating the use of baclofen, haloperidol, gabapentin, and midazolam. However, these medications are occasionally ineffective or accompanied by intolerable side effects. The sodium channel blocker lidocaine has been shown to be effective in treating a variety of disorders thought to involve neuropathic mechanisms. Intravenous administration of lidocaine is common but efficacy has also been reported for subcutaneous infusion. In advanced cancer patients, subcutaneous infusion is easy, advantageous, and accompanied by less discomfort. We report a case of severe and sustained hiccup caused by gastric cancer that was successfully treated with a continuous subcutaneous infusion of lidocaine (480 mg (24 ml)/day) without severe side effects.

Intravenous labetolol in treating hypertensive crisis following dexmedetomidine infusion for procedural sedation.

PubMed

Muthiah, Thilaka; Moni, Amarnath; Mathews, Lailu; Balaji, Sudarshan

2016-03-01

Dexmedetomidine is widely used for procedural sedation because of its unique combination of sedation, analgesia, and anxiolysis with minimal respiratory depression. Transient hypertension has been reported during the use of dexmedetomidine which is usually benign and is taken over by the hypotensive response on continuing the infusion. We report a case of hypertensive crisis following dexmedetomidine infusion used for procedural sedation, necessitating discontinuation of the infusion and treatment of hypertension. The dilemmas involved in treating hypertension caused by dexmedetomidine are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of programmed intermittent epidural boluses and continuous epidural infusion on labor analgesia and obstetric outcomes: a randomized controlled trial.

PubMed

Ferrer, Leopoldo E; Romero, David J; Vásquez, Oscar I; Matute, Ednna C; Van de Velde, Marc

2017-11-01

Continuous epidural infusion and programmed intermittent epidural boluses are analgesic techniques routinely used for pain relief in laboring women. We aimed to assess both techniques and compare them with respect to labor analgesia and obstetric outcomes. After Institutional Review Board approval, 132 laboring women aged between 18 and 45 years were randomized to epidural analgesia of 10 mL of a mixture of 0.1% bupivacaine plus 2 µg/mL of fentanyl either by programmed intermittent boluses or continuous infusion (66 per group). Primary outcome was quality of analgesia. Secondary outcomes were duration of labor, total drug dose used, maternal satisfaction, sensory level, motor block level, presence of unilateral motor block, hemodynamics, side effects, mode of delivery, and newborn outcome. Patients in the programmed intermittent epidural boluses group received statistically less drug dose than those with continuous epidural infusion (24.9 vs 34.4 mL bupivacaine; P = 0.01). There was no difference between groups regarding pain control, characteristics of block, hemodynamics, side effects, and Apgar scores. Our study evidenced a lower anesthetic consumption in the programmed intermittent boluses group with similar labor analgesic control, and obstetric and newborn outcomes in both groups.

Insulin Infusion Set: The Achilles Heel of Continuous Subcutaneous Insulin Infusion

PubMed Central

Heinemann, Lutz; Krinelke, Lars

2012-01-01

Continuous subcutaneous insulin infusion from an insulin pump depends on reliable transfer of the pumped insulin to the subcutaneous insulin depot by means of an insulin infusion set (IIS). Despite their widespread use, the published knowledge about IISs and related issues regarding the impact of placement and wear time on insulin absorption/insulin action is relatively small. We also have to acknowledge that our knowledge is limited with regard to how often patients encounter issues with IISs. Reading pump wearer blogs, for instance, suggests that these are a frequent source of trouble. There are no prospective clinical studies available on current IIS and insulin formulations that provide representative data on the type and frequency of issues with infusion sets. The introduction of new IISs and patch pumps may foster a reassessment of available products and of patient problems related to their use. The aim of this review is to summarize the current knowledge and recommendations about IISs and to highlight potential directions of IIS development in order to make insulin absorption safer and more efficient. PMID:22920824

Investigation of dynamic SPECT measurements of the arterial input function in human subjects using simulation, phantom and human studies

NASA Astrophysics Data System (ADS)

Winant, Celeste D.; Aparici, Carina Mari; Zelnik, Yuval R.; Reutter, Bryan W.; Sitek, Arkadiusz; Bacharach, Stephen L.; Gullberg, Grant T.

2012-01-01

Computer simulations, a phantom study and a human study were performed to determine whether a slowly rotating single-photon computed emission tomography (SPECT) system could provide accurate arterial input functions for quantification of myocardial perfusion imaging using kinetic models. The errors induced by data inconsistency associated with imaging with slow camera rotation during tracer injection were evaluated with an approach called SPECT/P (dynamic SPECT from positron emission tomography (PET)) and SPECT/D (dynamic SPECT from database of SPECT phantom projections). SPECT/P simulated SPECT-like dynamic projections using reprojections of reconstructed dynamic 94Tc-methoxyisobutylisonitrile (94Tc-MIBI) PET images acquired in three human subjects (1 min infusion). This approach was used to evaluate the accuracy of estimating myocardial wash-in rate parameters K1 for rotation speeds providing 180° of projection data every 27 or 54 s. Blood input and myocardium tissue time-activity curves (TACs) were estimated using spatiotemporal splines. These were fit to a one-compartment perfusion model to obtain wash-in rate parameters K1. For the second method (SPECT/D), an anthropomorphic cardiac torso phantom was used to create real SPECT dynamic projection data of a tracer distribution derived from 94Tc-MIBI PET scans in the blood pool, myocardium, liver and background. This method introduced attenuation, collimation and scatter into the modeling of dynamic SPECT projections. Both approaches were used to evaluate the accuracy of estimating myocardial wash-in parameters for rotation speeds providing 180° of projection data every 27 and 54 s. Dynamic cardiac SPECT was also performed in a human subject at rest using a hybrid SPECT/CT scanner. Dynamic measurements of 99mTc-tetrofosmin in the myocardium were obtained using an infusion time of 2 min. Blood input, myocardium tissue and liver TACs were estimated using the same spatiotemporal splines. The spatiotemporal maximum-likelihood expectation-maximization (4D ML-EM) reconstructions gave more accurate reconstructions than did standard frame-by-frame static 3D ML-EM reconstructions. The SPECT/P results showed that 4D ML-EM reconstruction gave higher and more accurate estimates of K1 than did 3D ML-EM, yielding anywhere from a 44% underestimation to 24% overestimation for the three patients. The SPECT/D results showed that 4D ML-EM reconstruction gave an overestimation of 28% and 3D ML-EM gave an underestimation of 1% for K1. For the patient study the 4D ML-EM reconstruction provided continuous images as a function of time of the concentration in both ventricular cavities and myocardium during the 2 min infusion. It is demonstrated that a 2 min infusion with a two-headed SPECT system rotating 180° every 54 s can produce measurements of blood pool and myocardial TACs, though the SPECT simulation studies showed that one must sample at least every 30 s to capture a 1 min infusion input function.

Small intestinal digestion of raw cornstarch in cattle consuming a soybean hull-based diet is improved by duodenal casein infusion.

PubMed

Brake, D W; Titgemeyer, E C; Bailey, E A; Anderson, D E

2014-09-01

Six duodenally and ileally cannulated steers were used in 3 sequential studies to measure 1) basal nutrient flows from a soybean hull-based diet, 2) small intestinal digestibility of raw cornstarch continuously infused into the duodenum, and 3) responses of small intestinal starch digestion to duodenal infusion of 200 or 400 g/d casein. Our objective was to evaluate responses in small intestinal starch digestion in cattle over time and to measure responses in small intestinal starch digestion to increasing amounts of MP. On average, cattle consumed 3.7 kg/d DM, 68 g/d dietary N, and 70 g/d dietary starch. Starch flow to the duodenum was small (38 g/d), and N flow was 91 g/d. Small intestinal digestibility of duodenal N was 57%, and small intestinal digestion of duodenal starch flow was extensive (92%). Small intestinal starch digestibility was 34% when 1.5 kg/d raw cornstarch was continuously infused into the duodenum. Subsequently, cattle were placed in 1 of 2 replicated Latin squares that were balanced for carryover effects to determine response to casein infusions and time required for adaptation. Duodenal infusion of casein linearly increased (P ≤ 0.05) small intestinal starch digestibility, and small intestinal starch digestion adapted to infusion of casein in 6 d. Ethanol-soluble starch and unpolymerized glucose flowing to the ileum increased linearly (P ≤ 0.05) with increasing infusion of casein. Plasma cholecystokinin was not affected by casein infusion, but circulating levels of glucose were increased by casein supplementation (P ≤ 0.05). Responses in small intestinal starch digestion in cattle adapted to casein within 6 d, and increases in duodenal supply of casein up to 400 g/d increased small intestinal starch digestion in cattle.

Single-shot pectoral plane (PECs I and PECs II) blocks versus continuous local anaesthetic infusion analgesia or both after non-ambulatory breast-cancer surgery: a prospective, randomised, double-blind trial.

PubMed

O'Scanaill, P; Keane, S; Wall, V; Flood, G; Buggy, D J

2018-04-01

Pectoral plane blocks (PECs) are increasingly used in analgesia for patients undergoing breast surgery, and were recently found to be at least equivalent to single-shot paravertebral anaesthesia. However, there are no data comparing PECs with the popular practice of continuous local anaesthetic wound infusion (LA infusion) analgesia for breast surgery. Therefore, we compared the efficacy and safety of PECs blocks with LA infusion, or a combination of both in patients undergoing non-ambulatory breast-cancer surgery. This single-centre, prospective, randomised, double-blind trial analysed 45 women to receive either PECs blocks [levobupivacaine 0.25%, 10 ml PECs I and levobupivacaine 0.25%, 20 ml PECs II (PECs group); LA infusion catheter (levobupivacaine 0.1% at 10 ml h -1 for 24 h (LA infusion group); or both (PECs and LA infusion)]. The primary outcome measure was area under the curve of the pain verbal rating score whilst moving vs time (AUC) over 24 h. Secondary outcomes included total opioid consumption at 24 h. AUC moving was mean (SD) 71 (34) mm h -1 vs 58 (41) vs 23 (20) in PECs, LA infusion, and both, respectively; P=0.002. AUC at rest was also significantly lower in patients receiving both. The total 24 h opioid consumption [median (25-75%)] was 14 mg (9-26) vs 11 (8-24) vs 9 (5-11); P=0.4. No adverse events were observed. The combination of both pre-incisional PECs blocks and postoperative LA infusion provides better analgesia over 24 h than either technique alone after non-ambulatory breast-cancer surgery. NCT 03024697. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Advancing Novel Anesthetics: Pharmacodynamic and Pharmacokinetic Studies of Cyclopropyl-Methoxycarbonyl Metomidate in Dogs

PubMed Central

Campagna, Jason A.; Pojasek, Kevin; Grayzel, David; Randle, John; Raines, Douglas E.

2014-01-01

Background Cyclopropyl-methoxycarbonyl metomidate (CPMM, also known as ABP-700) is a second-generation “soft” (i.e., metabolically-labile) etomidate analogue. The purpose of these studies was to characterize CPMM's pharmacology in beagle dogs in preparation for potential first in human phase 1 clinical trials. Methods CPMM's and etomidate's hypnotic activity and duration of action were assessed using loss of righting reflex and anesthesia score assays in three or four dogs. Their pharmacokinetics were defined after single bolus administration and single bolus followed by 2-h infusion. Adrenocortical recovery times after single bolus followed by 2-h infusion of CPMM, propofol, etomidate, and vehicle were measured using an adrenocorticotropic hormone stimulation test. Results Compared to etomidate, CPMM was half as potent as a hypnotic (ED50 ~ 0.8 mg/kg), more rapidly metabolized, and had a shorter duration of sedative-hypnotic action. Recovery times after CPMM administration were also independent of infusion duration. After hypnotic infusion, adrenocorticotropic hormone-stimulated plasma cortisol concentrations were 4- to 27-fold higher in dogs that received CPMM versus etomidate. Adrenocortical recovery was faster in dogs after CPMM infusion versus etomidate infusion (half-time: 215 min vs. 1623 min, respectively). Adrenocortical responsiveness assessed 90 min after CPMM infusion was not significantly different from that after propofol infusion. Conclusion Our studies in dogs confirm that CPMM has hypnotic and adrenocortical recovery profiles that are superior than those of etomidate, supporting the continued development of CPMM as a clinical sedative-hypnotic to be used as a single bolus and by continuous infusion to induce and maintain general anesthesia or procedural sedation. PMID:25170571

Continuous infusion or bolus injection of loop diuretics for congestive heart failure?

PubMed

Zepeda, Patricio; Rain, Carmen; Sepúlveda, Paola

2016-04-22

Loop diuretics are widely used in acute heart failure. However, there is controversy about the superiority of continuous infusion over bolus administration. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified four systematic reviews including 11 pertinent randomized controlled trials overall. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded continuous administration of loop diuretics probably reduces mortality and length of stay compared to intermittent administration in patients with acute heart failure.

The current evidence base for the feasibility of 48-hour continuous subcutaneous infusions (CSCIs): A systematically-structured review

PubMed Central

Dickman, Andrew; Mason, Stephen; Ellershaw, John

2018-01-01

Background A continuous subcutaneous infusion (CSCI) is an effective method of multiple drug administration commonly encountered in end of life care when the oral route is compromised. At present, current practice is to limit syringe driver infusion time to a maximum of 24 hours as dictated by available chemical stability data. However, the ability to deliver prescribed medication by a CSCI over 48 hours may have numerous benefits in both patient care and health service resource utilisation. Aim To examine and present the current evidence base for the stability of 48-hour multiple-drug CSCIs in current clinical practice. Design A systematically-structured review following PRISMA guidelines. Data sources Three electronic databases and the grey literature were searched with no time limits. Empirical studies reporting data on the chemical stability of continuous subcutaneous infusions or solutions stored in polypropylene syringes were included. Results Twenty-one empirical studies were included in this review reporting chemical compatibility and stability of 32 discrete combinations of twenty-four drugs tested at a variety of different drug concentrations. The majority of combinations reported were assessed as being chemically compatible. The greatest risk of clinically significant chemical degradation was observed with midazolam. Only one study reported the microbiological stability of the solution examined. Conclusions There is currently limited evidence for the physical, chemical and microbiological stability of solutions for continuous subcutaneous infusion over a period of 48 hours. More stability data is required before the use of 48-hour CSCIs can be evaluated for use within clinical practice. PMID:29538455

Type of homogenization and fat loss during continuous infusion of human milk.

PubMed

García-Lara, Nadia Raquel; Escuder-Vieco, Diana; Alonso Díaz, Clara; Vázquez Román, Sara; De la Cruz-Bértolo, Javier; Pallás-Alonso, Carmen Rosa

2014-11-01

Substantial fat loss may occur during continuous feeding of human milk (HM). A decrease of fat loss has been described following homogenization. Well-established methods of homogenization of HM for routine use in the neonatal intensive care unit (NICU) would be desirable. We compared the loss of fat based on the use of 3 different methods for homogenizing thawed HM during continuous feeding. Sixteen frozen donor HM samples were thawed, homogenized with ultrasound and separated into 3 aliquots ("baseline agitation," "hourly agitation," and "ultrasound"), and then frozen for 48 hours. Aliquots were thawed again and a baseline agitation was applied. Subsequently, aliquots baseline agitation and hourly agitation were drawn into a syringe, while ultrasound was applied to aliquot ultrasound before it was drawn into a syringe. The syringes were loaded into a pump (2 mL/h; 4 hours). At hourly intervals the hourly agitation infusion was stopped, the syringe was disconnected and gently shaken. During infusion, samples from the 3 groups were collected hourly for analysis of fat and caloric content. The 3 groups of homogenization showed similar fat content at the beginning of the infusion. For fat, mean (SD) hourly changes of -0.03 (0.01), -0.09 (0.01), and -0.09 (0.01) g/dL were observed for the hourly agitation, baseline agitation, and ultrasound groups, respectively. The decrease was smaller for the hourly agitation group (P < .001). When thawed HM is continuously infused, a smaller fat loss is observed when syringes are agitated hourly versus when ultrasound or a baseline homogenization is used. © The Author(s) 2014.

SMARTDIAB: a communication and information technology approach for the intelligent monitoring, management and follow-up of type 1 diabetes patients.

PubMed

Mougiakakou, Stavroula G; Bartsocas, Christos S; Bozas, Evangelos; Chaniotakis, Nikos; Iliopoulou, Dimitra; Kouris, Ioannis; Pavlopoulos, Sotiris; Prountzou, Aikaterini; Skevofilakas, Marios; Tsoukalis, Alexandre; Varotsis, Kostas; Vazeou, Andrianni; Zarkogianni, Konstantia; Nikita, Konstantina S

2010-05-01

SMARTDIAB is a platform designed to support the monitoring, management, and treatment of patients with type 1 diabetes mellitus (T1DM), by combining state-of-the-art approaches in the fields of database (DB) technologies, communications, simulation algorithms, and data mining. SMARTDIAB consists mainly of two units: 1) the patient unit (PU); and 2) the patient management unit (PMU), which communicate with each other for data exchange. The PMU can be accessed by the PU through the internet using devices, such as PCs/laptops with direct internet access or mobile phones via a Wi-Fi/General Packet Radio Service access network. The PU consists of an insulin pump for subcutaneous insulin infusion to the patient and a continuous glucose measurement system. The aforementioned devices running a user-friendly application gather patient's related information and transmit it to the PMU. The PMU consists of a diabetes data management system (DDMS), a decision support system (DSS) that provides risk assessment for long-term diabetes complications, and an insulin infusion advisory system (IIAS), which reside on a Web server. The DDMS can be accessed from both medical personnel and patients, with appropriate security access rights and front-end interfaces. The DDMS, apart from being used for data storage/retrieval, provides also advanced tools for the intelligent processing of the patient's data, supporting the physician in decision making, regarding the patient's treatment. The IIAS is used to close the loop between the insulin pump and the continuous glucose monitoring system, by providing the pump with the appropriate insulin infusion rate in order to keep the patient's glucose levels within predefined limits. The pilot version of the SMARTDIAB has already been implemented, while the platform's evaluation in clinical environment is being in progress.

Continuous Glucose Monitoring Enables the Detection of Losses in Infusion Set Actuation (LISAs)

PubMed Central

Howsmon, Daniel P.; Cameron, Faye; Baysal, Nihat; Ly, Trang T.; Forlenza, Gregory P.; Maahs, David M.; Buckingham, Bruce A.; Hahn, Juergen; Bequette, B. Wayne

2017-01-01

Reliable continuous glucose monitoring (CGM) enables a variety of advanced technology for the treatment of type 1 diabetes. In addition to artificial pancreas algorithms that use CGM to automate continuous subcutaneous insulin infusion (CSII), CGM can also inform fault detection algorithms that alert patients to problems in CGM or CSII. Losses in infusion set actuation (LISAs) can adversely affect clinical outcomes, resulting in hyperglycemia due to impaired insulin delivery. Prolonged hyperglycemia may lead to diabetic ketoacidosis—a serious metabolic complication in type 1 diabetes. Therefore, an algorithm for the detection of LISAs based on CGM and CSII signals was developed to improve patient safety. The LISA detection algorithm is trained retrospectively on data from 62 infusion set insertions from 20 patients. The algorithm collects glucose and insulin data, and computes relevant fault metrics over two different sliding windows; an alarm sounds when these fault metrics are exceeded. With the chosen algorithm parameters, the LISA detection strategy achieved a sensitivity of 71.8% and issued 0.28 false positives per day on the training data. Validation on two independent data sets confirmed that similar performance is seen on data that was not used for training. The developed algorithm is able to effectively alert patients to possible infusion set failures in open-loop scenarios, with limited evidence of its extension to closed-loop scenarios. PMID:28098839

Continuous Glucose Monitoring Enables the Detection of Losses in Infusion Set Actuation (LISAs).

PubMed

Howsmon, Daniel P; Cameron, Faye; Baysal, Nihat; Ly, Trang T; Forlenza, Gregory P; Maahs, David M; Buckingham, Bruce A; Hahn, Juergen; Bequette, B Wayne

2017-01-15

Reliable continuous glucose monitoring (CGM) enables a variety of advanced technology for the treatment of type 1 diabetes. In addition to artificial pancreas algorithms that use CGM to automate continuous subcutaneous insulin infusion (CSII), CGM can also inform fault detection algorithms that alert patients to problems in CGM or CSII. Losses in infusion set actuation (LISAs) can adversely affect clinical outcomes, resulting in hyperglycemia due to impaired insulin delivery. Prolonged hyperglycemia may lead to diabetic ketoacidosis-a serious metabolic complication in type 1 diabetes. Therefore, an algorithm for the detection of LISAs based on CGM and CSII signals was developed to improve patient safety. The LISA detection algorithm is trained retrospectively on data from 62 infusion set insertions from 20 patients. The algorithm collects glucose and insulin data, and computes relevant fault metrics over two different sliding windows; an alarm sounds when these fault metrics are exceeded. With the chosen algorithm parameters, the LISA detection strategy achieved a sensitivity of 71.8% and issued 0.28 false positives per day on the training data. Validation on two independent data sets confirmed that similar performance is seen on data that was not used for training. The developed algorithm is able to effectively alert patients to possible infusion set failures in open-loop scenarios, with limited evidence of its extension to closed-loop scenarios.

Absorption of subcutaneously infused insulin: influence of the basal rate pulse interval.

PubMed

Hildebrandt, P; Birch, K; Jensen, B M; Kühl, C; Brange, J

1985-01-01

Eight insulin-dependent diabetic patients were given two constant infusions (each 1 IU/h) of 125I-labeled insulin into the abdominal subcutaneous tissue for about 12 h. Insulin was infused in pulses into one side of the abdomen in 6-min intervals (by means of an Auto-Syringe pump) and in the other side of the abdomen, insulin was infused in 1-h intervals (by means of a Medix pump). The size of the subcutaneous depots was continuously measured by counting the radioactivity at the infusion sites. After starting the infusions, the two depots were built up to steady-state levels at the same time and of the same size (approximately 3 IU) and with similar absorption rates. Thus, during basal rate insulin infusion, identical insulin absorption kinetics was achieved, irrespective of a 10-fold difference in the pulse rate.

Continuous subcutaneous infusion of morphine in children with cancer.

PubMed

Miser, A W; Davis, D M; Hughes, C S; Mulne, A F; Miser, J S

1983-04-01

Seventeen children with severe pain due to malignant neoplasm were successfully treated with a subcutaneous infusion of morphine sulfate using a syringe pump. Pain relief was adequate in every case without major side effects. The median dosage required was 0.06 mg/kg/hr (range, 0.025 to 1.79 mg/kg/hr). Three patients received the subcutaneous infusion at home. No patient required an intravenous line for pain control.

Single-injection or continuous femoral nerve block for total knee arthroplasty?

PubMed

Albrecht, Eric; Morfey, Dorothea; Chan, Vincent; Gandhi, Rajiv; Koshkin, Arkadiy; Chin, Ki Jinn; Robinson, Sylvie; Frascarolo, Philippe; Brull, Richard

2014-05-01

The ideal local anesthetic regime for femoral nerve block that balances analgesia with mobility after total knee arthroplasty (TKA) remains undefined. We compared two volumes and concentrations of a fixed dose of ropivacaine for continuous femoral nerve block after TKA to a single injection femoral nerve block with ropivacaine to determine (1) time to discharge readiness; (2) early pain scores and analgesic consumption; and (3) functional outcomes, including range of motion and WOMAC scores at the time of recovery. Ninety-nine patients were allocated to one of three continuous femoral nerve block groups for this randomized, placebo-controlled, double-blind trial: a high concentration group (ropivacaine 0.2% infusion), a low concentration group (ropivacaine 0.1% infusion), or a placebo infusion group (saline 0.9% infusion). Infusions were discontinued on postoperative Day (POD) 2. The primary outcome was time to discharge readiness. Secondary outcomes included opioid consumption, pain, and functional outcomes. Ninety-three patients completed the study protocol; the study was halted early because of unanticipated changes to pain protocols at the host institution, by which time only 61% of the required number of patients had been enrolled. With the numbers available, the mean time to discharge readiness was not different between groups (high concentration group, 62 hours [95% confidence interval [CI], 51-72 hours]; low concentration group, 73 hours [95% CI, 63-83 hours]; placebo infusion group 65 hours [95% CI, 56-75 hours]; p = 0.27). Patients in the low concentration group consumed significantly less morphine during the period of infusion (POD 1, high concentration group, 56 mg [95% CI, 42-70 mg]; low concentration group, 35 mg [95% CI, 27-43 mg]; placebo infusion group, 48 mg [95% CI, 38-59 mg], p = 0.02; POD 2, high concentration group, 50 mg [95% CI, 41-60 mg]; low concentration group, 33 mg [95% CI, 24-42 mg]; placebo infusion group, 39 mg [95% CI, 30-48 mg], p = 0.04); however, there were no important differences in pain scores or opioid-related side effects with the numbers available. Likewise, there were no important differences in functional outcomes between groups. Based on this study, which was terminated prematurely before the desired sample size could be achieved, we were unable to demonstrate that varying the concentration and volume of a fixed-dose ropivacaine infusion for continuous femoral nerve block influences time to discharge readiness when compared with a conventional single-injection femoral nerve block after TKA. A low concentration of ropivacaine infusion can reduce postoperative opioid consumption but without any important differences in pain scores, side effects, or functional outcomes. These pilot data may be used to inform the statistical power of future randomized trials. Level II, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Remote and chronic access to the third cerebral ventricle of the unrestrained prepubertal rhesus monkey.

PubMed

Gay, V L; Mikuma, N; Plant, T M

1993-03-01

One channel of a commercially available standard-size three-channel fluid swivel was modified to permit continuous access to the brain of unrestrained prepubertal rhesus monkeys via a continuous length of small-bore Teflon tube originating from a swivel device on top of the animal's cage and terminating in the third cerebral ventricle. This system was employed to achieve continuous access to the third cerebroventricle in four monkeys for periods of up to 12 mo. The value of the system for studies of the neurochemical control of hypothalamic-releasing factor secretion was established by monitoring adenohypophysial responses to neurotransmitter receptor agonists infused into the third ventricle. Specifically, repetitive infusions of morphine (30 micrograms/infusion) elicited a robust train of prolactin discharges, and third ventricular administration of N-methyl-DL-aspartic acid (NMA; 20 micrograms) resulted in striking discharges of LH.

Fentanyl by continuous subcutaneous infusion for the management of cancer pain: a retrospective study.

PubMed

Watanabe, S; Pereira, J; Hanson, J; Bruera, E

1998-11-01

Twenty-two patients who received fentanyl by continuous subcutaneous infusion for treatment of cancer pain were evaluated retrospectively. No local toxicities were noted. Five patients were switched from transdermal fentanyl due to uncontrolled pain; three achieved stability, accompanied by improvement in visual analogue scores for pain. Seventeen patients were switched from other opioids due to toxicity; 10 achieved stability, with documented improvement in toxicity in seven. The median dose ratio of opioid prior to switchover (mg/day) to fentanyl at stabilization (mg/day) was 85.4 (range 65-112.5) for morphine and 23.0 (range 10.7-29.7) for hydromorphone. Of six stable patients switched from subcutaneous to transdermal fentanyl, four maintained stability. We conclude that fentanyl by continuous subcutaneous infusion is a useful alternative for cancer patients who experience uncontrolled pain while receiving transdermal fentanyl or who experience toxicity on other opioids.

Unintentional Infusion of Phenylephrine into the Epidural Space.

PubMed

Townley, Kress R; Lane, Jason; Packer, Robyn; Gupta, Rajnish K

2016-03-01

We describe a patient who received an unintentionally prolonged epidural infusion of phenylephrine. The patient experienced no major morbidity. However, this case highlights the continuing problem of wrong-route drug administration and the urgent need to adopt route-specific connections.

Pharmacokinetic Analysis of Ziconotide (SNX-111), an Intrathecal N-type Calcium Channel Blocking Analgesic, Delivered by Bolus and Infusion in the Dog

PubMed Central

Yaksh, Tony L.; de Kater, Annelies; Dean, Robin; Best, Brookie M.; Miljanich, George P.

2012-01-01

SUMMARY Background and purpose Ziconotide is a peptide that blocks N-type calcium channels and is anti-hyperalgesic after intrathecal delivery. We here characterize the spinal kinetics of intrathecal bolus and infused ziconotide in dog. Experimental approach Male beagle dogs (N = 5) were prepared with chronic intrathecal (IT) lumbar injection and cerebrospinal fluid (LCSF) sampling catheters connected to vest-mounted pumps. Each dog received: i) IT bolus ziconotide (10 µg + 1 µCi 3H-inulin), ii) IT infusion for 48 hr of ziconotide (1 µg/100 µL/hr), iii) IT infusion for 48 hr of ziconotide (5 µg/100 µL/hr), and iv) intravenous injection of ziconotide (0.1 mg/kg). After IT bolus, LCSF ziconotide and inulin showed an initial peak and biphasic (distribtution/elimination) clearance (ziconotide T1/2 α / ß = 0.14 and 1.77 hr, and inulin T1/2 α / ß = 0.16 and 3.88 hr, respectively). The LCSF: plasma ziconotide concentration ratio was 20,000: 1 at 30 min, and 30: 1 at 8 hr. IT infusion of 1 and then 5 µg/hr resulted in LCSF concentrations that peaked by 8 hr and remained stable at 343 and 1380 ng/mL, respectively, to the end of the 48-hr infusions. Terminal elimination T1/2 after termination of continuous infusion was 2.47 hr. Ziconotide LCSF: cisternal CSF: plasma concentration ratios after infusion of 1 µg/hr and 5 µg/hr were 1: 0.017: 0.001 and 1: 0.015: 0.003, respectively. IT infusion of ziconotide at 1 µg/hr inhibited thermal skin twitch by 24 hr, and produced modest trembling, ataxia, and decreased arousal. Effects continued through the 48-hr infusion period, increased in magnitude during the subsequent 5 µg/hr infusion periods, and disappeared after drug clearance. Conclusions and Implications After intrathecal bolus or infusion, ziconotide displays linear kinetics that are consistent with a hydrophilic molecule of approximately 2500 Da that is cleared slightly more rapidly than inulin from the LCSF. Behavioral effects were dose dependent and reversible. PMID:22748108

Two phase I, pharmacokinetic, and pharmacodynamic studies of DFP-10917, a novel nucleoside analog with 14-day and 7-day continuous infusion schedules.

PubMed

Sankhala, Kamalesh; Takimoto, Chris H; Mita, Alain C; Xiong, Henry; Rodón, Jordi; Mehrvarz Sarshekeh, Amir; Burns, K; Iizuka, Kenzo; Kopetz, Scott

2018-04-18

Purpose DFP-10917 is a novel deoxycytidine analog with a unique mechanism of action. Brief exposure to high concentrations of DFP-10917 inhibits DNA polymerase resulting in S-phase arrest, while prolonged exposure to DFP-10917 at low concentration causes DNA fragmentation, G2/M-phase arrest, and apoptosis. DFP-10917 demonstrated activity in tumor xenografts resistant to other deoxycytidine analogs. Experimental design Two phase I studies assessed the safety, pharmacokinetic, pharmacodynamic and preliminary efficacy of DFP-10917. Patients with refractory solid tumors received DFP-10917 continuous infusion 14-day on/7-day off and 7-day on/7-day off. Enrollment required age > 18 years, ECOG Performance Status 0-2 and adequate organ function. Results 29 patients were dosed in both studies. In 14-day infusion, dose-limiting toxicities (DLT) consisting of febrile neutropenia and thrombocytopenia occurred at 4.0 mg/m 2 /day. At 3.0 mg/m 2 /day, 3 patients experienced neutropenia in cycle 2. The dose of 2.0 mg/m 2 /day was well tolerated in 6 patients. In 7-day infusion, grade 4 neutropenia was DLT at 4.0 mg/m 2 /day. The maximum tolerated dose was 3 mg/m 2 /day. Other toxicities included nausea, vomiting, diarrhea, neutropenia, and alopecia. Eight patients had stable disease for >12 weeks. Paired comet assays performed for 7 patients showed an increase in DNA strand breaks at day 8. Pharmacokinetic data showed dose-proportionality for steady-state concentration and AUC of DFP-10917 and its primary metabolite. Conclusion Continuous infusion of DFP-10917 is feasible and well tolerated with myelosuppression as main DLT. The recommended doses are 2.0 mg/m 2 /day and 3.0 mg/m 2 /day on the 14-day and 7-day continuous infusion schedules, respectively. Preliminary activity was suggested. Pharmacodynamic data demonstrate biological activity at the tested doses.

[Injection Pressure Evaluation of the New Venous Catheter with Side Holes for Contrast-enhanced CT/MRI].

PubMed

Fukuda, Junya; Arai, Keisuke; Miyazawa, Hitomi; Kobayashi, Kyouko; Nakamura, Junpei; Suto, Takayuki; Tsushima, Yoshito

2018-01-01

The simulation study was conducted for the new venous catheter with side holes of contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) to evaluate the infusion pressure on four contrast media and several injection speeds. All infusion pressure of the new venous catheter with side holes were less than 15 kg/cm 2 as limitation of extension tube and also reduced the infusion pressure by 15% at the maximum compared to the catheter with single hole. The results suggest that the new venous catheter with side holes can reduce the infusion pressure by power injection of contrast-enhanced CT and MRI.

Description and Preliminary Evaluation of a Diabetes Technology Simulation Course

PubMed Central

Wilson, Rebecca D.; Bailey, Marilyn; Boyle, Mary E.; Seifert, Karen M.; Cortez, Karla Y.; Baker, Leslie J.; Hovan, Michael J.; Stepanek, Jan; Cook, Curtiss B.

2013-01-01

Background We aim to provide data on a diabetes technology simulation course (DTSC) that instructs internal medicine residents in the use of continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring system (CGMS) devices. Methods The DTSC was implemented during calendar year 2012 and conducted in the institution’s simulation center. It consisted of a set of prerequisites, a practicum, and completion of a web-based inpatient CSII-ordering simulation. DTSC participants included only those residents in the outpatient endocrinology rotation. Questionnaires were used to determine whether course objectives were met and to assess the satisfaction of residents with the course. Questionnaires were also administered before and after the endocrine rotation to gauge improvement in familiarity with CSII and CGMS technologies. Results During the first year, 12 of 12 residents in the outpatient endocrinology rotation completed the DTSC. Residents reported that the course objectives were fully met. The mean satisfaction score with the course ranged from 4.0 to 4.9 (maximum, 5), with most variables rated above 4.5. Self-reported familiarity with the operation of CSII and CGMS devices increased significantly in the postrotation survey compared with that on the prerotation survey (both p < .01). Conclusions In this pilot program, simulation-based education increased the perceived familiarity of residents with CSII and CGMS technologies. In light of these preliminary findings, the course will continue to be offered, with further data accrual. Future work will involve piloting the DTSC approach among other types of providers, such as residents in other specialties or inpatient nursing staff. PMID:24351182

Neoadjuvant chemotherapy with continuous infusion of cisplatin and 5-fluorouracil, with or without leucovorin, for locally advanced nasopharyngeal carcinoma.

PubMed

Fonseca, E; Cruz, J J; Rodríguez, C A; Gómez-Bernal, A; Martín, G; Sánchez, P; Nieto, A; Soria, P; Vega, M J; Muñoz, A; Pardal, J L

1996-01-01

Cisplatin-based induction chemotherapy has been extensively tested in nasopharyngeal carcinoma for the improvement of local and systemic control and survival of this disease. In this study, we report the results of the treatment with induction chemotherapy in 40 patients with locally advanced carcinoma of the nasopharynx (LANPC) with four courses of cisplatin (P) 25 mg/m2 per day and 5-fluorouracil (F) 1000 mg/m2 per day both in a 4-days continuous infusion, with or without leucovorin (L) 250 mg/m2 per day in 2-hour infusion at the beginning of daily administration of PF, followed by sequential radiotherapy. All except one were in stage IV. The overall response after induction chemotherapy was 93%, with 55% CR and 38% PR. Definitive overall response after radiotherapy was 98%, with 80% CR and 18% PR. At a maximum follow up of 11 years, the overall survival rate is 55%. Induction chemotherapy with continuous infusion of PF with or without leucovorin followed by radiotherapy is a highly active regimen for the treatment of locally advanced nasopharyngeal carcinoma with response and survival rates comparable to other combinations of sequential or simultaneous chemotherapy and radiotherapy.

High dose infusion of activated protein C (rhAPC) fails to improve neuronal damage and cognitive deficit after global cerebral ischemia in rats.

PubMed

Brückner, Melanie; Lasarzik, Irina; Jahn-Eimermacher, Antje; Peetz, Dirk; Werner, Christian; Engelhard, Kristin; Thal, Serge C

2013-09-13

Recent studies demonstrated anticoagulatory, antiinflammatory, antiapoptotic, and neuroprotective properties of activated protein C (APC) in rodent models of acute neurodegenerative diseases, suggesting APC as promising broad acting therapeutic agent. Unfortunately, continuous infusion of recombinant human APC (rhAPC) failed to improve brain damage following cardiac arrest in rats. The present study was designed to investigate the neuroprotective effect after global cerebral ischemia (GI) with an optimized infusion protocol. Rats were subjected to bilateral clip occlusion of the common carotid arteries (BCAO) and controlled hemorrhagic hypotension to 40 mm Hg for 14 min and a subsequent 5h-infusion of rhAPC (2mg/kg bolus+6 mg/kg/h continuous IV) or vehicle (0.9% NaCl). The dosage was calculated to maintain plasma hAPC activity at 150%. Cerebral inflammation, apoptosis and neuronal survival was determined at day 10. rhAPC infusion did not influence cortical cerebral perfusion during reperfusion and failed to reduce neuronal cell loss, microglia activation, and caspase 3 activity. Even an optimized rhAPC infusion protocol designed to maintain a high level of APC plasma activity failed to improve the sequels following GI. Despite positive reports about protective effects of APC following, e.g., ischemic stroke, the present study supports the notion that infusion of APC during the early reperfusion phase does not result in sustained neuroprotection and fails to improve outcome after global cerebral ischemia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Development of a simulated smart pump interface.

PubMed

Elias, Beth L; Moss, Jacqueline A; Shih, Alan; Dillavou, Marcus

2014-01-01

Medical device user interfaces are increasingly complex, resulting in a need for evaluation in clinicallyaccurate settings. Simulation of these interfaces can allow for evaluation, training, and use for research without the risk of harming patients and with a significant cost reduction over using the actual medical devices. This pilot project was phase 1 of a study to define and evaluate a methodology for development of simulated medical device interface technology to be used for education, device development, and research. Digital video and audio recordings of interface interactions were analyzed to develop a model of a smart intravenous medication infusion pump user interface. This model was used to program a high-fidelity simulated smart intravenous medication infusion pump user interface on an inexpensive netbook platform.

Development of cutaneous gangrene during continuous peripheral infusion of vasopressin.

PubMed Central

Anderson, J R; Johnston, G W

1983-01-01

Five patients given vasopressin by infusion to reduce portal hypertension developed signs of cutaneous gangrene 18-24 hours after the start of the infusion. Four patients were treated by application of local dressings; in three cases the lesions healed, but the fourth patient died from variceal haemorrhage. The remaining patient required split skin grafting but died 48 hours after operation. The mechanism of this effect of vasopressin is not clear, but if local blanching of the skin is noted during infusion the catheter should be flushed immediately with a vasodilator in an effort to counteract the drug's vasoconstrictor effect. PMID:6416538

Event and Cost Offsets of Switching 20% of the Type 1 Diabetes Population in Germany From Multiple Daily Injections to Continuous Subcutaneous Insulin Infusion: A 4-Year Simulation Model.

PubMed

Zöllner, York Francis; Ziegler, Ralph; Stüve, Magnus; Krumreich, Julia; Schauf, Marion

2016-09-01

Most patients with type 1 diabetes (T1D) administer insulin by multiple daily injections (MDI). However, continuous subcutaneous insulin infusion (CSII) therapy has been shown to improve glycemic control compared with MDI. The objective was to determine the key medical event and cost offsets generated over a 4-year period by introducing CSII to T1D patients who have inadequately controlled glucose metabolism on MDI in Germany. A decision-analytic budget impact model, simulating a treatment switch scenario, was developed. In the base case, all T1D patients received MDI, while in the switch scenario, 20% of the eligible T1D population, randomly selected, moved to CSII. The model focused on 2 medical endpoints and their corresponding cost offsets: severe hypoglycemic events requiring hospitalization (SHEH) and complication-borne diabetic events (CDEs) avoided. Event rates and costs were taken from the literature and official sources, adopting a health insurance perspective. Compared with the base case, treating 20% of patients with CSII in the switch scenario resulted in 47 864 fewer SHEH and 5543 fewer CDEs. This led to total cost offsets of €183 085 281 within the 4-year time horizon. Of these, 92% were driven by avoided SHEH. Compared to an expected budget impact (cost increase) of 83%, only treatment costs considered, the total impact of the switch scenario amounted merely to a 24.5% increase in costs (reduction by 58.5% points; a factor of 3.4). The use of CSII resulted in fewer SHEH and CDEs compared to MDI. The incurred CSII implementation costs are hence offset to a substantial degree by cost savings in complication treatment. © 2016 Diabetes Technology Society.

Necessity of heparin for maintaining peripheral venous catheters: A systematic review and meta-analysis

PubMed Central

You, Tao; Jiang, Jianliang; Chen, Jianchang; Xu, Weiting; Xiang, Li; Jiao, Yang

2017-01-01

Heparin has typically been used as a flushing or infusion solution for vascular lines in daily practice. However, several clinical trials have yielded controversial results about the benefits of heparin in maintaining peripheral venous catheters. The present meta-analysis was conducted to evaluate the efficacy of heparin on the patency profiles and complications in peripheral intravenous catheters. PubMed, Embase and Cochrane Central Register of Controlled Trials were searched up to February 2016 for randomized controlled trials comparing heparin with placebo in maintaining peripheral intravenous catheters. Additional studies were retrieved from the reference lists of identified articles. In total 32 eligible studies were included, from which the pooled standard mean difference (SMD), relative risk (RR) and corresponding 95% confidence interval (CI) were calculated. The use of heparin as a continuous infusion significantly prolonged the duration of patency (SMD, 0.90; 95% CI, 0.48–1.32; P<0.001), reduced rates of infusion failure (RR, 0.83; 95% CI, 0.76–0.92; P<0.001) and occlusion (RR, 0.82; 95% CI, 0.69–0.98; P<0.05) in a peripheral intravenous catheter. However, there were no significant changes in the duration of patency and infusion failure when heparin was used intermittently as a flushing solution, although a significantly decreased risk of occlusion was observed in this setting (RR, 0.80; 95% CI, 0.66–0.98; P<0.05). Furthermore, the risk of phlebitis was significantly decreased by both continuous infusion (RR, 0.66; 95% CI, 0.58–0.75; P<0.01) and intermittent flushing (RR, 0.70; 95% CI, 0.56–0.86; P<0.01) of heparin in peripheral venous catheters. In conclusion, the use of heparin as continuous infusion in peripheral intravenous catheters improved the duration of patency, reduced infusion failure and phlebitis, whereas heparin as intermittent flushing showed more benefits in ameliorating phlebitis rather than in patency profiles. PMID:28810636

Protocol for a randomised crossover trial to evaluate patient and nurse satisfaction with electronic and elastomeric portable infusion pumps for the continuous administration of antibiotic therapy in the home: the Comparing Home Infusion Devices (CHID) study

PubMed Central

Ryan, Melissa K; Ritchie, Brett; Sluggett, Janet K; Sluggett, Andrew J; Ralton, Lucy; Reynolds, Karen J

2017-01-01

Introduction Previous studies comparing satisfaction with electronic and elastomeric infusion pumps are limited, and improvements in size and usability of electronic pumps have since occurred. The Comparing Home Infusion Devices (CHID) study plans to assess patient and nurse satisfaction with an elastomeric and electronic pump for delivering intravenous antibiotic treatment in the home. Secondary objectives are to determine pump-related complications and actual antibiotic dose administered, evaluate temperature variation and compare pump operating costs. Methods and analysis The CHID study will be a randomised, crossover trial. A trained research nurse will recruit patients with infectious disease aged ≥18 years and prescribed ≥8 days of continuous intravenous antibiotic therapy from the Royal Adelaide Hospital (RAH) (Adelaide, Australia). Patients will be randomised to receive treatment at home via an elastomeric (Baxter Infusor) or an electronic (ambIT Continuous) infusion pump for 4–7 days, followed by the other for a further 4–7 days. Patient satisfaction will be assessed by a 10-item survey to be completed at the end of each arm. Nurse satisfaction will be assessed by a single 24-item survey. Patient logbooks and case notes from clinic visits will be screened to identify complications. Pumps/infusion bags will be weighed to estimate the volume of solution delivered. Temperature sensors will record skin and ambient temperatures during storage and use of the pumps throughout the infusion period. Costs relating to pumps, consumables, antibiotics and servicing will be determined. Descriptive statistics will summarise study data. Ethics and dissemination This study has been approved by the RAH Human Research Ethics Committee (HREC/16/RAH/133 R20160420, version 6.0, 5 September 2016). Study results will be disseminated through peer-reviewed publications and conference presentations. The CHID study will provide key insights into patient and provider satisfaction with elastomeric and electronic infusion pumps and inform future device selection. Trial registration number ACTRN12617000251325; Pre-results. PMID:28760798

Protocol for a randomised crossover trial to evaluate patient and nurse satisfaction with electronic and elastomeric portable infusion pumps for the continuous administration of antibiotic therapy in the home: the Comparing Home Infusion Devices (CHID) study.

PubMed

Hobbs, Jodie G; Ryan, Melissa K; Ritchie, Brett; Sluggett, Janet K; Sluggett, Andrew J; Ralton, Lucy; Reynolds, Karen J

2017-07-31

Previous studies comparing satisfaction with electronic and elastomeric infusion pumps are limited, and improvements in size and usability of electronic pumps have since occurred. The Comparing Home Infusion Devices (CHID) study plans to assess patient and nurse satisfaction with an elastomeric and electronic pump for delivering intravenous antibiotic treatment in the home. Secondary objectives are to determine pump-related complications and actual antibiotic dose administered, evaluate temperature variation and compare pump operating costs. The CHID study will be a randomised, crossover trial. A trained research nurse will recruit patients with infectious disease aged ≥18 years and prescribed ≥8 days of continuous intravenous antibiotic therapy from the Royal Adelaide Hospital (RAH) (Adelaide, Australia). Patients will be randomised to receive treatment at home via an elastomeric (Baxter Infusor) or an electronic (ambIT Continuous) infusion pump for 4-7 days, followed by the other for a further 4-7 days. Patient satisfaction will be assessed by a 10-item survey to be completed at the end of each arm. Nurse satisfaction will be assessed by a single 24-item survey. Patient logbooks and case notes from clinic visits will be screened to identify complications. Pumps/infusion bags will be weighed to estimate the volume of solution delivered. Temperature sensors will record skin and ambient temperatures during storage and use of the pumps throughout the infusion period. Costs relating to pumps, consumables, antibiotics and servicing will be determined. Descriptive statistics will summarise study data. This study has been approved by the RAH Human Research Ethics Committee (HREC/16/RAH/133 R20160420, version 6.0, 5 September 2016). Study results will be disseminated through peer-reviewed publications and conference presentations. The CHID study will provide key insights into patient and provider satisfaction with elastomeric and electronic infusion pumps and inform future device selection. ACTRN12617000251325; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Continuous Intravenous Milrinone Therapy in Pediatric Outpatients.

PubMed

Curley, Michelle; Liebers, Jill; Maynard, Roy

Milrinone is a phosphodiesterase 3 inhibitor with both positive inotropic and vasodilator properties. Administered as a continuous infusion, milrinone is indicated for the short-term treatment of patients with acute decompensated heart failure. Despite limited data supporting long-term milrinone therapy in adults with congestive heart failure, children managed as outpatients may benefit from continuous milrinone as a treatment for cardiac dysfunction, as a destination therapy for cardiac transplant, or as palliative therapy for cardiomyopathy. The aim of this article is to review the medical literature and describe a home infusion company's experience with pediatric outpatient milrinone therapy.

Continuous Intravenous Milrinone Therapy in Pediatric Outpatients

PubMed Central

Curley, Michelle; Liebers, Jill

2017-01-01

Milrinone is a phosphodiesterase 3 inhibitor with both positive inotropic and vasodilator properties. Administered as a continuous infusion, milrinone is indicated for the short-term treatment of patients with acute decompensated heart failure. Despite limited data supporting long-term milrinone therapy in adults with congestive heart failure, children managed as outpatients may benefit from continuous milrinone as a treatment for cardiac dysfunction, as a destination therapy for cardiac transplant, or as palliative therapy for cardiomyopathy. The aim of this article is to review the medical literature and describe a home infusion company's experience with pediatric outpatient milrinone therapy. PMID:28248808

Metabolic modeling of dynamic brain 13C NMR multiplet data: Concepts and simulations with a two-compartment neuronal-glial model

PubMed Central

Shestov, Alexander A.; Valette, Julien; Deelchand, Dinesh K.; Uğurbil, Kâmil; Henry, Pierre-Gilles

2016-01-01

Metabolic modeling of dynamic 13C labeling curves during infusion of 13C-labeled substrates allows quantitative measurements of metabolic rates in vivo. However metabolic modeling studies performed in the brain to date have only modeled time courses of total isotopic enrichment at individual carbon positions (positional enrichments), not taking advantage of the additional dynamic 13C isotopomer information available from fine-structure multiplets in 13C spectra. Here we introduce a new 13C metabolic modeling approach using the concept of bonded cumulative isotopomers, or bonded cumomers. The direct relationship between bonded cumomers and 13C multiplets enables fitting of the dynamic multiplet data. The potential of this new approach is demonstrated using Monte-Carlo simulations with a brain two-compartment neuronal-glial model. The precision of positional and cumomer approaches are compared for two different metabolic models (with and without glutamine dilution) and for different infusion protocols ([1,6-13C2]glucose, [1,2-13C2]acetate, and double infusion [1,6-13C2]glucose + [1,2-13C2]acetate). In all cases, the bonded cumomer approach gives better precision than the positional approach. In addition, of the three different infusion protocols considered here, the double infusion protocol combined with dynamic bonded cumomer modeling appears the most robust for precise determination of all fluxes in the model. The concepts and simulations introduced in the present study set the foundation for taking full advantage of the available dynamic 13C multiplet data in metabolic modeling. PMID:22528840

Population pharmacokinetics and dosing simulations of imipenem in serious bacteraemia in immunocompromised patients with febrile neutropenia.

PubMed

Jaruratanasirikul, Sutep; Wongpoowarak, Wibul; Jullangkoon, Monchana; Samaeng, Maseetoh

2015-02-01

The aims of this study were to i) reveal the population pharmacokinetics; and ii) assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) (defined as the expected population PTA for a specific drug dose and a specific population of microorganisms) of imipenem in febrile neutropenic patients with bacteraemia. Ten patients were randomised into two groups: Group I received a 0.5-h infusion of 0.5 g of imipenem every 6 h (q6h) for 8 doses; and Group II received a 4-h infusion of 0.5 g q6h for 8 doses. A Monte Carlo simulation was performed to determine the PTA. The volume of distribution and total clearance of imipenem were 20.78 ± 1.35 l and 23.19 ± 1.34 l/h, respectively. Only a 4-h infusion of 1 g q6h regimen achieved a PTA >93% for 80% T>MIC for a MIC of 2 μg/ml. A 4-h infusion of all simulated regimens and a 0.5-h infusion of 0.5 g q6h and 1 g q6h achieved targets (CFR ≥ 90%) against Escherichia coli and Klebsiella spp. However, against Pseudomonas aeruginosa and Acinetobacter spp., no regimens achieved their targets. In conclusion, the results indicate that a higher than manufacturer's dosage recommendation is required to maximize the activity of imipenem. Copyright © 2014 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

Periosteal infusion of bupivacaine/morphine post sternal fracture: a new analgesic technique.

PubMed

Duncan, Michael A; McNicholas, Walter; O'Keeffe, Declan; O'Reilly, Maeve

2002-01-01

Sternal fracture pain is severe and is difficult to alleviate due to the forces acting on the chest wall during respiration. We describe a continuous infusion regional analgesic technique for pain due to sternal fracture. A 47-year-old woman presented with a spontaneous sternal fracture, precluding effective coughing. Diclofenac and increasing doses of opioids did not give adequate pain relief and led to opioid toxicity. Two brief periods of analgesia were achieved with deep subcutaneous infiltration of bupivacaine. An epidural catheter was positioned periosteally, and an infusion of bupivacaine was commenced at 5 mL/h, achieving long-lasting analgesia. The bupivacaine concentration was reduced in a stepwise fashion from 0.5% to 0.25% and was changed to levobupivacaine after 3 days. Adding morphine (5 mg/60 mL levobupivicaine) permitted a reduction in infusion rate. The catheter was removed after 14 days because a local infection developed that resolved uneventfully with antibiotic therapy. Continuous infusion of local anesthetic and opioid to a sternal fracture site using a periosteally positioned catheter led to successful analgesia and hence improved respiratory function. Clinicians should consider placing a periosteal catheter when pain associated with sternal fracture cannot be adequately controlled with conventional methods.

Successful treatment with granulocyte-colony stimulating factor for ritodrine-induced neutropenia in a twin pregnancy.

PubMed

Wang, Chen-Yu; Lai, Yu-Ju; Hwang, Kwei-Shuai; Chen, Chi-Huang; Yu, Mu-Hsien; Chen, Huei-Tsung; Su, Her-Young

2016-10-01

Neutropenia developed after continuous intravenous infusion of ritodrine hydrochloride (Yutopar) for preterm uterine contractions in a twin pregnancy. We successfully returned the low neutrophil count to the normal range after discontinuation of infusion of ritodrine and treatment with granulocyte colony stimulating factor (G-CSF). A 34-year-old woman with twin pregnancy was treated with ritodrine for preterm uterine contractions at 27 weeks and 6 days gestation. Neutropenia developed after continuous intravenous infusion of ritodrine for about 4 weeks. We ceased the ritodrine infusion immediately and treated the neutropenia with G-CSF. A cesarean delivery was performed the day after cessation of the ritodrine infusion because of uncontrolled preterm labor. There were no adverse side effects or infectious complications in the mother or the newborns. The maternal neutrophil count recovered to the normal range 4 days after administration of G-CSF. Based on prior case reports and the clinical presentation of our case, G-CSF may be a useful treatment for pregnant women with ritodrine-induced neutropenia. However, more clinical studies are required to confirm the safety and efficacy of this treatment. Copyright © 2016. Published by Elsevier B.V.

Effect of microbubble contrast on intracranial blood flow velocity assessed by transcranial Doppler.

PubMed

Logallo, Nicola; Fromm, Annette; Waje-Andreassen, Ulrike; Thomassen, Lars; Matre, Knut

2014-03-01

Ultrasound contrast agents (UCA) salvage a considerable number of transcranial Doppler (TCD) exams which would have failed because of poor bone window. UCA bolus injection causes an undesirable increase in measured blood flow velocity (BFV). The effect of UCA continuous infusion on measured BFV has not been investigated, and some in vitro experiments suggest that gain reduction during UCA administration may also influence measured BFV. This study aimed to investigate the effect of UCA continuous infusion on BFV measured by TCD and the influence of gain reduction on these measurements in a clinical setting. The right middle cerebral artery of ten patients with optimal bone window was insonated using a 2 MHz probe. UCA were administered using an infusion pump. BFV was measured (1) at baseline, (2) during UCA infusion, (3) during UCA infusion with gain reduction, and (4) after UCA wash-out phase. Gain reduction was based on the agreement between two neurosonographers on the degree of gain reduction necessary to restore baseline Doppler signal intensity (DSI). Actual DSI was estimated offline by analysis of raw data. BFV measured during UCA infusion with no gain adjustment was significantly higher than baseline BFV [peak systolic velocity (PSV): 85.1 ± 19.7 vs. 74.4 ± 19.7 cm/s, p < 0.0001; Mean velocity (MV): 56.5 ± 11.8 vs. 50.2 ± 12.3 cm/s, p < 0.0001]. BFV measured during UCA infusion with gain reduction was not significantly higher than baseline BFV (PSV: 74.3 ± 18.9 vs. 74.4 ± 19.4 cm/s, p = 0.8; MV: 49.4 ± 11.0 vs. 50.2 ± 12.3 cm/s, p = 0.8). Actual DSI during UCA infusion with gain reduction was not significantly higher than baseline DSI (13 ± 1 vs. 13 ± 1 dB). This study shows that UCA continuous infusion leads to an increase in measured BFV which may be counteracted by reducing Doppler gain thus restoring pre-contrast DSI.

Intravenous Sedation with Low-Dose Dexmedetomidine: Its Potential for Use in Dentistry

PubMed Central

Ogawa, Sachie; Seino, Hiroaki; Ito, Hiroshi; Yamazaki, Shinya; Ganzberg, Steven; Kawaai, Hiroyoshi

2008-01-01

This study investigated the physiologic and sedative parameters associated with a low-dose infusion of dexmedetomidine (Dex). Thirteen healthy volunteers were sedated with Dex at a loading dose of 6 mcg/kg/h for 5 minutes and a continuous infusion dose of 0.2 mcg/kg/h for 25 minutes. The recovery process was observed for 60 minutes post infusion. The tidal volume decreased significantly despite nonsignificant changes in respiratory rate, minute ventilation, oxygen saturation, and end-tidal carbon dioxide. The mean arterial pressure and heart rate also decreased significantly but within clinically acceptable levels. Amnesia to pin prick was present in 69% of subjects. A Trieger dot test plot error ratio did not show a significant change at 30 minutes post infusion despite a continued significant decrease in bispectral index. We conclude that sedation with a low dose of Dex appears to be safe and potentially efficacious for young healthy patients undergoing dental procedures. PMID:18788843

Tolerance to the hypothermic but not to the analgesic effect of [D-Trp11]neurotensin during the semichronic intracerebroventricular infusion of the peptide in rats.

PubMed

Dubuc, I; Pain, C; Suaudeau, C; Costentin, J

1994-01-01

The peptidase-resistant derivative of neurotensin, [D-Trp11]neurotensin, has been continuously infused intracerebroventricularly (75 ng/h) with an osmotic minipump for 10 days. On several days during this infusion the locomotor activity, the body temperature, the food intake, the body weight, and the nociceptive response in the plantar test were measured. A nonsignificant decrease of body temperature and a sustained analgesic effect were observed at each time considered. The response to a test dose of [D-Trp11]neurotensin (75 ng per rat) injected intracerebroventricularly at the 10th day of the chronic infusion revealed a complete tolerance to its hypothermic effect. Thus, it appears that the analgesic effect of [D-Trp11]neurotensin is independent of a hypothermic or an incapacitating effect of the peptide and does not give rise to tolerance after a 10-day continuous administration, in contrast to the hypothermic effect.

Intraosseous vascular access in the treatment of chemical warfare casualties assessed by advanced simulation: proposed alteration of treatment protocol.

PubMed

Vardi, Amir; Berkenstadt, Haim; Levin, Inbal; Bentencur, Ariel; Ziv, Amitai

2004-06-01

Current treatment protocols for chemical warfare casualties assume no IV access during the early treatment stages. Time constraints in mass casualty scenarios, impaired manual dexterity of medical personnel wearing protective gear, and victims' complex clinical presentations render standard IV access techniques impractical. A newly developed spring-driven, trigger-operated intraosseous infusion device may offer an effective solution. Sophisticated simulators were developed and used to mimic scenarios of chemical warfare casualties for assessing the feasibility of intraosseous infusion delivery. We evaluated the clinical performance of medical teams in full protective gear. The success rate in intraosseous insertion, time to completion of treatment goals, and outcome were measured in a simulated setting. Medical teams from major hospitals in Israel, designated for emergency response in a real chemical warfare mass casualty scenario, were trained in a simulated setting. All 94 participating physicians were supplied with conventional treatment modalities: only the 64 study group physicians received intraosseous devices. The simulated survival rate was 73.4% for the study group and 3.3% for the controls (P < 0.001). Treatment goals were achieved within 3.5 min (range, 1-9 min) in the study group and within >10 min for controls (P < 0.001), and the complication rate for intraosseous use was 13.8%. Personnel satisfaction with the intraosseous device was unanimous and high. New-generation intraosseous infusions have great potential value in the early treatment stages of chemical warfare casualties. In a chemical warfare mass casualty scenario, the protective gear worn by medical personnel, the time constraints, and the casualties' medical condition impose limitations on the establishment of IV access during early treatment of the victims. A spring-driven, trigger-operated intraosseous infusion delivery system may offer an effective solution.

[Autocontrol of muscle relaxation with vecuronium].

PubMed

Sibilla, C; Zatelli, R; Marchi, M; Zago, M

1990-01-01

The optimal conditions for maintaining desired levels of muscle relaxation with vecuronium are obtained by means of the continuous infusion (I.V.) technique. A frequent correction of the infusion flow is required, since it is impossible to predict the exact amount for the muscle relaxant in single case. In order to overcome such limits the authors propose a very feasible infusion system for the self-control of muscle relaxation; furthermore they positively consider its possible daily clinical application.

Physical and chemical stability of high-dose ifosfamide and mesna for prolonged 14-day continuous infusion.

PubMed

Zhang, YanPing; Kawedia, Jitesh D; Myers, Alan L; McIntyre, Chelsey M; Anderson, Peter M; Kramer, Mark A; Culotta, Kirk S

2014-02-01

Ifosfamide plus mesna have been used recently in a high-dose regimen that allows this chemotherapy to be given to outpatients with less toxicity over 14 days using a portable pump. However, there is a need for published stability information. The aim of this study was to investigate the physicochemical stability of ifosfamide with mesna in normal saline at room temperature over a prolonged period of 14 days. Infusion solutions of 1:1 ifosfamide and mesna at final concentrations of 10, 20 and 30 mg/mL were prepared with 0.9% sodium chloride in PVC bags. Solutions were stored at room temperature. Concentrations of ifosfamide and mesna were measured at 0 and 1, 3, 7 and 14 days using a stability-indicating reversed phase high-performance liquid chromatography (HPLC) assay with ultraviolet detection. Ifosfamide and mesna were both physicochemically stable (>94%) for 14 days in all tested infusion solutions (10, 20 and 30 mg/mL). Our stability data indicate that ifosfamide and mesna (1:1) combination can be administered as a prolonged continuous infusion with portable pump in an outpatient setting without replacement of the infusion bag. We suggest 20 mg/mL as a reasonable concentration for infusion rates of about 2-4 cc/hr over prolonged periods of time.

Physical and Chemical Stability of Urapidil in 0.9% Sodium Chloride in Elastomeric Infusion Pump.

PubMed

Tomasello, Cristina; Leggieri, Anna; Rabbia, Franco; Veglio, Franco; Baietto, Lorena; Fulcheri, Chiara; De Nicolò, Amedeo; De Perri, Giovanni; D'Avolio, Antonio

2016-01-01

Urapidil is an antihypertensive agent, usually administered through intravenous bolus injection, slow-intravenous infusion, or continuous-drug infusion by perfusor. Since to date no evidences are available on drug stability in elastomeric pumps, patients have to be hospitalized. The purpose of this study was to validate an ultra-performance liquid chromatographic method to evaluate urapidil stability in an elastomeric infusion pump, in order to allow continuous infusion as home-care treatment. Analyses were conducted by diluting urapidil in an elastomeric pump. Two concentrations were evaluated: 1.6 mg/mL and 3.3 mg/mL. For the analyses, a reverse-phase ultra-performance liquid chromatographic- photodiode array detection instrument was used. Stressed degradation, pH changes, and visual clarity were used as stability indicators up to 10 days after urapidil solution preparation. The drug showed no more than 5% degradation during the test period at room temperature. No pH changes and no evidences of incompatibility were observed. Stress tests resulted in appreciable observation of degradation products. Considering the observed mean values, urapidil hydrochloride in sodium chloride 0.9% in elastomeric infusion pumps is stable for at least 10 days. These results indicate that this treatment could be administered at home for a prolonged duration (at least 7 days) with a satisfactory response. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Propionate supplementation improves nitrogen use by reducing urea flux in sheep.

PubMed

Agarwal, U; Hu, Q; Bequette, B J

2015-10-01

Feeding and postruminal infusion of propionate is known to increase N retention in ruminants. Our aim was to determine the role of rumen propionate on urea N recycling and gluconeogenesis in growing sheep. In Exp. 1, wether sheep ( = 6; 32.5 ± 3.57 kg BW) fitted with a rumen cannula were fed to 1.8 × ME requirement a concentrate-type ration (172 g CP/kg DM and 10.4 MJ ME/kg DM) and continuously infused into the rumen with isoenergetic (10% of dietary ME intake) solutions of either sodium acetate (control) or sodium propionate for 9-d periods in a crossover design. In Exp. 2, a different group of wether sheep ( = 5; 33.6 ± 3.70 kg BW) fitted with a rumen cannula were fed, on an isonitrogenous basis, either a control (151 g CP/kg DM and 8.4 MJ ME/kg DM) or sodium propionate-supplemented (139 g CP/kg DM and 8.9 MJ ME/kg DM) diet at 2-h intervals. [N] urea was continuously infused intravenously for the last 5 d of each period, and total urine was collected by vacuum and feces were collected by a harness bag. Over the last 12 h, [C]glucose was continuously infused intravenously and hourly blood samples were collected during the last 5 h. Propionate treatments increased ( < 0.001) the proportion of rumen propionate in both experiments. In Exp. 1, N retention was not affected by propionate infusion as compared with isoenergetic acetate. There was no effect on urea entry (synthesis) rate (UER) in Exp. 1; however, sodium propionate infusion tended ( < 0.1) to increase urinary urea elimination (UUE). In Exp. 2, feeding propionate increased ( < 0.01) N retention by 0.8 g N/d. In addition, UER was reduced by approximately 2 g urea N/d, leading to a reduction ( < 0.05) in UUE (7.0 vs. 6.2 g urea N/d). Between the 2 experiments, the proportion of UER recycled to the gut was greater with the forage-type diet in Exp. 2 (approximately 60%) compared with the concentrate-type diet in Exp. 1 (approximately 40%), although urea N fluxes across the gut remained unchanged in both experiments. In Exp. 1, glucose entry and gluconeogenesis were greater ( < 0.05) and plasma glucose tended ( < 0.1) to be greater with sodium propionate infusion than with sodium acetate infusion, but there was no difference in Cori cycling. In Exp. 2, glucose entry, gluconeogenesis, Cori cycling, and plasma glucose increased ( < 0.05) with dietary propionate. Our studies indicate that propionate inclusion in feed, but not continuous infusion in to the rumen, improves N utilization in growing sheep. The propionate effect is likely mediated by providing additional precursors for gluconeogenesis.

Assessment of implantable infusion pumps for continuous infusion of human insulin in rats: potential for group housing.

PubMed

Jensen, Vivi Flou Hjorth; Mølck, Anne-Marie; Mårtensson, Martin; Strid, Mette Aagaard; Chapman, Melissa; Lykkesfeldt, Jens; Bøgh, Ingrid Brück

2017-06-01

Group housing is considered to be important for rats, which are highly sociable animals. Single housing may impact behaviour and levels of circulating stress hormones. Rats are typically used in the toxicological evaluation of insulin analogues. Human insulin (HI) is frequently used as a reference compound in these studies, and a comparator model of persistent exposure by HI infusion from external pumps has recently been developed to support toxicological evaluation of long-acting insulin analogues. However, this model requires single housing of the animals. Developing an insulin-infusion model which allows group housing would therefore greatly improve animal welfare. The aim of the present study was to investigate the suitability of implantable infusion pumps for HI infusion in group-housed rats. Group housing of rats implanted with a battery-driven pump proved to be possible. Intravenous infusion of HI lowered blood glucose levels persistently for two weeks, providing a comparator model for use in two-week repeated-dose toxicity studies with new long-acting insulin analogues, which allows group housing, and thereby increasing animal welfare compared with an external infusion model.

Mechanism of delayed intracranial hypertension after cerebroventricular infusions in conscious rats

NASA Technical Reports Server (NTRS)

Morrow, B. A.; Holt, M. R.; Starcevic, V. P.; Keil, L. C.; Severs, W. B.

1992-01-01

Prior studies showed that cerebroventricular infusions of artificial cerebrospinal fluid, 8 microliter/min for 10 min, followed by a 10 min rest and a 24 h infusion of 0.5 microliters/min, raised cerebrospinal fluid pressure (CSFp) of conscious, unrestrained rats after about 2 h. Here, we report that the 10 min infusion alone evoked a delayed, prolonged rise in CSFp. Pressure during the infusion itself rose and recovered quickly, as is usually reported. Pressure/volume tests, used to calculate resistance to outflow (Ro) and compliance (C), revealed that infusions increased Ro and decreased C, after a delay (P less than 0.05). The rise in CSFp after infusion was blocked by pretreatment with acetazolamide + ouabain (P less than 0.05), but the delayed changes in Ro and C were unaffected. We suggest that the 10 min infusion of a sterile, balanced salt solution has a primary effect that increases Ro; as CSF synthesis continues, C is exhausted and the delayed rise in CSFp ensues. This non-traumatic method of raising CSFp may be a useful method to study intracranial fluid dynamics.

Intravenous medication safety and smart infusion systems: lessons learned and future opportunities.

PubMed

Keohane, Carol A; Hayes, Judy; Saniuk, Catherine; Rothschild, Jeffrey M; Bates, David W

2005-01-01

The Institute of Medicine report To Err Is Human: Building a Safe Health System greatly increased national awareness of the need to improve patient safety in general and medication safety in particular. Infusion-related errors are associated with the greatest risk of harm, and "smart" (computerized) infusion systems are currently available that can avert high-risk errors and provide previously unavailable data for continuous quality improvement (CQI) efforts. As healthcare organizations consider how to invest scarce dollars, infusion nurses have a key role to play in assessing need, evaluating technology, and selecting and implementing specific products. This article reviews the need to improve intravenous medication safety. It describes smart infusion systems and the results they have achieved. Finally, it details the lessons learned and the opportunities identified through the use of smart infusion technology at Brigham and Women's Hospital in Boston, Massachusetts.

[Dose-intensive chemotherapy with continuous infusion 5-fluorouracil].

PubMed

Tichler, T; Ghodsizade, E; Katz, A; Rath, P; Berger, R; Brenner, H

1999-11-01

54 patients with advanced malignancy refractory to chemotherapy were studied to evaluate efficacy and toxicity of continuous infusion of 5-fluorouracil (5FU) given for 3 weeks. We report results of the first 156 courses given in combination with other drugs. 19 (37%) of the 54 responded, including 3 (6%) with complete response. Toxicity was acceptable, with mucositis in 13 (26%) and 3 (6%) with grade II-III toxicity. Results and toxicity profile were compatible with further disease-oriented studies using this dose-intensive program.

Comparative analysis of Micrococcus luteus isolates from blood cultures of patients with pulmonary hypertension receiving epoprostenol continuous infusion.

PubMed

Hirata, Yoshinori; Sata, Makoto; Makiuchi, Yuko; Morikane, Keita; Wada, Akihito; Okabe, Nobuhiko; Tomoike, Hitonobu

2009-12-01

During the period 2002-2008, at the National Cardiovascular Center, Osaka, 28 Micrococcus luteus isolates and one Kocuria spp. isolate were obtained from blood cultures of pulmonary hypertension (PH) patients who were receiving continuous infusion therapy with epoprostenol. Pulsed-field gel electrophoresis patterns of the isolates were unrelated, suggesting that the infections had multiple origins. The preparation of epoprostenol solution by patients themselves was thought to be a risk factor.

Safety Risks Among Home Infusion Nurses and Other Home Health Care Providers

PubMed Central

Galligan, Catherine; Quinn, Margaret

2017-01-01

In the United States, home health care (HHC) is a rapidly growing industry and home infusion therapy is a rapidly growing market. HHC can present substantial occupational safety and health (OSH) risks. This article summarizes major OSH risks relevant to home infusion therapy by illustrating them through real-life scenarios collected systematically using qualitative research methods by the National Institute for Occupational Safety and Health-funded research projects at the University of Massachusetts Lowell. The need for home infusion therapy will continue to grow in the future, and safety interventions to prevent or minimize OSH risks are essential. PMID:28683000

Severe skull base osteomyelitis caused by Pseudomonas aeruginosa with successful outcome after prolonged outpatient therapy with continuous infusion of ceftazidime and oral ciprofloxacin: a case report.

PubMed

Conde-Díaz, Cristina; Llenas-García, Jara; Parra Grande, Mónica; Terol Esclapez, Gertrudis; Masiá, Mar; Gutiérrez, Félix

2017-02-21

Skull base osteomyelitis is an uncommon disease that usually complicates a malignant external otitis with temporal bone involvement. It affects predominantly diabetic and immunocompromised males and has a high mortality rate. Pseudomonas aeruginosa is the most common causative organism. Currently, there is no consensus about the best therapeutic option. Here we describe a case of severe skull base osteomyelitis caused by Pseudomonas aeruginosa with progressive palsy of cranial nerves that was successfully managed with prolonged outpatient continuous infusion of ceftazidime plus oral ciprofloxacin. A 69-year-old Caucasian man presented with dysphagia, headache, and weight loss. He complained of left earache and purulent otorrhea. Over the following weeks he developed progressive palsy of IX, X, VI, and XII cranial nerves and papilledema. A petrous bone computed tomography scan showed a mass in the left jugular foramen with a strong lytic component that expanded to the cavum. A biopsy was then performed and microbiological cultures grew Pseudomonas aeruginosa. After 6 weeks of parenteral antibiotic treatment, our patient was discharged and treatment was continued with a domiciliary continuous infusion of a beta-lactam through a peripherally inserted central catheter, along with an oral fluoroquinolone for 10 months. Both radiological and clinical responses were excellent. Skull base osteomyelitis is a life-threating condition; clinical suspicion and correct microbiological identification are key to achieve an accurate and timely diagnosis. Due to the poor outcome of Pseudomonas aeruginosa skull base osteomyelitis, prolonged outpatient parenteral antibiotic therapy administered by continuous infusion could be a valuable option for these patients.

[Clinical evaluation and problem of intra-arterial infusion chemotherapy of liver metastasis from digestive organ cancer].

PubMed

Ohya, T; Fukunaga, J; Kitahama, H; Okuyama, A; Seki, T; Tsurui, K; Saka, M; Sasagawa, M; Hishinuma, S; Kotake, K

1990-08-01

Intra-arterial infusion chemotherapy using an implantable reservoir was used for 22 patients with liver metastasis from September 1986 to March 1990. The material consisted of 8 subjects with gastric cancer and 14 with colorectal cancer. One had metastasis in one lobe (H1), 10 had a few scattered metastases in both lobes (H2) and 11 had numerous metastases in both lobes (H3). In 5 cases, a reservoir was implanted to prevent the recurrence after hepatectomy. Infusion catheter was placed in the proper hepatic artery in 5 cases via the gastroduodenal artery at laparotomy and it was carried out subcutaneously via the femoral artery in 17 cases. In all cases intra-arterial infusion of 5-FU was continuously administered followed by intermittent one shot injection of ADM. The clinical effectiveness of the therapy was well evaluated. One-year cumulative survival rate of all cases by Kaplan-Meier method was 55% and that of H2 cases was 78%. No recurrence was noted in post hepatectomy cases. Eight cases (36.3%) showed remarkable complications, which made it impossible to continue intra-arterial infusion chemotherapy: hepatic artery occlusion (3 cases), infection (2 cases), abdominal pain (1 case), hematoma in the implanted site (1 case) and dislocation of the infusion catheter (1 case). From the present study, it is considered that intra-arterial infusion chemotherapy is a useful procedure for the control of liver metastasis. Regimens for improved chemotherapy and the maintenance of more useful and safer catheters should therefore be investigated for further development of the therapeutical estimation.

Improved vascularization of planar membrane diffusion devices following continuous infusion of vascular endothelial growth factor.

PubMed

Trivedi, N; Steil, G M; Colton, C K; Bonner-Weir, S; Weir, G C

2000-01-01

Improving blood vessel formation around an immunobarrier device should improve the survival of the encapsulated tissue. In the present study we investigated the formation of new blood vessels around a planar membrane diffusion device (the Baxter Theracyte System) undergoing a continuous infusion of vascular endothelial growth factor through the membranes and into the surrounding tissue. Each device (20 microl) had both an inner immunoisolation membrane and an outer vascularizing membrane. Human recombinant vascular endothelial growth factor-165 was infused at 100 ng/day (low dose: n = 6) and 500 ng/day (high dose: n = 7) for 10 days into devices implanted s.c. in Sprague-Dawley rats; noninfused devices transplanted for an identical period were used as controls (n = 5). Two days following the termination of VEGF infusion, devices were loaded with 20 microl of Lispro insulin (1 U/kg) and the kinetics of insulin release from the lumen of the device was assessed. Devices were then explanted and the number of blood vessels (capillary and noncapillary) was quantified using morphometry. High-dose vascular endothelial growth factor infusion resulted in two- to threefold more blood vessels around the device than that obtained with the noninfused devices and devices infused with low-dose vascular endothelial growth factor. This increase in the number of blood vessels was accompanied by a modest increase in insulin diffusion from the device in the high-dose vascular endothelial growth factor infusion group. We conclude that vascular endothelial growth factor can be used to improve blood vessel formation adjacent to planar membrane diffusion devices.

Zinc as a paracrine effector in pancreatic islet cell death.

PubMed

Kim, B J; Kim, Y H; Kim, S; Kim, J W; Koh, J Y; Oh, S H; Lee, M K; Kim, K W; Lee, M S

2000-03-01

Because of a huge amount of Zn2+ in secretory granules of pancreatic islet beta-cells, Zn2+ released in certain conditions might affect the function or survival of islet cells. We studied potential paracrine effects of endogenous Zn2+ on beta-cell death. Zn2+ induced insulinoma/islet cell death in a dose-dependent manner. Chelation of released endogenous Zn2+ by CaEDTA significantly decreased streptozotocin (STZ)-induced islet cell death in an in vitro culture system simulating in vivo circumstances but not in the conventional culture system. Zn2+ chelation in vivo by continuous CaEDTA infusion significantly decreased the incidence of diabetes after STZ administration. N-(6-methoxy-quinolyl)-para-toluene-sulfonamide staining revealed that Zn2+ was densely deposited in degenerating islet cells 24 h after STZ treatment, which was decreased by CaEDTA infusion. We show here that Zn2+ is not a passive element for insulin storage but an active participant in islet cell death in certain conditions, which in time might contribute to the development of diabetes in aged people.

Successful reinstitution of agalsidase beta therapy in Fabry disease patients with previous IgE-antibody or skin-test reactivity to the recombinant enzyme.

PubMed

Bodensteiner, David; Scott, C Ronald; Sims, Katherine B; Shepherd, Gillian M; Cintron, Rebecca D; Germain, Dominique P

2008-05-01

To determine if enzyme replacement therapy, involving intravenous infusions of recombinant human alpha-galactosidase A (agalsidase beta; Fabrazyme), could be safely continued in patients with Fabry disease who had been withdrawn from a previous clinical trial as a precautionary, protocol-specified measure due to detection of serum IgE antibodies or skin-test reactivity to agalsidase beta. The rechallenge infusion protocol specified strict patient monitoring conditions and graded dosing and infusion-rate schemes that were adjusted according to each patient's tolerance to the infusion. Six males (age: 26-66 years) were enrolled. During rechallenge, five patients received between 4 and 27 infusions; one patient voluntarily withdrew after one infusion because of recurrence of infusion-associated reactions. No anaphylactic reactions occurred. All adverse events, including four serious adverse events, were mild or moderate in intensity. Most treatment-related adverse events occurred during infusions (most commonly urticaria, vomiting, nausea, chills, pruritus, hypertension) and were resolved by infusion rate reductions and/or medication. After participation in the study, all patients, including the one who withdrew after one infusion, transitioned to commercial drug. Agalsidase beta therapy can be successfully reinstated in patients with Fabry disease who have developed IgE antibodies or skin test reactivity to the recombinant enzyme.

Connecting Research and Practice: An Experience Report on Research Infusion with SAVE

NASA Technical Reports Server (NTRS)

Lindvall, Mikael; Stratton, William C.; Sibol, Deane E.; Ackermann, Christopher; Reid, W. Mark; Ganesan, Dharmalingam; McComas, David; Bartholomew, Maureen; Godfrey, Sally

2009-01-01

NASA systems need to be highly dependable to avoid catastrophic mission failures. This calls for rigorous engineering processes including meticulous validation and verification. However, NASA systems are often highly distributed and overwhelmingly complex, making the software portion of these systems challenging to understand, maintain, change, reuse, and test. NASA's systems are long-lived and the software maintenance process typically constitutes 60-80% of the total cost of the entire lifecycle. Thus, in addition to the technical challenges of ensuring high life-time quality of NASA's systems, the post-development phase also presents a significant financial burden. Some of NASA's software-related challenges could potentially be addressed by some of the many powerful technologies that are being developed in software research laboratories. Many of these research technologies seek to facilitate maintenance and evolution by for example architecting, designing and modeling for quality, flexibility, and reuse. Other technologies attempt to detect and remove defects and other quality issues by various forms of automated defect detection, architecture analysis, and various forms of sophisticated simulation and testing. However promising, most such research technologies nevertheless do not make the transition from the research lab to the software lab. One reason the transition from research to practice seldom occurs is that research infusion and technology transfer is difficult. For example, factors related to the technology are sometimes overshadowed by other types of factors such as reluctance to change and therefore prohibits the technology from sticking. Successful infusion might also take very long time. One famous study showed that the discrepancy between the conception of the idea and its practical use was 18 years plus or minus three. Nevertheless, infusing new technology is possible. We have found that it takes special circumstances for such research infusion to succeed: 1) there must be evidence that the technology works in the practitioner's particular domain, 2) there must be a potential for great improvements and enhanced competitive edge for the practitioner, 3) the practitioner has to have strong individual curiosity and continuous interest in trying out new technologies, 4) the practitioner has to have support on multiple levels (i.e. from the researchers, from management, from sponsors etc), and 5) to remain infused, the new technology has to be integrated into the practitioner's processes so that it becomes a natural part of the daily work. NASA IV&V's Research Infusion initiative sponsored by NASA's Office of Safety & Mission Assurance (OSMA) through the Software Assurance Research Program (SARP), strives to overcome some of the problems related to research infusion.

Effect of blood flow on near-the-wall mass transport of drugs and other bioactive agents: a simple formula to estimate boundary layer concentrations.

PubMed

Rugonyi, Sandra

2008-04-01

Transport of bioactive agents through the blood is essential for cardiovascular regulatory processes and drug delivery. Bioactive agents and other solutes infused into the blood through the wall of a blood vessel or released into the blood from an area in the vessel wall spread downstream of the infusion/release region and form a thin boundary layer in which solute concentration is higher than in the rest of the blood. Bioactive agents distributed along the vessel wall affect endothelial cells and regulate biological processes, such as thrombus formation, atherogenesis, and vascular remodeling. To calculate the concentration of solutes in the boundary layer, researchers have generally used numerical simulations. However, to investigate the effect of blood flow, infusion rate, and vessel geometry on the concentration of different solutes, many simulations are needed, leading to a time-consuming effort. In this paper, a relatively simple formula to quantify concentrations in a tube downstream of an infusion/release region is presented. Given known blood-flow rates, tube radius, solute diffusivity, and the length of the infusion region, this formula can be used to quickly estimate solute concentrations when infusion rates are known or to estimate infusion rates when solute concentrations at a point downstream of the infusion region are known. The developed formula is based on boundary layer theory and physical principles. The formula is an approximate solution of the advection-diffusion equations in the boundary layer region when solute concentration is small (dilute solution), infusion rate is modeled as a mass flux, and there is no transport of solute through the wall or chemical reactions downstream of the infusion region. Wall concentrations calculated using the formula developed in this paper were compared to the results from finite element models. Agreement between the results was within 10%. The developed formula could be used in experimental procedures to evaluate drug efficacy, in the design of drug-eluting stents, and to calculate rates of release of bioactive substances at active surfaces using downstream concentration measurements. In addition to being simple and fast to use, the formula gives accurate quantifications of concentrations and infusion rates under steady-state and oscillatory flow conditions, and therefore can be used to estimate boundary layer concentrations under physiological conditions.

Intracerebroventricular morphine for refractory cancer pain: transitioning to the home setting.

PubMed

Adolph, Michael D; Stretanski, Michael F; McGregor, John M; Rawn, Bonnie L; Ross, Patrick M; Benedetti, Costantino

2010-08-01

Refractory cancer pain may be effectively controlled by titrating intracerebroventricular (ICV) preservative-free opioid. In this case report, a continuous infusion of ICV morphine permitted our patient with lung cancer and painful spinal metastases to be discharged to home hospice with family. The approach exploits the high potency of morphine injected into cerebrospinal fluid (CSF). Sterile, injectable, preservative-free morphine is directly infused into CSF through a subcutaneous Ommaya reservoir placed under the scalp by a neurosurgeon, with an attached catheter passed through a burr hole in the skull with its tip in a cerebral ventricle. Although investigators have described home care of patients receiving intraspinal analgesics, no report describes the process of transitioning the patient receiving continuous ICV morphine infusion to the home setting.

Superselective Urokinase Infusion Therapy for Dorsalis Pedis Artery Occlusion in Buerger's Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kubota, Yasushi; Kichikawa, Kimihiko; Uchida, Hideo

1997-09-15

Occlusion of the proximal left dorsalis pedis artery (DPA) in a patient with Buerger's disease was treated by continuous urokinase intraarterial infusion using a microcatheter. Recanalization of the DPA and healing of a toe ulcer were achieved. The patient remains asymptomatic during a 4-year follow-up.

[A case of coronary artery spasm during epidural anesthesia with continuous infusion of propofol].

PubMed

Inoue, Hisashi; Ogawa, Katsumi; Takano, Yoshito; Sato, Isao; Okuda, Yasuhisa

2003-07-01

A 50-year-old male patient was scheduled for left partial pulmonary resection and biopsy. The patient had neither complication nor history of ischemic heart disease. After arriving in the operation room, an epidural catheter was inserted into the epidural space at the T 4-5 intervertebral space. Anesthesia was induced with intravenous propofol 100 mg, fentanyl 100 microgram and vecuronium 6 mg and then a double lumen endotracheal tube was inserted. Anesthesia was maintained with O2 and air (FIO2 0.3-1.0), continuous infusion of propofol, intermittent intravenous administration of fentanyl and epidural injection of 1% lidocaine. Forty-five minutes after the start of operation, ECG showed an elevation of ST segment and soon it passed into ventricular tachycardia and ventricular fibrillation. The patient was treated with cardiopulmonary resuscitation. Fifteen minutes later, ECG returned to sinus rhythm but the elevation of ST segment remained. We considered that these cardiac events were due to coronary spasm, and started continuous infusion of nitroglycerin and nicorandil. One hour later, ST segment returned to normal. The possible inducing factors in this case were altered balance between sympathetic and parasympathetic nervous activity caused by infusion of propofol and epidural block, and alpha-stimulation caused by ephedrine.

Continuous intra-arterial 5-FU chemotherapy in a patient with a repeated recurrence of rectal cancer: report of a case.

PubMed

Toh, U; Isomoto, H; Araki, Y; Matsumoto, A; Yasunaga, M; Ogoh, Y; Inuzuka, K; Ozaki, K; Shirouzu, K

2000-06-01

We report a patient with a recurrent pelvic tumor after abdominoperineal resection of a rectal carcinoma who was treated sufficiently by repeated intra-arterial infusions of 5-fluorouracil. A continuous, 24-hour 5-fluorouracil administration was made through the bilateral internal iliac artery at a dosage of 250 mg/m2/day by the subcutaneous reservoir located at both upper legs using a Baxter infusor. In this patient pain in the hip and pelvis was relieved. A complete regression in the infused field of pelvic tumor was observed not only with computed tomography and magnetic resonance imaging but also confirmed by operative findings at the seventh month after the intra-arterial infusion. The abnormal serum level of carcinoembryonic antigen and carbohydrate antigen 19-9 was decreased to within the normal range at the 19th and 3rd week respectively. When the repeated recurrence was suspected in follow-up, normalization of the re-elevated carcinoembryonic antigen and carbohydrate antigen 19-9 levels was also obtained by repeating the same treatment. The side effects and complications were tolerable, consisting of local skin erosion on the hips and lower extremity neuropathy caused by the 5-fluorouracil. Clinical local regression of a pelvic recurrence was observed in a patient with rectal recurrent tumor who received continuous intra-arterial chemotherapy. Local recurrence of rectal cancer may be controlled effectively and safely by repeating long-term, continuous, intra-arterial 5-fluorouracil infusion.

Pascal's wager: combining continuous glucose monitoring and continuous subcutaneous insulin infusion.

PubMed

Kerr, David; Olateju, Tolu

2010-06-01

Pascal's Wager is a suggestion posed by the French Philosopher, Blaise Pascal, that even though the existence of God cannot be determined through reason, a person should wager that God exists because he or she has everything to gain and nothing to lose. In the area of consideration here, the optimum experimental trial of the combined use of continuous subcutaneous insulin infusion and real-time continuous glucose monitoring in free-living individuals with type 1 diabetes providing rock-solid evidence of clinical benefit has not been performed. Nevertheless, there is considerable enthusiasm for combining the technologies among healthcare professionals, patients, and manufacturers based on the belief that this approach to diabetes care must be beneficial beyond the available evidence (i.e., reason).

Quality-improvement analytics for intravenous infusion pumps.

PubMed

Skledar, Susan J; Niccolai, Cynthia S; Schilling, Dennis; Costello, Susan; Mininni, Nicolette; Ervin, Kelly; Urban, Alana

2013-04-15

The implementation of a smart-pump continuous quality-improvement (CQI) program across a large health system is described, with an emphasis on key metrics for outcomes analyses and program refinement. Three years ago, the University of Pittsburgh Medical Center health system launched a CQI initiative to help ensure the safe use of 6000 smart pumps in its 14 inpatient facilities. A centralized team led by pharmacists is responsible for the retrieval and interpretation of smart-pump data, which is continuously transmitted to a main server. CQI findings are regularly posted on the health system's interdisciplinary intranet. Monitored metrics include rates of compliance with preprogrammed infusion limits, the top 20 drugs involved in alerts, drugs associated with alert-override rates of ≥90%, numbers of alerts by infusion type, nurse responses to alerts, and alert rate per drug library update. Based on the collected CQI data and site-specific requests, four systemwide updates of the smart-pump drug library were performed during the first 18 months of the program, reducing "nuisance alerts" by about 10% per update cycle and enabling targeted interventions to reduce rapid-infusion errors, other adverse drug events (ADEs), and pump-programming workarounds. Over one 12-month period, bedside alerts prompted nurses to reprogram or cancel continuous infusions an average of 400 times per month, potentially averting i.v. medication ADEs. A smart-pump CQI program is an effective tool for enhancing the safety of i.v. medication administration. The ongoing refinement of the drug library through the development and implementation of key interventions promotes the growth and sustainability of the smart-pump initiative systemwide.

Tissue distribution of sup 3 H-nicotine in rats after bolus or constant injection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chowdhury, P.; Pasley, J.N.; Rayford, P.L.

1989-01-01

Two groups of rats, (N = 7), were fasted for 24 hrs prior to the study. On the day of the experiment, the animals were anesthetized and infused with either 5 ml nicotine solution (200 {mu}g/L) in saline containing 5 {mu}c {sup 3}H-nicotine, (sp. activity 50-80 mCi/mol) for 90 minutes or injected as a bolus with 0.5 ml of the same nicotine (200 {mu}g/L) solution. The animals were sacrificed 60 minutes after the injection or after the infusion was stopped. Blood and tissue samples were counted by liquid scintillation counting. Percent distribution of {sup 3}H-nicotine per gm of tissue wasmore » calculated from the total radioactivity recovered in individual tissues over the total activity injected into the rat and the values were compared using student's t test. Results: Distribution of {sup 3}H-nicotine was found highest in kidney (45-49%) among all tissues examined and was not different between routes of administration. Significantly higher retention of {sup 3}H-nicotine was found with continuous infusion in esophagus, fundus, antrum, spleen, cecum, pancreas, testes, heart and muscle when {sup 3}H-nicotine retentions were compared with bolus injection. In contrast, the distribution of {sup 3}H-nicotine in adrenal gland, was significantly lower in continuous infusion group. Distribution in blood was 6 fold higher in continuous infusion (7.26%) compared to bolus (1.11%) injection. The distribution {sup 3}H-nicotine in other tissues were not different by either routes of injection.« less

Model-based verification and validation of the SMAP uplink processes

NASA Astrophysics Data System (ADS)

Khan, M. O.; Dubos, G. F.; Tirona, J.; Standley, S.

Model-Based Systems Engineering (MBSE) is being used increasingly within the spacecraft design community because of its benefits when compared to document-based approaches. As the complexity of projects expands dramatically with continually increasing computational power and technology infusion, the time and effort needed for verification and validation (V& V) increases geometrically. Using simulation to perform design validation with system-level models earlier in the life cycle stands to bridge the gap between design of the system (based on system-level requirements) and verifying those requirements/validating the system as a whole. This case study stands as an example of how a project can validate a system-level design earlier in the project life cycle than traditional V& V processes by using simulation on a system model. Specifically, this paper describes how simulation was added to a system model of the Soil Moisture Active-Passive (SMAP) mission's uplink process. Also discussed are the advantages and disadvantages of the methods employed and the lessons learned; which are intended to benefit future model-based and simulation-based development efforts.

Transcriptomic Impacts of Rumen Epithelium Induced by Butyrate Infusion in Dairy Cattle in Dry Period

PubMed Central

Baldwin, Ransom L; Li, Robert W; Jia, Yankai; Li, Cong-Jun

2018-01-01

The purpose of this study was to evaluate the effects of butyrate infusion on rumen epithelial transcriptome. Next-generation sequencing (NGS) and bioinformatics are used to accelerate our understanding of regulation in rumen epithelial transcriptome of cattle in the dry period induced by butyrate infusion at the level of the whole transcriptome. Butyrate, as an essential element of nutrients, is a histone deacetylase (HDAC) inhibitor that can alter histone acetylation and methylation, and plays a prominent role in regulating genomic activities influencing rumen nutrition utilization and function. Ruminal infusion of butyrate was following 0-hour sampling (baseline controls) and continued for 168 hours at a rate of 5.0 L/day of a 2.5 M solution as a continuous infusion. Following the 168-hour infusion, the infusion was stopped, and cows were maintained on the basal lactation ration for an additional 168 hours for sampling. Rumen epithelial samples were serially collected via biopsy through rumen fistulae at 0-, 24-, 72-, and 168-hour (D1, D3, D7) and 168-hour post-infusion (D14). In comparison with pre-infusion at 0 hours, a total of 3513 genes were identified to be impacted in the rumen epithelium by butyrate infusion at least once at different sampling time points at a stringent cutoff of false discovery rate (FDR) < 0.01. The maximal effect of butyrate was observed at day 7. Among these impacted genes, 117 genes were responsive consistently from day 1 to day 14, and another 42 genes were lasting through day 7. Temporal effects induced by butyrate infusion indicate that the transcriptomic alterations are very dynamic. Gene ontology (GO) enrichment analysis revealed that in the early stage of rumen butyrate infusion (on day 1 and day 3 of butyrate infusion), the transcriptomic effects in the rumen epithelium were involved with mitotic cell cycle process, cell cycle process, and regulation of cell cycle. Bioinformatic analysis of cellular functions, canonical pathways, and upstream regulator of impacted genes underlie the potential mechanisms of butyrate-induced gene expression regulation in rumen epithelium. The introduction of transcriptomic and bioinformatic technologies to study nutrigenomics in the farm animal presented a new prospect to study multiple levels of biological information to better apprehend the whole animal response to nutrition, physiological state, and their interactions. The nutrigenomics approach may eventually lead to more precise management of utilization of feed resources in a more effective approach. PMID:29785087

Feasibility of dose enhancement assessment: Preliminary results by means of Gd-infused polymer gel dosimeter and Monte Carlo study.

PubMed

Santibáñez, M; Guillen, Y; Chacón, D; Figueroa, R G; Valente, M

2018-04-11

This work reports the experimental development of an integral Gd-infused dosimeter suitable for Gd dose enhancement assessment along with Monte Carlo simulations applied to determine the dose enhancement by radioactive and X-ray sources of interest in conventional and electronic brachytherapy. In this context, capability to elaborate a stable and reliable Gd-infused dosimeter was the first goal aimed at direct and accurate measurements of dose enhancement due to Gd presence. Dose-response was characterized for standard and Gd-infused PAGAT polymer gel dosimeters by means of optical transmission/absorbance. The developed Gd-infused PAGAT dosimeters demonstrated to be stable presenting similar dose-response as standard PAGAT within a linear trend up to 13 Gy along with good post-irradiation readout stability verified at 24 and 48 h. Additionally, dose enhancement was evaluated for Gd-infused PAGAT dosimeters by means of Monte Carlo (PENELOPE) simulations considering scenarios for isotopic and X-ray generator sources. The obtained results demonstrated the feasibility of obtaining a maximum enhancement around of (14 ± 1)% for 192 Ir source and an average enhancement of (70 ± 13)% for 241 Am. However, dose enhancement up to (267 ± 18)% may be achieved if suitable filtering is added to the 241 Am source. On the other hand, optimized X-ray spectra may attain dose enhancements up to (253 ± 22) %, which constitutes a promising future alternative for replacing radioactive sources by implementing electronic brachytherapy achieving high dose levels. Copyright © 2018. Published by Elsevier Ltd.

[Clinical study of recurrent stomach cancer].

PubMed

Taguchi, T

1983-11-01

There are various patterns of recurrence of gastric cancer after radical resection, such as hepatic metastasis, carcinomatous peritonitis, residual stomach recurrence, local lymph node metastasis and establishment of distant metastasis. In cases of residual stomach recurrence, resection is sometimes feasible. Kruckenberg's tumor resulting from metastasis to the ovary can frequently be removed. With such resectable metastasis, surgical procedure is actively employed, with subsequent chemotherapy. Chemotherapy in such a case consists of combined chemotherapy by arterial infusion for induction of remission and administration of oral preparation and/or suppositories for maintenance. In the treatment of recurrent gastric cancer by arterial infusion, we made it a rule to administer drugs through a catheter inserted subselectively into the aorta. In the treatment by arterial infusion, the daily administration of 5-FU serves as the basic regimen. Dissolve 250 mg 5-FU in about 20 cc physiologic saline or 5% dextrose solution, and infuse the solution over 2 hrs with the use of a continuous arterial infusion pump. Administer of 5-FU daily, and fortify this treatment by one-shot injection of MMC 10mg/body each time, MMC is usually given 3-4 times, with intervals between its administrations adjusted according to WBC and platelet counts. ADM is given at dosage of 40 mg/body each time. We found it advisable to continue the administrations of 5-FU until its total dose reached about 20 g, while giving sufficient doses of ADM or MMC for induction of remission. The results obtained from 108 cases of the recurrent gastric cancer were shown as follows. The median survival period was 5 months. The twenty-one cases out of 108 cases in recurrent gastric cancer survived more than one year, because they received the intensive chemotherapy such as arterial infusion chemotherapy and oral or rectal administration of FT. The most patients with liver metastasis were treated with selective arterial infusion chemotherapy consisting of 5-FU plus MMC or ACNU. And the efficacy of arterial infusion chemotherapy was remarkable. Our efforts must be made to continue any treatment as long as possible and change drugs as necessary. Also we must keep general condition of the patients as good as possible using support therapy such as IVH, prevention of infection, immunotherapy, drainage so on.

The Influence of Insulin Injections and Infusions on Eating and Blood Glucose Level in the Rat,

DTIC Science & Technology

then a sudden rise ensues. Continuous infusion of insulin in normal rats induces hyperphagia : blood glucose decreases slowly to 50 mg%; at which...insulin into static obese hypothalamic subjects (whose daily food intake is fairly normal) leads to renewed hyperphagia , but the fluctuations in blood

Long-term leucine induced stimulation of muscle protein synthesis is amino acid dependent

USDA-ARS?s Scientific Manuscript database

Infusing leucine for 1 h increases skeletal muscle protein synthesis in the neonate, but this is not sustained for 2 h unless the corresponding fall in amino acids is prevented. This study aimed to determine whether a continuous leucine infusion can stimulate protein synthesis for a prolonged period...

Growth Infusion: Embedding Staff Development in a Culture of Learning

ERIC Educational Resources Information Center

Bennett, Betty J.

2017-01-01

To address increasing accountability demands, instructional leaders must find ways to expand the current reality of faculty development to create a culture where continuous growth and learning are the standard for professional behavior. Growth Infusion is a framework for creating such a culture. The framework is a result of an extensive search for…

Severe infusion reactions to fabry enzyme replacement therapy: rechallenge after tracheostomy.

PubMed

Nicholls, K; Bleasel, K; Becker, G

2012-01-01

A 34-year-old male patient with Fabry disease (OMIM 301500) commenced enzyme replacement therapy (ERT) with Agalsidase alfa, with positive clinical response. Infusion reactions, initially mild and easily managed, commenced during his 13th infusion, and continued over the next 3 years. Severity of reactions subsequently increased despite very slow infusion, extended prophylactic medication and attempted desensitisation, requiring regular intensive care unit (ICU) admissions. Facial oedema and flushing, throat tightness, headache and joint pain typically occurred 4-36 h after completion of most infusions, responding rapidly to subcutaneous adrenaline. Low titre specific IgG seroconversion was noted at 12 months, with subsequent reversion to negative after 5 years, despite persistence of infusion reactions. Specific IgE and skin testing was negative. Trial of ERT product switch to Agalsidase-beta resulted in no improvement in reactions. At 5 years, ERT was ceased in the face of recurrent ICU readmissions. In the face of progressive clinical deterioration, he underwent tracheostomy to allow recommencement of ERT. Two years later, he has clinically improved on regular attenuated dose Agalsidase-beta, administered by slow infusion in a local hospital setting.

A North Central Cancer Treatment Group Phase II trial of 9-aminocamptothecin in previously untreated patients with measurable metastatic colorectal carcinoma.

PubMed

Pitot, H C; Knost, J A; Mahoney, M R; Kugler, J; Krook, J E; Hatfield, A K; Sargent, D J; Goldberg, R M

2000-10-15

Topoisomerase I inhibitors have demonstrated clinical activity in patients with metastatic colorectal carcinoma. The authors performed a Phase II study to evaluate the objective tumor response rate of 2 different doses and schedules of 9-aminocamptothecin (9-AC) in previously untreated patients with measurable recurrent metastatic colorectal carcinoma. Fifty-one patients were registered. One schedule evaluated 9-AC given at 1100 microgram/m(2)/24 hours by continuous infusion for 72 hours along with granulocyte-colony stimulating factor at 5 microgram/kg/day on Days 5 through 12. Another schedule involved 9-AC at 480 microgram/m(2)/24 hours by continuous infusion for 120 hours on Days 1, 8, and 15 given every 4 weeks. Forty-eight of 51 patients (94%) were evaluable (28 patients who received 72-hour infusion and 20 patients who received 120-hour infusion) for response and toxicity. Significant hematologic toxicities were encountered, especially with the 72-hour infusion schedule, in which 43% (12 of 28) and 28% (8 of 28) experienced Grade 4 (National Cancer Institute Common Toxicity Criteria) leukopenia and thrombocytopenia, respectively. Grade 4 neutropenia was encountered in 61% (17 of 28) and 11% (2 of 19) of patients on the 72-hour and 120-hour infusion schedules, respectively. Diarrhea, nausea, vomiting, and hepatotoxicity were troublesome nonhematologic toxicities. Seventy-nine percent (11 of 14) and 57% (4 of 7) of the patients experiencing Grade 3 or 4 nonhematologic toxicity were on the 72-hour infusion schedule. Three patients died of chemotherapy-related toxicity. One response was observed in 48 evaluable patients (2%). 9-AC did not demonstrate sufficient antitumor activity and had unacceptable toxicity in previously untreated patients with metastatic colorectal carcinoma. Copyright 2000 American Cancer Society.

Management of life-threatening calcium channel blocker overdose with continuous veno-venous hemodiafiltration with charcoal hemoperfusion

PubMed Central

Garg, Suneel K.; Goyal, Pankaj K.; Kumar, Rahul; Juneja, Deven; Bhasin, Alka; Singh, Omender

2014-01-01

Cases of calcium channel blocker overdose reported from India are few, and although rare, they are associated with high mortality. Management includes fluids, vasopressors, calcium gluconate or chloride, glucagon infusion, and hyperinsulinemia-euglycemia therapy along with some rescue therapies tried in anecdotal reports. We report here a case of life-threatening overdose of amlodipine with shock, refractory to conventional therapies. Salvage therapy with continuous veno-venous hemodiafiltration using charcoal hemoperfusion with prior infusion of intravenous lipid emulsion resulted in a successful outcome. PMID:24987241

Circadian hormone profiles and insulin sensitivity in patients with Addison's disease: a comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy.

PubMed

Björnsdottir, Sigridur; Øksnes, Marianne; Isaksson, Magnus; Methlie, Paal; Nilsen, Roy M; Hustad, Steinar; Kämpe, Olle; Hulting, Anna-Lena; Husebye, Eystein S; Løvås, Kristian; Nyström, Thomas; Bensing, Sophie

2015-07-01

Conventional glucocorticoid replacement therapy in patients with Addison's disease (AD) is unphysiological with possible adverse effects on mortality, morbidity and quality of life. The diurnal cortisol profile can likely be restored by continuous subcutaneous hydrocortisone infusion (CSHI). The aim of this study was to compare circadian hormone rhythms and insulin sensitivity in conventional thrice-daily regimen of glucocorticoid replacement therapy with CSHI treatment in patients with AD. An open, randomized, two-period, 12-week crossover multicentre trial in Norway and Sweden. Ten Norwegian patients were admitted for 24-h sampling of hormone profiles. Fifteen Swedish patients underwent euglycaemic-hyperinsulinaemic clamp. Thrice-daily regimen of oral hydrocortisone (OHC) and CSHI treatment. We measured the circadian rhythm of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH), insulin-like growth factor-1, (IGF-1), IGF-binding protein-3 (IGFBP-3), glucose, insulin and triglycerides during OHC and CSHI treatment. Euglycaemic-hyperinsulinaemic clamp was used to assess insulin sensitivity. Continuous subcutaneous hydrocortisone infusion provided a more physiological circadian cortisol curve including a late-night cortisol surge. ACTH levels showed a near normal circadian variation for CSHI. CSHI prevented a continuous decrease in glucose during the night. No difference in insulin sensitivity was observed between the two treatment arms. Continuous subcutaneous hydrocortisone infusion replacement re-established a circadian cortisol rhythm and normalized the ACTH levels. Patients with CSHI replacement had a more stable night-time glucose level compared with OHC without compromising insulin sensitivity. Thus, restoring night-time cortisol levels might be advantageous for patients with AD. © 2015 John Wiley & Sons Ltd.

Chronic intracerebroventricular infusion of nociceptin/orphanin FQ increases food and ethanol intake in alcohol-preferring rats.

PubMed

Cifani, Carlo; Guerrini, Remo; Massi, Maurizio; Polidori, Carlo

2006-11-01

Central administration of low doses of nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the opioid-like orphan receptor NOP, have been shown to reduce ethanol consumption, ethanol-induced conditioned place preference and stress-induced reinstatement of alcohol-seeking behavior in alcohol preferring rats. The present study evaluated the effect of continuous (7 days) lateral brain ventricle infusions of N/OFQ (0, 0.25, 1, 4, and 8 microg/h), by means of osmotic mini-pumps, on 10% ethanol intake in Marchigian-Sardinian alcohol-preferring (msP) rats provided 2h or 24h access to it. N/OFQ dose-dependently increased food intake in msP rats. On the other hand, in contrast to previous studies with acute injections, continuous lateral brain ventricle infusion of high doses of N/OFQ increased ethanol consumption when the ethanol solution was available for 24h/day or 2h/day. The present study demonstrates that continuous activation of the opioidergic N/OFQ receptor does not blunt the reinforcing effects of ethanol. Moreover, the data suggest that continuous activation of the opioidergic N/OFQ receptor is not a suitable way to reduce alcohol abuse.

A study of estrogen metabolic clearance rates and transfer factors

PubMed Central

Hembree, W. C.; Bardin, C. W.; Lipsett, M. B.

1969-01-01

We have attempted to measure the metabolic clearance rates (MCR) and the transfer factors of estradiol (E2) and estrone (E1) during 2-hr and 12-hr infusions. When estradiol-3H was infused for 2 hr, apparent equilibrium was reached at 70 min; the 12-hr infusions showed that plasma estradiol-3H levels increased slowly throughout the infusion. When estrone-3H was infused, constancy of estrone-3H levels was not attained in either the 2-hr infusions or in the two 12-hr infusions. The tritium level in the metabolite of the infused estrogen did not become constant in 50% of the short infusions and increased during all the long infusions. Thus, the conversion ratios CE1E2 and CE2E1 continually changed and transfer factors could not be calculated. The apparent “MCR'S” calculated on the basis of the 2-hr studies expressed as liters/24 hr per m2 ±SD were: “MCRE1” (women) 980 ±94, (men) 1170 ±95; “MCRE2” (women) 615 ±17, (men) 830 ±30. The estradiol “MCR's” differed significantly between men and women. “MCRE2” was the same using either estradiol-14C or -3H and was unchanged by the infusion of 170 μg of estradiol daily. Postmenopausal women had estrogen “MCR's” in the same range as premenopausal women. Excess glucocorticoids increased the “MCRE2.” PMID:5822587

Mathematical Modelling of the Infusion Test

NASA Astrophysics Data System (ADS)

Cieslicki, Krzysztof

2007-01-01

The objective of this paper was to improve the well established in clinical practice Marmarou model for intracranial volume-pressure compensation by adding the pulsatile components. It was demonstrated that complicated pulsation and growth in intracranial pressure during infusion test could be successfully modeled by the relatively simple analytical expression derived in this paper. The CSF dynamics were tested in 25 patients with clinical symptoms of hydrocephalus. Basing on the frequency spectrum of the patient's baseline pressure and identified parameters of CSF dynamic, for each patient an "ideal" infusion test curve free from artefacts and slow waves was simulated. The degree of correlation between simulated and real curves obtained from clinical observations gave insight into the adequacy of assumptions of Marmarou model. The proposed method of infusion tests analysis designates more exactly the value of the reference pressure, which is usually treated as a secondary and of uncertain significance. The properly identified value of the reference pressure decides on the degree of pulsation amplitude growth during IT, as well as on the value of elastance coefficient. The artificially generated tests with various pulsation components were also applied to examine the correctness of the used algorithm of identification of the original Marmarou model parameters.

Banting Memorial Lecture 2014* Technology and diabetes care: appropriate and personalized.

PubMed

Pickup, J C

2015-01-01

Continuous subcutaneous insulin infusion was initially developed as a research procedure in the 1970s but quickly became a routine treatment for selected people with Type 1 diabetes. Continuous subcutaneous insulin infusion and other diabetes technologies, such as continuous glucose monitoring, are now an established and evidence-based part of diabetes care, but there has been some confusion about effectiveness and best use, particularly because of conflicting results from meta-analyses. This is because literature summary meta-analyses (including all trials) are inappropriate for therapeutic and economic decision-making; such meta-analyses should only include trials representative of groups likely to benefit. For example, for continuous subcutaneous insulin infusion, this would be those with continued disabling hypoglycaemia or elevated HbA1c levels. Alternatively, individual patient data meta-analysis allows modelling of covariates that determine effect size, e.g. in the case of continuous glucose monitoring, baseline HbA1c and frequency of sensor usage. Diabetes technology is therefore an example of personalized medicine, where evaluation and use should be both appropriate and targeted. This will also apply to future technologies such as new 'patch' pumps for Type 2 diabetes, closed-loop insulin delivery systems and nanomedicine applications in diabetes that we are currently researching. These include fluorescence lifetime-based non-invasive glucose monitoring and nanoencapsulation of islets for improved post-transplant survival. © 2014 The Author. Diabetic Medicine © 2014 Diabetes UK.

Diabetes Technology-Continuous Subcutaneous Insulin Infusion Therapy and Continuous Glucose Monitoring in Adults: An Endocrine Society Clinical Practice Guideline.

PubMed

Peters, Anne L; Ahmann, Andrew J; Battelino, Tadej; Evert, Alison; Hirsch, Irl B; Murad, M Hassan; Winter, William E; Wolpert, Howard

2016-11-01

To formulate clinical practice guidelines for the use of continuous glucose monitoring and continuous subcutaneous insulin infusion in adults with diabetes. The participants include an Endocrine Society-appointed Task Force of seven experts, a methodologist, and a medical writer. The American Association for Clinical Chemistry, the American Association of Diabetes Educators, and the European Society of Endocrinology co-sponsored this guideline. The Task Force developed this evidence-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned one systematic review and used the best available evidence from other published systematic reviews and individual studies. One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the American Association for Clinical Chemistry, the American Association of Diabetes Educators, and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Continuous subcutaneous insulin infusion and continuous glucose monitoring have an important role in the treatment of diabetes. Data from randomized controlled trials are limited on the use of medical devices, but existing studies support the use of diabetes technology for a wide variety of indications. This guideline presents a review of the literature and practice recommendations for appropriate device use.

An in silico method to identify computer-based protocols worthy of clinical study: An insulin infusion protocol use case

PubMed Central

Wong, Anthony F; Pielmeier, Ulrike; Haug, Peter J; Andreassen, Steen

2016-01-01

Objective Develop an efficient non-clinical method for identifying promising computer-based protocols for clinical study. An in silico comparison can provide information that informs the decision to proceed to a clinical trial. The authors compared two existing computer-based insulin infusion protocols: eProtocol-insulin from Utah, USA, and Glucosafe from Denmark. Materials and Methods The authors used eProtocol-insulin to manage intensive care unit (ICU) hyperglycemia with intravenous (IV) insulin from 2004 to 2010. Recommendations accepted by the bedside clinicians directly link the subsequent blood glucose values to eProtocol-insulin recommendations and provide a unique clinical database. The authors retrospectively compared in silico 18 984 eProtocol-insulin continuous IV insulin infusion rate recommendations from 408 ICU patients with those of Glucosafe, the candidate computer-based protocol. The subsequent blood glucose measurement value (low, on target, high) was used to identify if the insulin recommendation was too high, on target, or too low. Results Glucosafe consistently provided more favorable continuous IV insulin infusion rate recommendations than eProtocol-insulin for on target (64% of comparisons), low (80% of comparisons), or high (70% of comparisons) blood glucose. Aggregated eProtocol-insulin and Glucosafe continuous IV insulin infusion rates were clinically similar though statistically significantly different (Wilcoxon signed rank test P = .01). In contrast, when stratified by low, on target, or high subsequent blood glucose measurement, insulin infusion rates from eProtocol-insulin and Glucosafe were statistically significantly different (Wilcoxon signed rank test, P < .001), and clinically different. Discussion This in silico comparison appears to be an efficient nonclinical method for identifying promising computer-based protocols. Conclusion Preclinical in silico comparison analytical framework allows rapid and inexpensive identification of computer-based protocol care strategies that justify expensive and burdensome clinical trials. PMID:26228765

Implantation of programmable infusion pumps for insulin delivery in type I diabetic patients.

PubMed

Walter, H; Günther, A; Kronski, D; Flaschenträger, T; Mehnert, H

1989-06-01

Five type I diabetic patients were followed prospectively during treatment with continuous subcutaneous insulin infusion by externally worn pumps and during the first 12 months after implantation of a remote-controlled insulin infusion device (ID1, Siemens AG). Stabilized insulin (Hoe 21 GH, Hoechst AG) was infused intravenously in two and intraperitoneally in three patients. Total observation time was 47.2 patient-months after implantation. Two devices had to be explanted prematurely, one because of a technical failure after 101 days, one due to a skin necrosis over the implant after 236 days. HbA1, frequency of hypoglycemia, total insulin dose, and basal rate infusion did not change after implantation. There was a reduction in the insulin antibodies 6 months after start of intravenous or intraperitoneal insulin delivery. Fasting plasma free insulin levels could be normalized only by intraperitoneal insulin infusion. Although a technical and a surgical problem was observed, our data show the successful implantation and clinical use of programmable dosing devices and stabilized insulin.

A mechanistic model of small intestinal starch digestion and glucose uptake in the cow.

PubMed

Mills, J A N; France, J; Ellis, J L; Crompton, L A; Bannink, A; Hanigan, M D; Dijkstra, J

2017-06-01

The high contribution of postruminal starch digestion (up to 50%) to total-tract starch digestion on energy-dense, starch-rich diets demands that limitations to small intestinal starch digestion be identified. A mechanistic model of the small intestine was described and evaluated with regard to its ability to simulate observations from abomasal carbohydrate infusions in the dairy cow. The 7 state variables represent starch, oligosaccharide, glucose, and pancreatic amylase in the intestinal lumen, oligosaccharide and glucose in the unstirred water layer at the intestinal wall, and intracellular glucose of the enterocyte. Enzymatic hydrolysis of starch was modeled as a 2-stage process involving the activity of pancreatic amylase in the lumen and of oligosaccharidase at the brush border of the enterocyte confined within the unstirred water layer. The Na + -dependent glucose transport into the enterocyte was represented along with a facilitative glucose transporter 2 transport system on the basolateral membrane. The small intestine is subdivided into 3 main sections, representing the duodenum, jejunum, and ileum for parameterization. Further subsections are defined between which continual digesta flow is represented. The model predicted nonstructural carbohydrate disappearance in the small intestine for cattle unadapted to duodenal infusion with a coefficient of determination of 0.92 and a root mean square prediction error of 25.4%. Simulation of glucose disappearance for mature Holstein heifers adapted to various levels of duodenal glucose infusion yielded a coefficient of determination of 0.81 and a root mean square prediction error of 38.6%. Analysis of model behavior identified limitations to the efficiency of small intestinal starch digestion with high levels of duodenal starch flow. Limitations to individual processes, particularly starch digestion in the proximal section of the intestine, can create asynchrony between starch hydrolysis and glucose uptake capacity. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Professional ethics. A case study of infusion nurse consultants.

PubMed

Adams, J

2000-01-01

As the healthcare system continues to reform, opportunities exist for infusion nurses to expand their practice into the business world. Traditionally, biomedical ethics have been used in nursing education as a framework for identifying and responding to ethical dilemmas. However, in the business world, professional ethics may be more subtle and insidious. A case study of ten infusion nurse consultants and their experiences with professional ethical issues is presented. Data were obtained using interviews, and content analysis revealed emergent themes of integrity and intuitive knowing with related categories.

Does growth hormone releasing factor desensitize the somatotroph? Interpretation of responses of growth hormone during and after 10-hour infusion of GRF 1-29 amide in man.

PubMed

Davis, J R; Sheppard, M C; Shakespear, R A; Lynch, S S; Clayton, R N

1986-02-01

It is unclear whether growth hormone releasing factor (GRF) administration in vivo may desensitize the somatotroph. To investigate this possibility we have examined the effects of 10-h infusion of the equipotent 1-29 amide analogue of hpGRF on serum GH levels and on the subsequent GH response to a bolus dose of GRF (1-29). Four normal adult males received an intravenous infusion of 1-29 GRF (1 microgram/kg/h) from 0800 to 1800 h, with blood samples taken at 10 min intervals. A 100 micrograms intravenous bolus dose of GRF was given at 1800 h, and sampling continued for a further 90 min. GH levels were near or below the limit of detection (0.5 mU/l) throughout the control 10 h period. During GRF infusion there was increased GH release with pulses of irregular frequency and amplitude (up to 80 mU/l) continuing throughout the entire infusion period. There was no apparent reduction in total GH released towards the latter part of the infusion. On the control day, 100 micrograms GRF bolus increased mean (+/- SEM) GH from 0.82 +/- 0.21 mU/l to a peak of 59.0 +/- 44.8 mU/l (P less than 0.002). Following 10-GRF infusion, responses to bolus injection of GRF were reduced, but variable. In two subjects a small rise in GH levels occurred (basal 6.4 and 7.2 rising to peak values of 11.2 and 23.0 mU/l respectively). In the other two subjects, GH levels fell but in these the GRF bolus had coincided with a GH peak. The loss of GRF responsiveness after GRF infusion may be due to 'desensitization'.(ABSTRACT TRUNCATED AT 250 WORDS)

Association between continuous peripheral i.v. infusion of 3% sodium chloride injection and phlebitis in adults.

PubMed

Meng, Lina; Nguyen, Cherwyn M; Patel, Samit; Mlynash, Michael; Caulfield, Anna Finley

2018-03-01

One institution's experience with use of peripheral i.v. (PIV) catheters for prolonged infusions of 3% sodium chloride injection at rates up to 100 mL/hr is described. A prospective, observational, 13-month quality assurance project was conducted at an academic medical center to evaluate frequencies of patient and catheter phlebitis among adult inpatients who received both an infusion of 3% sodium chloride injection for a period of ≥4 hours through a dedicated PIV catheter and infusions of routine-care solutions (RCSs) through separate PIV catheters during the same hospital stay. Sixty patients received PIV infusions through a total of 291 catheters during the study period. The majority of patients (78%) received infusions of 3% sodium chloride injection for intracranial hypertension, with 30% receiving such infusions in the intensive care unit. Phlebitis occurred in 28 patients (47%) during infusions of 3% sodium chloride and 26 patients (43%) during RCS infusions ( p = 0.19). Catheter phlebitis occurred in 73 catheters (25%), with no significant difference in the frequencies of catheter phlebitis with infusion of 3% sodium chloride versus RCSs (30% [32 of 106 catheters]) versus 22% [41 of 185 catheters]), p = 0.16). Patient and catheter phlebitis rates were not significantly different with infusions of 3% sodium chloride injection versus RCSs, suggesting that an osmolarity cutoff value of 900 mOsm/L for peripheral infusions of hypertonic saline solutions may not be warranted. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Fault Detection and Safety in Closed-Loop Artificial Pancreas Systems

PubMed Central

2014-01-01

Continuous subcutaneous insulin infusion pumps and continuous glucose monitors enable individuals with type 1 diabetes to achieve tighter blood glucose control and are critical components in a closed-loop artificial pancreas. Insulin infusion sets can fail and continuous glucose monitor sensor signals can suffer from a variety of anomalies, including signal dropout and pressure-induced sensor attenuations. In addition to hardware-based failures, software and human-induced errors can cause safety-related problems. Techniques for fault detection, safety analyses, and remote monitoring techniques that have been applied in other industries and applications, such as chemical process plants and commercial aircraft, are discussed and placed in the context of a closed-loop artificial pancreas. PMID:25049365

The influence of gastrointestinal infusion of fats on regulation of food intake in pigs.

PubMed Central

Gregory, P C; Rayner, D V

1987-01-01

1. The influence of gastrointestinal infusions of fat on short-term and 24 h control of food intake were studied in twenty-four pigs fed twice per day and seventeen fed three times per day. The pigs were fitted with up to four catheters placed in the stomach, the duodenum, and at 2, 4 and 8 m from the ligament of Treitz. 2. Various infusions were given into the catheters beginning 30 min before the first meal (two feeds) or second meal (three feeds) of the day and continuing until the end of the feeding period or until the pigs stopped eating. 3. Infusions of a fat emulsion (Intralipid) into the stomach, of oleic acid or glycerol into the duodenum, or of glycerol into the ileum (8 m from the ligament of Treitz) inhibited food intake during the infusion according to the amount of energy infused. 4. Food intake was inhibited by more than the amount of energy infused with duodenal infusion of Intralipid or monoglyceride, or with infusion of Intralipid mixed with bile salts and lipase (but not with Intralipid alone) into 2 or 4 m from the ligament of Treitz. 5. Duodenal infusion of glycerol, and ileal (8 m from the ligament of Treitz) infusion of monoglyceride or glycerol inhibited food intake at the following meal according to the amount of energy infused. 6. It is concluded that fats can exert both pre- and post-absorptive control of food intake and that since Intralipid infusion to the stomach but not to the duodenum inhibits food intake according to the amount of energy infused, it is likely that control of food intake is related to control of stomach emptying. 7. The inhibition of food intake by more than the amount of energy infused during upper intestinal infusion of fat is likely to be a result of digestion of the fat to monoglycerides, and interaction of monoglycerides with receptors in the proximal 4 m of intestine. PMID:3656166

The costs of fluid overload in the adult intensive care unit: is a small-volume infusion model a proactive solution?

PubMed Central

Child, Debra L; Cao, Zhun; Seiberlich, Laura E; Brown, Harold; Greenberg, Jordan; Swanson, Anne; Sewall, Martha R; Robinson, Scott B

2015-01-01

Purpose Fluid overload (FO) in critically ill patients remains a challenging clinical dilemma, and many continuous intravenous (IV) medications in the US are being delivered as a dilute solution, adding significantly to a patient’s daily intake. This study describes the costs and outcomes of FO in patients receiving multiple continuous infusions. Materials and methods A retrospective study was conducted using a hospital administrative database covering >500 US hospitals. An FO cohort included adult intensive care unit (ICU) patients with a central line receiving IV loop diuretics and 2+ continuous IV infusions on 50%+ of their ICU days; a directly matched non-FO cohort included patients without IV diuretic use. The primary outcome of the study was total hospitalization costs per visit. Additional outcomes were ICU costs, mortality, total and ICU length of stay (LOS), 30-day readmission rates, and ventilator use. Unadjusted descriptive analysis was performed using chi-squared or paired t-tests to compare outcomes between the two cohorts. Results A total of 63,974 patients were identified in each cohort. The total hospitalization cost per visit for the FO cohort was US$15,344 higher than the non-FO cohort (US$42,386 vs US$27,042), and the ICU cost for the FO cohort was US$5,243 higher than the non-FO cohort (US$10,902 vs US$5,659). FO patients had higher mortality (20% vs 16.8%), prolonged LOS (11.5 vs 8.0 days), longer ICU LOS (6.2 vs 3.6 days), higher risk of 30-day readmission (21.8% vs 21.3%), and ventilator usage (47.7% vs 28.3%) than the non-FO cohort (all P<0.05). Conclusion In patients receiving multiple continuous infusions, FO is associated with increased health care resources and costs. Maximally concentrating medications and proactively providing continuous medications in small-volume infusions (SVI) could be a potential solution to prevent iatrogenic FO in critically ill patients. Further prospective research is warranted to assess the impact of the SVI dispensing model on patient outcomes and health care costs. PMID:25548524

Effect of Continuous Propofol Infusion in Rat on Tau Phosphorylation with or without Temperature Control.

PubMed

Huang, Chunxia; Ng, Olivia Tsz-Wa; Ho, Yuen-Shan; Irwin, Michael Garnet; Chang, Raymond Chuen-Chung; Wong, Gordon Tin-Chun

2016-01-01

Several studies suggest a relationship between anesthesia-induced tau hyperphosphorylation and the development of postoperative cognitive dysfunction. This study further characterized the effects of continuous propofol infusion on tau protein phosphorylation in rats, with or without temperature control. Propofol was administered intravenously to 8-10-week-old male Sprague-Dawley rats and infused to the loss of the righting reflex for 2 h continuously. Proteins from cortex and hippocampus were examined by western blot and immunohistochemistry. Rectal temperature was significantly decreased during propofol infusion. Propofol with hypothermia significantly increased phosphorylation of tau at AT8, AT180, Thr205, and Ser199 in cortex and hippocampus except Ser396. With temperature maintenance, propofol still induced significant elevation of AT8, Thr205, and Ser199 in cortex and hippocampus; however, increase of AT180 and Ser396 was only found in hippocampus and cortex, respectively. Differential effects of propofol with or without hypothermia on multiple tau related kinases, such as Akt/GSK3β, MAPK pathways, or phosphatase (PP2A), were demonstrated in region-specific manner. These findings indicated that propofol increased tau phosphorylation under both normothermic and hypothermic conditions, and temperature control could partially attenuate the hyperphosphorylation of tau. Further studies are warranted to determine the long-term impact of propofol on the tau pathology and cognitive functions.

An assessment of the variation in the concentration of acetylcysteine in infusions for the treatment of paracetamol overdose.

PubMed

Bailey, George P; Wood, David M; Archer, John R H; Rab, Edmund; Flanagan, Robert J; Dargan, Paul I

2017-02-01

Intravenous acetylcysteine is the treatment of choice for paracetamol poisoning. A previous UK study in 2001 found that 39% of measured acetylcysteine infusion concentrations differed by >20% from anticipated concentrations. In 2012, the UK Commission on Human Medicines made recommendations for the management of paracetamol overdose, including provision of weight-based acetylcysteine dosing tables. The aim of this study was to assess variation in acetylcysteine concentrations in administered infusions following the introduction of this guidance. A 6-month single-centre prospective study was undertaken at a UK teaching hospital. After preparation, 5-ml samples were taken from the first, second and third/any subsequent acetylcysteine infusions. Acetylcysteine was measured in diluted (1:50) samples by high-performance liquid chromatography. Comparisons between measured and expected concentrations based on prescribed weight-based dose and volume were made for each infusion. Ninety samples were collected. There was a variation of ≤10% in measured compared to expected concentration for 45 (50%) infusions, of 10-20% for 27 (30%) infusions, 20.1-50% for 14 (16%) infusions and >50% for four (4%) infusions. There was a median (interquartile range) variation in measured compared to expected concentration of -3.6 mg ml -1 (-6.7 to -2.3) for the first infusion, +0.2 mg ml -1 (-0.9 to +0.4) for the second infusion and -0.3 mg ml -1 (-0.6 to +0.2) for third and fourth infusions. There has been a moderate improvement in the variation in acetylcysteine dose administered by infusion. Further work is required to understand the continuing variation and consideration should be given to simplification of acetylcysteine regimes to decrease the risk of administration errors. © 2016 The British Pharmacological Society.

Comparison of clinical efficacy among remifentanil, nicardipine, and remifentanil plus nicardipine continuous infusion for hypotensive anesthesia during arthroscopic shoulder surgery.

PubMed

Kim, Joon Yub; Song, Seong Hun; Cho, Jae Ho; Cho, Hyung Rae

2017-01-01

Hypotensive anesthesia is crucial during arthroscopic shoulder surgery to reduce bleeding and allow for clear visibility. The aim of this study was to compare the clinical efficacy of continuous infusion of remifentanil, nicardipine, and remifentanil plus nicardipine to control hypotensive anesthesia in arthroscopic shoulder surgery. For this study, we enrolled 45 consecutive patients who were scheduled to have arthroscopic rotator cuff repair surgery and randomly allocated them into remifentanil (group R, n = 15), nicardipine (group N, n = 15), and remifentanil plus nicardipine (group RN, n = 15) groups. During the surgeries, these drugs were administered with continuous infusion. We analyzed the mean arterial pressure (MAP) and heart rate during surgery, stay time in the recovery room, visual analogue scale (VAS) scores, use of antiemetics in the recovery room, and postoperative blood urea nitrogen and creatinine changes. The VAS score in the recovery room was higher for group R (mean 5.6, SD 1.4) than for groups N (mean 3.9, SD 0.9) and RN (mean 4.0, SD 1.1; p = 0.000). There were no statistical differences regarding other clinical variables among the three groups (all p > 0.05) except for MAP at 120 min of surgery between groups N and RN (N: 84.67 (SD 10.7) mmHg, RN: 65.4 (SD 9.2) mmHg, p = 0.027). The continuous infusion of remifentanil plus nicardipine appeared to be advantageous for maintaining hypotensive anesthesia until 120 min of arthroscopic shoulder surgery without rebound pain in a postanesthesia care unit.

Effect of tubing on loss of clonazepam administered by continuous subcutaneous infusion.

PubMed

Schneider, Jennifer J; Good, Phillip; Ravenscroft, Peter J

2006-06-01

Previous studies have reported loss of clonazepam from solutions administered intravenously from plastic infusion bags and administration sets. In palliative care, clonazepam is sometimes administered through syringe drivers using polyvinyl chloride (PVC) infusion tubing. No data currently exist to show whether use of PVC tubing affects the amount of clonazepam actually received by the patient. This study compared the use of two different types of PVC tubing with a non-PVC tubing. Solutions containing clonazepam or clonazepam and morphine were prepared with either normal saline or water for injection as diluent. Concentrations of morphine and clonazepam were determined using high-performance liquid chromatography. Significant loss of clonazepam (up to 50%) was observed in all solutions infused through PVC tubing. Solutions infused through non-PVC tubing retained greater than 90% of the initial concentration of clonazepam. It is recommended that when administering clonazepam using a syringe driver, non-PVC tubing be used.

Does des-acyl ghrelin improve glycemic control in obese diabetic subjects by decreasing acylated ghrelin levels?

PubMed

Özcan, Behiye; Neggers, Sebastian J C M M; Miller, Anne Reifel; Yang, Hsiu-Chiung; Lucaites, Virginia; Abribat, Thierry; Allas, Soraya; Huisman, Martin; Visser, Jenny A; Themmen, Axel P N; Sijbrands, Eric J G; Delhanty, Patric J D; van der Lely, Aart Jan

2014-06-01

The objective of this study was to assess the effects of a continuous overnight infusion of des-acyl ghrelin (DAG) on acylated ghrelin (AG) levels and glucose and insulin responses to a standard breakfast meal (SBM) in eight overweight patients with type 2 diabetes. Furthermore, in the same patients and two additional subjects, the effects of DAG infusion on AG concentrations and insulin sensitivity during a hyperinsulinemic-euglycemic clamp (HEC) were assessed. A double-blind, placebo-controlled cross-over study design was implemented, using overnight continuous infusions of 3 and 10  μg DAG/kg per h and placebo to study the effects on a SBM. During a HEC, we studied the insulin sensitivity. We observed that, compared with placebo, overnight DAG administration significantly decreased postprandial glucose levels, both during continuous glucose monitoring and at peak serum glucose levels. The degree of improvement in glycemia was correlated with baseline plasma AG concentrations. Concurrently, DAG infusion significantly decreased fasting and postprandial AG levels. During the HEC, 2.5  h of DAG infusion markedly decreased AG levels, and the M-index, a measure of insulin sensitivity, was significantly improved in the six subjects in whom we were able to attain steady-state euglycemia. DAG administration was not accompanied by many side effects when compared with placebo. DAG administration improves glycemic control in obese subjects with type 2 diabetes through the suppression of AG levels. DAG is a good candidate for the development of compounds in the treatment of metabolic disorders or other conditions with a disturbed AG:DAG ratio, such as type 2 diabetes mellitus or Prader-Willi syndrome. © 2014 European Society of Endocrinology.

Variable use of amiodarone is associated with a greater risk of recurrence of atrial fibrillation in the critically ill.

PubMed

Mitrić, Goran; Udy, Andrew; Bandeshe, Hiran; Clement, Pierre; Boots, Rob

2016-04-02

Atrial fibrillation is a common rhythm disturbance in the general medical-surgical intensive care unit. Amiodarone is a popular drug in this setting but evidence to inform clinical practice remains scarce. We aimed to identify whether variation in the clinical use of amiodarone was associated with recurrent atrial fibrillation. This was a retrospective audit of 177 critically ill patients who developed new-onset atrial fibrillation after admission to a tertiary level medical-surgical trauma intensive care unit. Patterns of amiodarone prescription (including dosage schedule and duration) were assessed in relation to recurrence of atrial fibrillation during the intensive care unit stay. Known recurrence risk factors, such as inotrope administration, cardiac disease indices, Charlson Comorbidity Index, magnesium concentrations, fluid balance, and potassium concentrations, were also included in adjusted analysis using forward stepwise logistic regression modelling. The cohort had a median (interquartile range) age of 69 years (60-75), Acute Physiology and Chronic Health Evalution II score of 22 (17-28) and Charlson Comorbidity Index of 2 (1-4). A bolus dose of amiodarone followed by infusion (P = 0.02), in addition to continuing amiodarone infusion through to discharge from the intensive care unit (P < 0.001), were associated with less recurrent dysrhythmia. Recurrence after successful treatment was associated with ceasing amiodarone while an inotrope infusion continued (P < 0.001), and was more common in patients with a prior history of congestive cardiac failure (P = 0.04), and a diagnosis of systemic inflammatory response syndrome (P = 0.02). Amiodarone should be administered as a bolus dose followed immediately with an infusion when treating atrial fibrillation in the medical-surgical intensive care unit. Consideration should be given to continuing amiodarone infusions in patients on inotropes until they are ceased.

Aggressive Treatment of Life-Threatening Hypophosphatemia During Recovery From Fulminant Hepatic Failure: A Case Report.

PubMed

Bissell, Brittany D; Davis, Jason E; Flannery, Alexander H; Adkins, David A; Thompson Bastin, Melissa L

2018-06-01

Acute liver failure secondary to acetaminophen overdose can be a life-threatening condition, characterized by severe electrolyte derangements. Hepatocyte regeneration is associated with phosphorous utilization and is a known complication of liver recovery following injury. We report the case of profound, life-threatening hypophosphatemia following recovery from acute fulminant liver failure. As the liver enzymes normalized, serum phosphorous levels plummeted. Our patient required an aggressive, individualized phosphorus replacement regimen, which resulted in a continuous infusion of intravenous (IV) sodium phosphate, titrated to a maximum rate of 30 mmol/h or 0.5 mmol/kg/h. The patient required over 400 mmol of total IV and oral phosphorous over the course of 48 hours. An aggressive approach to phosphorous replacement was done safely and effectively. Traditional replacement protocols are not adequate to sustain patients with this degree of hypophosphatemia. This is the first report to utilize a continuous infusion of phosphate with a maximum reported rate (0.5 mmol/kg/h). Our report summarizes a novel and safe approach for clinicians to maximally support these patients through high-dose, continuous infusion phosphorous administration.

Continuous thermographic observation may predict extravasation in chemotherapy-treated patients.

PubMed

Oya, Maiko; Murayama, Ryoko; Oe, Makoto; Yabunaka, Koichi; Tanabe, Hidenori; Takahashi, Toshiaki; Matsui, Yuko; Otomo, Eiko; Komiyama, Chieko; Sanada, Hiromi

2017-06-01

Extravasation, or leakage of vesicant drugs into subcutaneous tissues, causes serious complications such as induration and necrosis in chemotherapy-treated patients. As macroscopic observation may overlook symptoms during infusion, we focused on skin temperature changes at puncture sites and studied thermographic patterns related to induration or necrosis caused by extravasation. Outpatients undergoing chemotherapy using peripheral intravenous catheters were enrolled in this prospective observational study. We filmed and classified infrared thermography movies of puncture sites during infusion; ultrasonography was also utilized at puncture sites to observe the subcutaneous condition. Multiple logistic regression analysis was performed to examine the association of thermographic patterns with induration or necrosis observed on the next chemotherapy day. Differences in patient characteristics, puncture sites, and infusions were analyzed by Mann-Whitney's U test and Fisher's exact test according to thermographic patterns. Eight patients developed induration among 74 observations in 62 patients. Among six thermographic patterns, a fan-shaped lower temperature area gradually spreading from the puncture site (fan at puncture site) was significantly associated with induration. Ultrasonography revealed that catheters of patients with fan at puncture site remained in the vein at the end of infusion, indicating that the infusion probably leaked from the puncture site. Patients with fan at puncture site had no significant differences in characteristics and infusion conditions compared with those with the other five thermographic patterns. We determined that fan at puncture site was related to induration caused by extravasation. Continuous thermographic observation may enable us to predict adverse events of chemotherapy. Copyright © 2017. Published by Elsevier Ltd.

Pathology in Continuous Infusion Studies in Rodents and Non-Rodents and ITO (Infusion Technology Organisation)-Recommended Protocol for Tissue Sampling and Terminology for Procedure-Related Lesions

PubMed Central

Weber, Klaus; Mowat, Vasanthi; Hartmann, Elke; Razinger, Tanja; Chevalier, Hans-Jörg; Blumbach, Kai; Green, Owen P.; Kaiser, Stefan; Corney, Stephen; Jackson, Ailsa; Casadesus, Agustin

2011-01-01

Many variables may affect the outcome of continuous infusion studies. The results largely depend on the experience of the laboratory performing these studies, the technical equipment used, the choice of blood vessels and hence the surgical technique as well the quality of pathological evaluation. The latter is of major interest due to the fact that the pathologist is not involved until necropsy in most cases, i.e. not dealing with the complicated surgical or in-life procedures of this study type. The technique of tissue sampling during necropsy and the histology processing procedures may influence the tissues presented for evaluation, hence the pathologist may be a source of misinterpretation. Therefore, ITO proposes a tissue sampling procedure and a standard nomenclature for pathological lesions for all sites and tissues in contact with the port-access and/or catheter system. PMID:22272050

[Continuous subcutaneous infusion in palliative care, an undervalued method].

PubMed

van Marum, R J; de Vogel, E M; Zylicz, Z

2002-11-23

Three patients, 2 men aged 55 and 54 years and a woman aged 86 years, were admitted to hospital for treatment of symptoms resulting from terminal disease (pain, agitation, nausea etc.). In all three patients, continuous subcutaneous infusion (CSI) of medication was successfully used to control the symptoms. Compared with intravenous infusion, the technique of CSI is easy to learn and is associated with fewer complications. Its reliability and ease-of-use make it a technique that can be used not only in a hospital setting, but also in general practice and nursing homes. Medication used in palliative care (e.g. morphine, haloperidol, metoclopramide, levomepromazine, midazolam) can often be administered safely by CSI. In palliative care, where goals should be accomplished with minimal burden to the patient, CSI must be considered the technique of choice in patients who are unable to swallow their medication.

Evaluating the Efficacy of Nocturnal Continuous Subcutaneous Apomorphine Infusion in Sleep Disorders in Advanced Parkinson's Disease: The APO-NIGHT Study.

PubMed

Fernández-Pajarín, Gustavo; Sesar, Ángel; Ares, Begoña; Castro, Alfonso

2016-10-19

There are not many data about the beneficial effect of nocturnal continuous subcutaneous apomorphine infusion (NCSAI) over sleep disturbances in advanced Parkinson's disease (PD). Evaluate the effect of the NCSAI in sleeping problems and insomnia due to nocturnal hypokinesia inadvanced PD. We assessed 17 advanced PD patients with several sleep disturbances measured by SCOPA-SLEEP and PDSS scales. All the patients were on apomorphine infusion during daytime. This therapy was extended to nighttime. We evaluated the patients before the onset and after six weeks with NCSAI. NCSAI allowed highly significant improvements in SCOPA-SLEEP and PDSS scales (p<0.0001), and daytime somnolence. NCSAI was well tolerated with no major adverse effects were noticed. This study shows and confirms the efficacy of NCSAI on the sleep disturbances related to advanced PD. We provide an easy protocol to start this therapy.

Modeling the non-steady state respiratory effects of remifentanil in awake and propofol-sedated healthy volunteers.

PubMed

Olofsen, Erik; Boom, Merel; Nieuwenhuijs, Diederik; Sarton, Elise; Teppema, Luc; Aarts, Leon; Dahan, Albert

2010-06-01

Few studies address the dynamic effect of opioids on respiration. Models with intact feedback control of carbon dioxide on ventilation (non-steady-state models) that correctly incorporate the complex interaction among drug concentration, end-tidal partial pressure of carbon dioxide concentration, and ventilation yield reliable descriptions and predictions of the behavior of opioids. The authors measured the effect of remifentanil on respiration and developed a model of remifentanil-induced respiratory depression. Ten male healthy volunteers received remifentanil infusions with different infusion speeds (target concentrations: 4-9 ng/ml; at infusion rates: 0.17-9 ng x ml x min) while awake and at the background of low-dose propofol. The data were analyzed with a nonlinear model consisting of two additive linear parts, one describing the depressant effect of remifentanil and the other describing the stimulatory effect of carbon dioxide on ventilation. The model adequately described the data including the occurrence of apnea. Most important model parameters were as follows: C50 for respiratory depression 1.6 +/- 0.03 ng/ml, gain of the respiratory controller (G) 0.42 - 0.1 l x min x Torr, and remifentanil blood effect site equilibration half-life (t(1/2)ke0) 0.53 +/- 0.2 min. Propofol caused a 20-50% reduction of C50 and G but had no effect on t(1/2)ke0. Apnea occurred during propofol infusion only. A simulation study revealed an increase in apnea duration at infusion speeds of 2.5-0.5 ng x ml x min followed by a reduction. At an infusion speed of < or = 0.31 ng x ml x min, no apnea was seen. The effect of varying remifentanil infusions with and without a background of low-dose propofol on ventilation and end-tidal partial pressure of carbon dioxide concentration was described successfully using a non-steady-state model of the ventilatory control system. The model allows meaningful simulations and predictions.

An infiltration/cure model for manufacture of fabric composites by the resin infusion process

NASA Technical Reports Server (NTRS)

Weideman, Mark H.; Loos, Alfred C.; Dexter, H. Benson; Hasko, Gregory H.

1992-01-01

A 1-D infiltration/cure model was developed to simulate fabrication of advanced textile composites by the resin film infusion process. The simulation model relates the applied temperature and pressure processing cycles, along with the experimentally measured compaction and permeability characteristics of the fabric preforms, to the temperature distribution, the resin degree of cure and viscosity, and the infiltration flow front position as a function of time. The model also predicts the final panel thickness, fiber volume fraction, and resin mass for full saturation as a function of compaction pressure. Composite panels were fabricated using the RTM (Resin Transfer Molding) film infusion technique from knitted, knitted/stitched, and 2-D woven carbon preforms and Hercules 3501-6 resin. Fabric composites were fabricated at different compaction pressures and temperature cycles to determine the effects of the processing on the properties. The composites were C-scanned and micrographed to determine the quality of each panel. Advanced cure cycles, developed from the RTM simulation model, were used to reduce the total cure cycle times by a factor of 3 and the total infiltration times by a factor of 2.

Low-Dose Ketamine Infusion for Emergency Department Patients with Severe Pain.

PubMed

Ahern, Terence L; Herring, Andrew A; Miller, Steve; Frazee, Bradley W

2015-07-01

Use of low-dose ketamine infusions in the emergency department (ED) has not previously been described, despite routine use in perioperative and other settings. Our hypothesis was that a low-dose ketamine bolus followed by continuous infusion would 1) provide clinically significant and sustained pain relief; 2) be well tolerated; and 3) be feasible in the ED. We prospectively administered 15 mg intravenous ketamine followed immediately by continuous ketamine infusion at 20 mg/h for 1 hour. Optional morphine (4 mg) was offered at 20, 40, and 60 minutes. Pain intensity, vitals signs, level of sedation, and adverse reactions were assessed for 120 minutes. A total of 38 patients were included with a median initial numerical rating scale (NRS) pain score of 9. At 10 minutes, the median reduction in pain score was 4, with 7 patients reporting a score of 0. At 60 and 120 minutes, 25 and 26 patients, respectively, reported clinically significant pain reduction (decrease NRS score > 3). Heart rate, blood pressure, respiratory rate, and oxygen saturation remained stable. Mild or moderate side effects including dizziness, fatigue, and headache were common. Patient satisfaction was high; 85% reported they would have this medication again for similar pain. A low-dose ketamine infusion protocol provided significant pain relief with mostly mild side effects and no severe adverse events. Wiley Periodicals, Inc.

Digital Model-Based Engineering: Expectations, Prerequisites, and Challenges of Infusion

NASA Technical Reports Server (NTRS)

Hale, J. P.; Zimmerman, P.; Kukkala, G.; Guerrero, J.; Kobryn, P.; Puchek, B.; Bisconti, M.; Baldwin, C.; Mulpuri, M.

2017-01-01

Digital model-based engineering (DMbE) is the use of digital artifacts, digital environments, and digital tools in the performance of engineering functions. DMbE is intended to allow an organization to progress from documentation-based engineering methods to digital methods that may provide greater flexibility, agility, and efficiency. The term 'DMbE' was developed as part of an effort by the Model-Based Systems Engineering (MBSE) Infusion Task team to identify what government organizations might expect in the course of moving to or infusing MBSE into their organizations. The Task team was established by the Interagency Working Group on Engineering Complex Systems, an informal collaboration among government systems engineering organizations. This Technical Memorandum (TM) discusses the work of the MBSE Infusion Task team to date. The Task team identified prerequisites, expectations, initial challenges, and recommendations for areas of study to pursue, as well as examples of efforts already in progress. The team identified the following five expectations associated with DMbE infusion, discussed further in this TM: (1) Informed decision making through increased transparency, and greater insight. (2) Enhanced communication. (3) Increased understanding for greater flexibility/adaptability in design. (4) Increased confidence that the capability will perform as expected. (5) Increased efficiency. The team identified the following seven challenges an organization might encounter when looking to infuse DMbE: (1) Assessing value added to the organization. Not all DMbE practices will be applicable to every situation in every organization, and not all implementations will have positive results. (2) Overcoming organizational and cultural hurdles. (3) Adopting contractual practices and technical data management. (4) Redefining configuration management. The DMbE environment changes the range of configuration information to be managed to include performance and design models, database objects, as well as more traditional book-form objects and formats. (5) Developing information technology (IT) infrastructure. Approaches to implementing critical, enabling IT infrastructure capabilities must be flexible, reconfigurable, and updatable. (6) Ensuring security of the single source of truth (7) Potential overreliance on quantitative data over qualitative data. Executable/ computational models and simulations generally incorporate and generate quantitative vice qualitative data. The Task team also developed several recommendations for government, academia, and industry, as discussed in this TM. The Task team recommends continuing beyond this initial work to further develop the means of implementing DMbE and to look for opportunities to collaborate and share best practices.

The U.S. home infusion market.

PubMed

Monk-Tutor, M R

1998-10-01

Medicare legislation stimulated the development of home care services but also resulted in fragmentation of service components. In the 1980s, prospective pricing and diagnosis-related groups, and resulting pressures to reduce inpatient length of stay, prompted additional growth of the industry. Even so, in 1995 home care represented only 3% of total national expenditures on health care. The annual growth rate of the home infusion industry dropped from 64% in 1982-86 to 24% in 1986-93. While revenue per patient for home infusion is expected to decrease under managed care, an increasing number of patients will support continued market growth. The home infusion market is highly competitive, with only a few large national providers and many small local providers. In 1996, 29% of acute care hospitals provided or were developing a home care program. Community pharmacists' options in the home infusion area include independent services, partnerships, joint ventures, contracts with hospitals, and franchises. The home infusion market is being integrated into alternative sites, such as ambulatory infusion centers (AICs), as providers attempt to diversify to maintain managed care contracts. AICs provide infusion therapy and nursing to noninstitutionalized, nonhome-bound patients. Untapped sources for future growth of the infusion market include long-term-care facilities. More consistent studies of the home care market are needed. Despite slowed growth in recent years, home care has a strong market in the United States.

Regulation of branchial V-H(+)-ATPase, Na(+)/K(+)-ATPase and NHE2 in response to acid and base infusions in the Pacific spiny dogfish (Squalus acanthias).

PubMed

Tresguerres, Martin; Katoh, Fumi; Fenton, Heather; Jasinska, Edyta; Goss, Greg G

2005-01-01

To study the mechanisms of branchial acid-base regulation, Pacific spiny dogfish were infused intravenously for 24 h with either HCl (495+/- 79 micromol kg(-1) h(-1)) or NaHCO(3) (981+/-235 micromol kg(-1) h(-1)). Infusion of HCl produced a transient reduction in blood pH. Despite continued infusion of acid, pH returned to normal by 12 h. Infusion of NaHCO(3) resulted in a new steady-state acid-base status at approximately 0.3 pH units higher than the controls. Immunostained serial sections of gill revealed the presence of separate vacuolar proton ATPase (V-H(+)-ATPase)-rich or sodium-potassium ATPase (Na(+)/K(+)-ATPase)-rich cells in all fish examined. A minority of the cells also labeled positive for both transporters. Gill cell membranes prepared from NaHCO(3)-infused fish showed significant increases in both V-H(+)-ATPase abundance (300+/-81%) and activity. In addition, we found that V-H(+)-ATPase subcellular localization was mainly cytoplasmic in control and HCl-infused fish, while NaHCO(3)-infused fish demonstrated a distinctly basolateral staining pattern. Western analysis in gill membranes from HCl-infused fish also revealed increased abundance of Na(+)/H(+) exchanger 2 (213+/-5%) and Na(+)/K(+)-ATPase (315+/-88%) compared to the control.

Pantoprazole before Endoscopy in Patients with Gastroduodenal Ulcer Bleeding: Does the duration of Infusion and Ulcer Location Influence the Effects?

PubMed Central

Rácz, Istvan; Szalai, Milan; Dancs, Nora; Kárász, Tibor; Szabó, Andrea; Csöndes, Mihaly; Horváth, Zoltan

2012-01-01

The aim of this study was to investigate the effect of preemptive pantoprazole infusion on early endoscopic findings in patients with acute ulcer bleeding. Records of 333 patients admitted with acute ulcer bleeding were analyzed. Ulcer bleeders were given either 80 mg bolus of pantoprazole followed by continuous infusion of 8 mg per hour or saline infusion until endoscopy. In 93 patients saline infusion whereas in 240 patients bolus plus infusion of pantoprazole was administrated with mean (±SD) durations of 5.45 ± 12.9 hours and 6.9 ± 13.2 hours, respectively (P = 0.29). Actively bleeding ulcers were detected in 46/240 (19.2%) of cases in the pantoprazole group as compared with 23/93 (24.7%) in the saline infusion group (P = 0.26). Different durations of pantoprazole infusion (0–4 hours, >4 hours, and >6 hours) had no significant effect on endoscopic and clinical outcome parameters in duodenal ulcer bleeders. Gastric ulcer bleeders on pantoprazole infusion longer than 4 and 6 hours before endoscopy had actively bleeding ulcers in 4.3% and 5% compared to the 19.5% active bleeding rate in the saline group (P = 0.02 and P = 0.04). Preemptive infusion of high-dose pantoprazole longer than 4 hours before endoscopy decreased the ratio of active bleeding only in gastric but not in duodenal ulcer patients. PMID:23125849

Subcutaneous infusion in palliative care: a focus on the neria soft 90 infusion set.

PubMed

Gabriel, Janice

2014-11-01

Subcutaneous administration of medications and/or fluids can play a crucial part in supporting patients at home and thereby avoiding the need for hospitalisation. It is an area of patient care that has received little attention compared with other types of parenteral therapies. However, it is an effective and safe route for continuous administration for individuals requiring palliative care. Technological advancements have led to improved subcutaneous infusion devices, such as fine-gauge cannulae with integral sharps protection, as well as integral hypoallergenic dressings. These design features not only help to increase patient comfort but also minimise the potential for needlestick injuries, as well as providing the health professional with one sterile package containing all of the components needed to establish subcutaneous infusion. However, technological developments alone are insufficient to improve patient outcomes. Knowledge of the individual patient, together with their diagnosis and intended treatment, will influence the choice of subcutaneous infusion device, with the overall aim of minimising the potential for complications and improving comfort. This paper provides an overview of subcutaneous infusion, including the importance of patient assessment and the education and training needs of health professionals, and then focuses on one specific subcutaneous infusion device: the neria soft 90 infusion set.

Evaluation of drug-metabolizing and functional competence of human hepatocytes incubated under hypothermia in different media for clinical infusion.

PubMed

Gómez-Lechón, María José; Lahoz, Agustín; Jiménez, Nuria; Bonora, Ana; Castell, José V; Donato, María Teresa

2008-01-01

Hepatocyte transplantation has been proposed as a method to support patients with liver insufficiency. Key factors for clinical cell transplantation to progress is to prevent hepatocyte damage, loss of viability and cell functionality, factors that depend on the nature of the tissue used for isolation to a large extent. The main sources of tissue for hepatocyte isolation are marginal livers that are unsuitable for transplantation, and segments from reduced cadaveric grafts. Hepatocellular transplantation requires infusing human hepatocytes in suspension over a period of minutes to hours. The beneficial effect of hypothermic preservation of hepatocytes in infusion medium has been reported, but how critical issues towards the success of cell transplantation, such as the composition of infusion medium and duration of hepatocyte storage will affect hepatocyte quality for clinical cell infusion has not been systematically investigated. Infusion media composition is phosphate-buffered saline containing anticoagulants and human serum albumin. The supplementation of infusion media with glucose or N-acetyl-cystein, or with both components at the same time, has been investigated. After isolation, hepatocytes were suspended in each infusion medium and a sample at the 0 time point was harvested for cell viability and functional assessment. Thereafter, cells were incubated in different infusion media agitated on a rocker platform to simulate the clinical infusion technique. The time course of hepatocyte viability, funtionality (drug-metabolizing enzymes, ureogenic capability, ATP, glycogen, and GSH levels), apoptosis (caspase-3 activation), and attachment and monolayer formation were analyzed. The optimal preservation of cell viability, attaching capacity, and functionality, particularly GSH and glycogen levels, as well as drug-metabolizing cytochrome P450 enzymes, was found in infusion media supplemented with 2 mM N-acetyl-cystein and 15 mM glucose.

[Consensus document on continuous subcutaneous insulin infusion (CSII) treatment in paediatrics with type I diabetes].

PubMed

Barrio Castellanos, R; García Cuartero, B; Gómez Gila, A; González Casado, I; Hermoso López, F; Luzuriaga Tomás, C; Oyarzabal Irigoyen, M; Rica Etxebarria, I; Rodríguez Rigual, M; Torres Lacruz, M

2010-05-01

This article reports on the Spanish Position Statement for the Diabetes Pediátric Group for the Spanish Pediatric Endocrinology Society (SEEP) on continuous subcutaneous insulin infusion in children and adolescents with type 1 diabetes. The practical issues about their indications, appropriate candidates, feasibility, and limits are outlined. The conclusions are based on the comprehensive review and balanced assessment of the evidence base on the international consensus and consensual answers to these questions for the participants. Copyright 2009 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Subcutaneous glucagon infusion and continuous glucose monitoring enable effective management of hypoglycemia in a patient with IGF-2-producing hemangiopericytoma.

PubMed

Buras, Eric D; Weatherup, Emily; Wyckoff, Jennifer

2018-01-01

Ectopic insulin-like growth factor (IGF)-2 production is a rare complication of an array of epithelial and mesenchymal tumors, and can clinically manifest as life-threatening hypoglycemia. A 49-year-old woman with 13-year history of metastatic hemangiopericytoma, previously treated with multiple rounds of chemotherapy and palliative radiation, presented to the emergency department after a hypoglycemic seizure. On arrival, glucose was 18 mg/dL (1.0 mmol/L) and required continuous dextrose infusion for maintenance within normal limits. Insulin was <2.0 μU/mL, C-peptide 0.1 ng/mL, and beta-hydroxybutyrate <0.2 mmol/L. Random cortisol was 21 μg/dL; sulfonylurea screen, and insulin antibodies were negative. IGF-2 level was 1320 ng/mL; IGF-1 was within normal limits and IGF binding protein (BP)-3 suppressed. Dexamethasone, started at 6 mg twice daily, allowed discontinuation of the glucose infusion. Given concern for nocturnal hypoglycemia, and patient interest in steroid-sparing anti-hypoglycemic regimen, she was also started on overnight continuous subcutaneous glucagon infusion via insulin pump. She was discharged with instructions to maintain a diet high in complex carbohydrates during the day, while utilizing glucagon pump at night. She was also started on continuous glucose monitoring system (CGMS) with an alarm to warn of hypoglycemia. Glucagon infusion rate was later titrated based on CGMS readings. Abdominal CT revealed increasing size of a right upper quadrant mass not previously subjected to radiotherapy. After radiation to this area, hypoglycemia improved, allowing further glucagon titration. In parallel, IGF-2 level declined to 380 ng/mL. Ectopic IGF-2 production is a rare but often fatal complication of many cancers, and should be considered on the differential diagnosis in patients with malignancy and unexplained hypoglycemia. Once hypoglycemia is diagnosed, patients often have end-stage disease. While treatment of the causative tumor is the only definitive intervention, anti-hypoglycemia therapy is a life-saving, temporizing measure. In this case, the patient attained euglycemia and survived 3 months after presentation before ultimately succumbing to other malignancy-related complications. Given efficacy in management of hypoglycemia while awaiting definitive tumor-directed therapy, we submit nighttime subcutaneous glucagon infusion and CGMS are valuable additions to the physician's armamentarium in managing this condition.

Circadian rhythm of energy expenditure and oxygen consumption.

PubMed

Leuck, Marlene; Levandovski, Rosa; Harb, Ana; Quiles, Caroline; Hidalgo, Maria Paz

2014-02-01

This study aimed to evaluate the effect of continuous and intermittent methods of enteral nutrition (EN) administration on circadian rhythm. Thirty-four individuals, aged between 52 and 80 years, were fed through a nasoenteric tube. Fifteen individuals received a continuous infusion for 24 hours/d, and 19 received an intermittent infusion in comparable quantities, every 4 hours from 8:00 to 20:00. In each patient, 4 indirect calorimetric measurements were carried out over 24 hours (A: 7:30, B: 10:30, C: 14:30, and D: 21:30) for 3 days. Energy expenditure and oxygen consumption were significantly higher in the intermittent group than in the continuous group (1782 ± 862 vs 1478 ± 817 kcal/24 hours, P = .05; 257 125 vs 212 117 ml/min, P = .048, respectively). The intermittent group had higher levels of energy expenditure and oxygen consumption at all the measured time points compared with the continuous group. energy expenditure and oxygen consumption in both groups were significantly different throughout the day for 3 days. There is circadian rhythm variation of energy expenditure and oxygen consumption with continuous and intermittent infusion for EN. This suggests that only one indirect daily calorimetric measurement is not able to show the patient's true needs. Energy expenditure is higher at night with both food administration methods. Moreover, energy expenditure and oxygen consumption are higher with the intermittent administration method at all times.

Development and Implementation of a Curriculum Infusion Plan for Alcohol Abuse Education in a College Population

ERIC Educational Resources Information Center

Kenney, Sarah; Grim, Melissa

2015-01-01

Background: College binge drinking continues to be a pervasive issue across campuses nationwide. Though curriculum infusion (CI) has been shown to be an effective strategy to reduce students' negative consequences related to alcohol, information about the process is limited. Purpose: The purpose of this study is to examine the content and process…

What Happens when the Research Ends? Factors Related to the Sustainability of a Technology-Infused Mathematics Curriculum

ERIC Educational Resources Information Center

Fishman, Barry; Penuel, William R.; Hegedus, Stephen; Roschelle, Jeremy

2011-01-01

This study examines factors related to the sustainability of SimCalc Mathworlds (SCMW), a technology-infused mathematics curriculum. We surveyed middle school teachers one year after their participation in a randomized trial where they were introduced to SCMW curriculum, to identify factors related to their continued use of the materials in ways…

Treatment of Parkinson's disease could be regulated by movement sensors: subcutaneous infusion of varying apomorphine doses according to the intensity of motor activity.

PubMed

Rodríguez-Molinero, Alejandro; Pérez-Martínez, David A; Català, Andreu; Cabestany, Joan; Yuste, Antonio

2009-04-01

Most recent therapeutic solutions to treat Parkinson's disease seek continuous administration of dopaminergic agonists, as for example rigotine patches or apomorphine infusion pumps. Such drug-delivery devices are aimed at preventing fluctuations in drug plasma levels, which could cause certain symptoms such as wearing-off periods or dyskinesia. However, we postulate that drug plasma levels should not keep constant, but rather adjust to the varying intensity of the different user's activities. The rationale behind this is that the drug amount appropriate to treat a patient at rest is lower than that required to treat the same patient when engaged in physical activity. We propose dynamic real-time dose adjustment, so that the doses increase as the patient starts performing physical activity, thus preventing off periods such as "freeze" phenomenon, and the doses reduce during the resting periods, thus preventing adverse effects. Small portable movement sensors are currently available, which detect the amount and type of activity in a continuous way. Combining such technology with infusion pumps to produce modified pumps capable of adjusting the infusion rate to the user's activity, seems to be feasible in the short-term.

Drug withdrawal symptoms in children after continuous infusions of fentanyl.

PubMed

French, J P; Nocera, M

1994-04-01

The purpose of this research was to determine the extent to which critically ill infants exhibited signs and symptoms of narcotic withdrawal after receiving continuous infusions of fentanyl. The convenience sample consisted of 12 pediatric intensive care unit (PICU) patients under 25 months of age who received fentanyl infusions for at least 24 hours. Drug withdrawal symptoms were monitored using the Neonatal Abstinence Score Tool (NAST), which assigns a score to each behavior indicative of withdrawal. A score of 8 or greater indicates Neonatal Abstinence Syndrome (NAS). Scoring began 4 hours after discontinuation of fentanyl and was conducted once per hour for 8 hours. Six subjects had a NAST score exceeding 8; these infants frequently exhibited tremors with or without stimulation, increased muscle tone, insomnia, and increased respiratory rate and effort. There were significant correlations between fentanyl dosage and NAST score (r = .76, p < 0.01), between length of infusion of fentanyl and NAST score (r = .70, p < 0.05), and between chloral hydrate dosage and NAST score (r = .62, p < 0.05). These findings suggest the need for an observation protocol and a possible weaning regimen after fentanyl is discontinued.

Sonothrombolysis of Intra-Catheter Aged Venous Thrombi Using Microbubble Enhancement and Guided Three Dimensional Ultrasound Pulses

PubMed Central

Kutty, Shelby; Xie, Feng; Gao, Shunji; Drvol, Lucas K; Lof, John; Fletcher, Scott E; Radio, Stanley J; Danford, David A; Hammel, James M; Porter, Thomas R

2010-01-01

Central venous and arterial catheters are a major source of thrombo-embolic disease in children. We hypothesized that guided high mechanical index (MI) impulses from diagnostic three-dimensional (3D) ultrasound during an intravenous microbubble infusion could dissolve these thrombi. An in vitro system simulating intra-catheter thrombi was created and then treated with guided high MI impulses from 3D ultrasound, utilizing low MI microbubble sensitive imaging pulse sequence schemes to detect the microbubbles (Perflutren Lipid Microsphere, Definity®, Lantheus). Ten aged thrombi over 24 hours old were tested using 3D ultrasound coupled with a continuous diluted microbubble infusion (Group A), and ten with 3D ultrasound alone (Group B). Mean thrombus age was 28.6 hours (range 26.6–30.3). Groups A exhibited a 55 ± 19 % reduction in venous thrombus size, compared to 31±10 % for Group B (p=0.008). Feasibility testing was performed in 4 pigs, establishing a model to further investigate the efficacy. Sonothrombolysis of aged intra-catheter venous thrombi can be achieved with commercially available microbubbles and guided high MI ultrasound from a diagnostic 3D transducer. PMID:20696549

Subcutaneous drug infusions: a review of problems and solutions.

PubMed

Mitten, T

2001-02-01

Subcutaneous drug infusion using a portable syringe driver has had a significant impact on patient comfort in palliative care. It permits the continuous delivery of a range of drug therapies, so bypassing problems of dysphagia, weakness and the inability of many patients in the terminal phase to take oral medication. The devices are not problem-free, however. Mechanical problems, reactions at the infusion site and difficulties with the mixing of drugs in the syringe are all widely recognized. This article reviews some general issues with the operation of portable syringe drivers, and discusses a range of potential problems and their solutions.

Role of rumen butyrate in regulation of nitrogen utilization and urea nitrogen kinetics in growing sheep.

PubMed

Agarwal, U; Hu, Q; Baldwin, R L; Bequette, B J

2015-05-01

Butyrate, a major rumen VFA, has been indirectly linked to enhancement of urea recycling on the basis of increased expression of urea transporter in the rumen epithelia of steers fed a rumen butyrate-enhancing diet. Two studies were conducted to quantify the effect of elevated rumen butyrate concentrations on N balance, urea kinetics and rumen epithelial proliferation. Wether sheep (n= 4), fitted with a rumen cannula, were fed a pelleted ration (∼165 g CP/kg DM, 10.3 MJ ME/kg DM) at 1.8 × ME requirement. In Exp. 1, sheep were infused intraruminally with either an electrolyte buffer solution (Con-Buf) or butyrate dissolved in the buffer solution (But-Buf) during 8-d periods in a balanced crossover design. In Exp. 2, sheep were infused intraruminally with either sodium acetate (Na-Ac) or sodium butyrate (Na-But) for 9 d. All solutions were adjusted to pH 6.8 and 8.0 in Exp. 1 and 2, respectively, and VFA were infused at 10% of ME intake. [15N2] urea was continuously infused intravenously for the last 5 d of each period, and total urine and feces were collected. In Exp. 1, 2H5-phenylalanine was continuously infused intravenously over the last 12 h, after which a biopsy from the rumen papillae was taken for measurement of fractional protein synthesis rate (FSR). Butyrate infusion treatments increased (P = 0.1 in Exp. 1; P < 0.05 in Exp. 2) the proportion of rumen butyrate, and acetate infusion increased (P < 0.05) rumen acetate. All animals were in positive N balance (4.2 g N/d in Exp. 1; 7.0 g N/d in Exp. 2), but no difference in N retention was observed between treatments. In Exp. 2, urea entry (synthesis) rate was reduced ( < 0.05) by Na-But compared with the Na-Ac control. In Exp. 1, although But-Buf infusion increased the FSR of rumen papillae (35.3% ± 1.08%/d vs. 28.7% ± 1.08%/d; P < 0.05), urea kinetics were not altered by But-Buf compared with Con-Buf. These studies are the first to directly assess the role of butyrate in urea recycling and its effects on rumen papillae protein turnover in growing lambs. Under the feeding conditions used and the rate of continuous butyrate infusion into the rumen in the present studies, butyrate does not affect overall N retention in growing sheep. However, butyrate may play a role in the redistribution of urea N fluxes in the overall scheme of N metabolism.

A real-world, multi-site, observational study of infusion time and treatment satisfaction with rheumatoid arthritis patients treated with intravenous golimumab or infliximab.

PubMed

Daniel, Shoshana R; McDermott, John D; Le, Cathy; Pierce, Christine A; Ziskind, Michael A; Ellis, Lorie A

2018-05-25

To assess real-world infusion times for golimumab (GLM-IV) and infliximab (IFX) for rheumatoid arthritis (RA) patients and factors associated with treatment satisfaction. An observational study assessed infusion time including: clinic visit duration, RA medication preparation and infusion time, and infusion process time. Satisfaction was assessed by a modified Treatment Satisfaction Questionnaire for Medication (patient) and study-specific questionnaires (patient and clinic personnel). Comparative statistical testing for patient data utilized analysis of variance for continuous measures, and Fisher's exact or Chi-square test for categorical measures. Multivariate analysis was performed for the primary time endpoints and patient satisfaction. One hundred and fifty patients were enrolled from six US sites (72 GLM-IV, 78 IFX). The majority of patients were female (80.0%) and Caucasian (88.7%). GLM-IV required fewer vials per infusion (3.7) compared to IFX (4.9; p = .0001). Clinic visit duration (minutes) was shorter for GLM-IV (65.1) compared to IFX (153.1; p < .0001), as was total infusion time for RA medication (32.8 GLM-IV, 119.5 IFX; p < .0001) and infusion process times (45.8 GLM-IV, 134.1 IFX; p < .0001). Patients treated with GLM-IV reported higher satisfaction ratings with infusion time (p < .0001) and total visit time (p = .0003). Clinic personnel reported higher satisfaction with GLM-IV than IFX specific to medication preparation time, ease of mixing RA medication, frequency of patients requiring pre-medication, and infusion time. Findings may not be representative of care delivery for all RA infusion practices or RA patients. Shorter overall clinic visit duration, infusion process, and RA medication infusion times were observed for GLM-IV compared to IFX. A shorter duration in infusion time was associated with higher patient and clinic personnel satisfaction ratings.

Mathematical and physical model of gravity-fed infusion outflow: application to soft-bag-packed solutions.

PubMed

Simon, N; Décaudin, B; Lannoy, D; Barthélémy, C; Lemdani, M; Odou, P

2011-12-01

Gravity-fed infusion (GFI) systems are acknowledged as being unable to keep their flow-rate constant. This may affect drug plasma levels such as aminoglycosides. Numerous factors have previously been cited, but their relative importance has never been quantified so far. The objective of this work is to identify the main factors that influence GFI in vitro outflow and to propose a mathematical model of flow-rate evolution as a function of time. In this model, pressure loss and infusion device creep have been considered as the main variation factors. Concomitantly, two experiments were undertaken. Firstly, the flow-rate evolution of an in vitro infusion of 250 mL of dextrose 5% was assessed. Secondly, the creep occurring on an infusion device was measured through a stress relaxation experiment. The experimental infusion flow-rate decreased by as much as 28.5% over 1 h. Simulated and experimental data are well correlated (r = 0.987; P < 0.0001). The maximum creep effect happens during the first 15 min of infusion. In this work, height of the liquid in the bag and tube creep were found to be the main variation factors in GFI flow-rate. This new mathematical model should help to explain the differences observed in drug plasma levels with gravity-fed devices.

Workplace Simulation: An Integrated Approach to Training University Students in Professional Communication

ERIC Educational Resources Information Center

Ismail, Norhayati; Sabapathy, Chitra

2016-01-01

In the redesign of a professional communication course for real estate students, a workplace simulation was implemented, spanning the entire 12-week duration of the course. The simulation was achieved through the creation of an online company presence, the infusion of communication typically encountered in the workplace, and an intensive and…

Renal contrast-enhanced MR angiography: timing errors and accurate depiction of renal artery origins.

PubMed

Schmidt, Maria A; Morgan, Robert

2008-10-01

To investigate bolus timing artifacts that impair depiction of renal arteries at contrast material-enhanced magnetic resonance (MR) angiography and to determine the effect of contrast agent infusion rates on artifact generation. Renal contrast-enhanced MR angiography was simulated for a variety of infusion schemes, assuming both correct and incorrect timing between data acquisition and contrast agent injection. In addition, the ethics committee approved the retrospective evaluation of clinical breath-hold renal contrast-enhanced MR angiographic studies obtained with automated detection of contrast agent arrival. Twenty-two studies were evaluated for their ability to depict the origin of renal arteries in patent vessels and for any signs of timing errors. Simulations showed that a completely artifactual stenosis or an artifactual overestimation of an existing stenosis at the renal artery origin can be caused by timing errors of the order of 5 seconds in examinations performed with contrast agent infusion rates compatible with or higher than those of hand injections. Lower infusion rates make the studies more likely to accurately depict the origin of the renal arteries. In approximately one-third of all clinical examinations, different contrast agent uptake rates were detected on the left and right sides of the body, and thus allowed us to confirm that it is often impossible to optimize depiction of both renal arteries. In three renal arteries, a signal void was found at the origin in a patent vessel, and delayed contrast agent arrival was confirmed. Computer simulations and clinical examinations showed that timing errors impair the accurate depiction of renal artery origins. (c) RSNA, 2008.

Comparison of analgesic efficacy of four-quadrant transversus abdominis plane (TAP) block and continuous posterior TAP analgesia with epidural analgesia in patients undergoing laparoscopic colorectal surgery: an open-label, randomised, non-inferiority trial.

PubMed

Niraj, G; Kelkar, A; Hart, E; Horst, C; Malik, D; Yeow, C; Singh, B; Chaudhri, S

2014-04-01

Posterior transversus abdominis plane blocks have been reported to be an effective method of providing analgesia after lower abdominal surgery. We compared the efficacy of a novel technique of providing continuous transversus abdominis plane analgesia with epidural analgesia in patients on an enhanced recovery programme following laparoscopic colorectal surgery. A non-inferiority comparison was used. Adult patients undergoing elective laparoscopic colorectal surgery were randomly assigned to receive continuous transversus abdominis plane analgesia (n = 35) vs epidural analgesia (n = 35), in addition to a postoperative analgesic regimen comprising regular paracetamol, regular diclofenac and tramadol as required. Sixty-one patients completed the study. The transversus group received four-quadrant transversus abdominis plane blocks and bilateral posterior transversus abdominis plane catheters that were infused with levobupivacaine 0.25% for 48 h. The epidural group received an infusion of bupivacaine and fentanyl. The primary outcome measure was visual analogue scale pain score on coughing at 24 h after surgery. We found no significant difference in median (IQR [range]) visual analogue scores during coughing at 24 h between the transversus group 2.5 (1.0-3.0 [0-5.5]) and the epidural group 2.5 (1.0-5.0 [0-6.0]). The one-sided 97.5% CI was a 0.0 (∞-1.0) difference in means, establishing non-inferiority. There were no significant differences between the groups for tramadol consumption. Success rate was 28/30 (93%) in the transversus group vs 27/31 (87%) in the epidural group. Continuous transversus abdominis plane infusion was non-inferior to epidural infusion in providing analgesia after laparoscopic colorectal surgery. © 2013 The Association of Anaesthetists of Great Britain and Ireland.

[Using the subcutaneous approach for symptoms control in a health center].

PubMed

Pascual López, L; Portaceli Armiñana, A; Ros Sáez, A

2001-01-01

To describe the use of the subcutaneous tract for symptoms control in patients those are in phase of palliative treatment of their illness. Observational study. Primary care. Patients seen in a health center, in phase of palliative treatment of their illness, that needed for symptoms control the subcutaneous administration of drugs. Most of the patients were in terminal phase (19), the fundamental cause (17 cases) that justified the use of the subcutaneous tract was the difficulty to take drugs by oral tract in the last days of life, attention on death throes. The infusion continuous through injector type travenol, at an infusion speed of 2 ml/h, it was the most common way of drug administration (19 patients). The drugs and initial average dose most used were: morphine 19 patients dose 100 mg/24 h, hyoscine butylbromide (Buscapina), 13 patients, 60 mg/24 h, haloperidol 12 patients, 4 mg/24 h. The patients death was the main cause that justified the retirement of the continuous infusion (17 people sick), happening in its own home. Symptoms control was good or very good in the most of patients (14). The experience on using the subcutaneous tract for symptoms control in our health center is positive, being the fundamental cause for its use symptoms control in the last days of the patients life. The continuous subcutaneous infusion should be used in primary attention, as an usual technique for the symptoms control in patients that are in phase of palliative treatment of their illness.

Comparison of continuous interscalene block and subacromial infusion of local anesthetic for postoperative analgesia after open shoulder surgery.

PubMed

Baskan, Semih; Cankaya, Deniz; Unal, Hidayet; Yoldas, Burak; Taspinar, Vildan; Deveci, Alper; Tabak, Yalcin; Baydar, Mustafa

2017-01-01

This study compared the efficacy of continuous interscalene block (CISB) and subacromial infusion of local anesthetic (CSIA) for postoperative analgesia after open shoulder surgery. This randomized, prospective, double-blinded, single-center study included 40 adult patients undergoing open shoulder surgery. All patients received a standardized general anesthetic. The patients were separated into group CISB and group CSIA. A loading dose of 40 mL 0.25% bupivacaine was administered and patient-controlled analgesia was applied by catheter with 0.1% bupivacaine 5 mL/h throughout 24 h basal infusion, 2 mL bolus dose, and 20 min knocked time in both groups postoperatively. Visual analog scale (VAS) scores, additional analgesia need, local anesthetic consumption, complications, and side effects were recorded during the first 24 h postoperatively. The range of motion (ROM) score was recorded preoperatively and in the first and third weeks postoperatively. A statistically significant difference was determined between the groups in respect of consumption of local anesthetic, VAS scores, additional analgesia consumption, complications, and side effects, with lower values recorded in the CISB group. There were no significant differences in ROM scoring in the preoperative and postoperative third week between the two groups but there were significant differences in ROM scoring in the postoperative first week, with higher ROM scoring values in the group CISB patients. The results of this study have shown that continuous interscalene infusion of bupivacaine is an effective and safe method of postoperative analgesia after open shoulder surgery.

Resin Flow Behavior Simulation of Grooved Foam Sandwich Composites with the Vacuum Assisted Resin Infusion (VARI) Molding Process

PubMed Central

Zhao, Chenhui; Zhang, Guangcheng; Wu, Yibo

2012-01-01

The resin flow behavior in the vacuum assisted resin infusion molding process (VARI) of foam sandwich composites was studied by both visualization flow experiments and computer simulation. Both experimental and simulation results show that: the distribution medium (DM) leads to a shorter molding filling time in grooved foam sandwich composites via the VARI process, and the mold filling time is linearly reduced with the increase of the ratio of DM/Preform. Patterns of the resin sources have a significant influence on the resin filling time. The filling time of center source is shorter than that of edge pattern. Point pattern results in longer filling time than of linear source. Short edge/center patterns need a longer time to fill the mould compared with Long edge/center sources.

Randomized Trial of Infusion Set Function: Steel Versus Teflon

PubMed Central

Patel, Parul J.; Benasi, Kari; Ferrari, Gina; Evans, Mark G.; Shanmugham, Satya; Wilson, Darrell M.

2014-01-01

Abstract Background: This study compared infusion set function for up to 1 week using either a Teflon® (Dupont™, Wilmington, DE) catheter or a steel catheter for insulin pump therapy in type 1 diabetes mellitus. Subjects and Methods: Twenty subjects participating in a randomized, open-labeled, crossover study were asked to wear two Quick-Set® and two Sure-T® infusion sets (both from Medtronic Minimed, Northridge, CA) until the infusion set failed or was worn for 1 week. All subjects wore a MiniMed continuous glucose monitoring system for the duration of the study. Results: One subject withdrew from the study. There were 38 weeks of Sure-T wear and 39 weeks of Quick-Set wear with no difference in the survival curves of the infusion sets. There was, however, a 15% initial failure rate with the Teflon infusion set. After 7 days, both types of infusion sets had a 64% failure rate. Overall, 30% failed because of hyperglycemia and a failed correction dose, 13% were removed for pain, 10% were pulled out by accident, 10% had erythema and/or induration of>10 mm, 5% fell out because of loss of adhesion, and 4% were removed for infection. The main predictor of length of wear was the individual subject. There was no increase in hyperglycemia or daily insulin requirements when an infusion set was successfully used for 7 days (n=25 of 77 weeks). Conclusions: We found no difference between steel and Teflon infusion sets in their function over 7 days, although 15% of Teflon sets failed because of kinking on insertion. The strongest predictor of prolonged 7-day infusion set function was the individual subject, not the type of infusion set. PMID:24090124

Intraarticular vs. extraarticular ropivacaine infusion following high-dose local infiltration analgesia after total knee arthroplasty

PubMed Central

2011-01-01

Background and purpose Ropivacaine infusion following high-volume local infiltration analgesia has been shown to be effective after total knee arthroplasty, but the optimum site of administration of ropivacaine has not been evaluated. We compared the effects of intraarticular and extraarticular adminstration of the local anesthetic for postoperative supplementation of high-volume local infiltration analgesia. Patients and methods In this double-blind study, 36 rheumatic patients aged 51–78 years with physical status ASA 2–3 who were scheduled for total knee arthroplasty were randomized into 2 groups. All patients received wound infiltration at the end of surgery with 300 mg ropivacaine, 30 mg ketorolac, and 0.5 mg epinephrine (total volume 156 mL). A tunneled catheter was randomly placed either extraarticularly or intraarticularly. Continuous infusion of ropivacain (0.5%, 2 mL/h) was started immediately and was maintained during the next 48 h. Pain intensity at rest, on movement, and with mobilization was estimated by the patients and the physiotherapist; rescue morphine consumption was recorded. Results As estimated by the patients, ropivacaine administered intraarticularly did not improve analgesia relative to extraarticular infusion, but improved the first mobilization. The incidence of high intensity of pain (VAS 7–10) was less in the group with intraarticular infusion. Analgesic requirements were similar in the 2 groups (47 mg and 49 mg morphine). No complications of postoperative wound healing were seen and there were no toxic side effects. Interpretation Continuous infusion of ropivacaine intraarticulary did not improve postoperative analgesia at rest relative to extraarticular administration, but it appeared to reduce the incidence of high pain intensity during first exercises, and could therefore be expected to improve mobilization up to 24 h after total knee arthroplasty. PMID:22026413

The Effect of a Subcutaneous Infusion of GLP-1, OXM, and PYY on Energy Intake and Expenditure in Obese Volunteers

PubMed Central

Tan, Tricia; Behary, Preeshila; Tharakan, George; Minnion, James; Al-Najim, Werd; Albrechtsen, Nicolai J. Wewer; Holst, Jens J.

2017-01-01

Background: Roux-en-Y gastric bypass (RYGB) surgery is currently the most effective treatment of obesity, although limited by availability and operative risk. The gut hormones Glucagon-like peptide-1 (GLP-1), Peptide YY (PYY), and Oxyntomodulin (OXM) are elevated postprandially after RYGB, which has been postulated to contribute to its metabolic benefits. Objective: We hypothesized that infusion of the three gut hormones to achieve levels similar to those encountered postprandially in RYGB patients might be effective in suppressing appetite. The aim of this study was to investigate the effect of a continuous infusion of GLP-1, OXM, and PYY (GOP) on energy intake and expenditure in obese volunteers. Methods: Obese volunteers were randomized to receive an infusion of GOP or placebo in a single-blinded, randomized, placebo-controlled crossover study for 10.5 hours a day. This was delivered subcutaneously using a pump device, allowing volunteers to remain ambulatory. Ad libitum food intake studies were performed during the infusion, and energy expenditure was measured using a ventilated hood calorimeter. Results: Postprandial levels of GLP-1, OXM, and PYY seen post RYGB were successfully matched using 4 pmol/kg/min, 4 pmol/kg/min, and 0.4 pmol/kg/min, respectively. This dose led to a mean reduction of 32% in food intake. No significant effects on resting energy expenditure were observed. Conclusion: This is, to our knowledge, the first time that an acute continuous subcutaneous infusion of GOP, replicating the postprandial levels observed after RYGB, is shown to be safe and effective in reducing food intake. This data suggests that triple hormone therapy might be a useful tool against obesity. PMID:28379519

Comparison between analgesic effect of bupivacaine thoracic epidural and ketamine infusion plus wound infiltration with local anesthetics in open cholecystectomy.

PubMed

Megahed, Nagwa Ahmed Ebrahim; Ellakany, Mohamed; Elatter, Ahmed Mohammed Ibrahim; Moustafa Teima, Mohamed Ahmed Ali

2014-01-01

Neuraxial blocks result in sympathetic block, sensory analgesia and motor block. Continuous epidural anesthesia through a catheter offers several options for perioperative analgesia. Local anesthetic boluses or infusions can provide profound analgesia. Although the role of low-dose ketamine (<2 mg/kg intramuscular, <1 mg/kg intravenous [IV] or ≤ 20 μg/kg/min by IV infusion) in the treatment of post-operative pain is controversial, perioperative administration of a small dose of ketamine may be valuable to a multimodal analgesic regimen. A local anesthetic can be used for wound infiltration intra-operative to minimized the surgical pain. A prospective randomized study was performed in which 40 patients scheduled for elective open cholecystectomy under general anesthesia admitted to the Medical Research Institute were included and further subdivided into two groups, group A, received thoracic epidural catheter at T7-8, activation was done 20 min before induction of anesthesia with plain bupivacaine at a concentration of 0.25% at a volume of 1 ml/segment aiming to block sensory supply from T4-L2, then received continuous thoracic epidural infusion intra and postoperatively with plain bupivacaine at a concentration of 0.125% at a rate of 5 ml/h for 24 h, group B received 0.3 mg/kg bolus of ketamine at the time of induction then 0.1 mg/kg/h ketamine IV infusion during surgery followed by wound infiltration with 15 ml of plain bupivacaine 0.5% at the time of skin closure. Bupivacaine thoracic epidural analgesia had better control on heart rate and mean arterial blood pressure than ketamine infusion plus wound infiltration with local anesthetic in patients undergoing open cholecystectomy. Thoracic epidural analgesia had better control on hemodynamic changes intra-and postoperatively than ketamine infusion with local wound infiltration in open cholecystectomy.

Evidence for Increased Beta-Adrenoreceptor Responsiveness Induced by 14 Days of Simulated Microgravity in Humans

NASA Technical Reports Server (NTRS)

Convertino, Victor A.; Polet, Jill L.; Engelke, Keith A.; Hoffler, G. W.; Lane, Lynda D.

1996-01-01

We studied hemodynamic responses to alpha and beta receptor agonists in 8 healthy men ( 38+- 2 yrs) before and after 14 days of 6 degree head-down tilt (HDT) to test the hypothesis that increased adrenergic responsiveness is induced by prolonged exposure to microgravity. Immediately following a 30-min baseline period, a steady-state infusion of isoproterenol (ISO) was used to assess beta 1- and beta 2-adrenergic responsiveness. ISO was infused at three graded constant rates of 0.005, 0.01 and 0.02 ug/kg/min. After heart rate and blood pressure had been allowed to return to baseline levels following ISO infusion graded infusion of phenylephrine (PE) was used to assess responsiveness of alpha I-vascular receptors. PE was infused at three graded constant rates of 0.25, 0.50 and 1.00 ug/kg/min. Each infusion interval for both drugs was 9 min. During the infusions, constant monitoring of beat-to-beat blood pressure and heart rate was performed and leg blood flow was measured with occlusion plethysmography at each infusion level. The slopes calculated from linear regressions between ISO and PE doses and changes in heart rate, blood pressure, and leg vascular resistance for each subject were used to represent alpha- and beta- adrenoreceptor responsiveness. Fourteen days HDT increased the slopes of heart rate (1056 +- 107 to 1553 +- 83 beats/ug/kg/min; P= 0.014) and vasodilation (-469ft +- 111 to -l446 +- 309 PRU/ug/kg/min; P =0.0224) to ISO infusion. There was no alteration in blood pressure or vascular resistance responses to PE infusion after HDT. Our results provide evidence that microgravity causes selective increases in beta 1- and beta 2-adrenergic responsiveness without affecting alpha 1-vascular responses.

Effect of cortisol infusion patterns and castration on metabolic and immunological indices of stress response in cattle.

PubMed

Ting, S T L; Earley, B; Crowe, M A

2004-05-01

This study tested the hypotheses that: (1) either acute stress induced by Burdizzo castration, or cortisol infusion would modulate plasma glucose, insulin and growth hormone (GH) concentrations; and (2) immune modulation induced by cortisol would be dependent on the pattern, intensity and duration of circulating cortisol concentrations. Fifty 9.2-month-old Holstein x Friesian bulls (232 +/- 2.0 kg) were blocked by weight and randomly assigned to one of five treatments (n = 10 per treatment): (1) sham handled control; (2) Burdizzo castration; (3) hydrocortisone infusion to mimic the castration-induced secretion pattern of cortisol; (4) hourly pulse infusion of hydrocortisone; and (5) sustained infusion of hydrocortisone for 8h. Blood samples were collected intensively on day 0, and weekly from days 1 to 35. Castration acutely increased plasma cortisol, GH and haptoglobin concentrations, suppressed lymphocyte in vitro interferon-gamma (IFN-gamma) production, but had no effect on plasma glucose and insulin concentrations. Cortisol infusion to simulate the castration-induced secretion pattern of cortisol, and pulse infusion of cortisol did not suppress the IFN-gamma production. A sustained infusion of cortisol resulted in the transient suppression of IFN-gamma production. Moreover, the sustained cortisol infusion resulted in increased plasma glucose, insulin and GH concentrations. The overall 14-day feed intakes and 35-day growth rates were not affected by treatments. In conclusion, cortisol infusion to induce immune suppression in vivo occurred only at pharmacological doses. Within physiological ranges, cortisol was not associated with the suppression of immune function, indicating that during castration cortisol per se is not responsible for the suppression of in vitro IFN-gamma production.

An assessment of the variation in the concentration of acetylcysteine in infusions for the treatment of paracetamol overdose

PubMed Central

Bailey, George P.; Wood, David M.; Archer, John R. H.; Rab, Edmund; Flanagan, Robert J.

2016-01-01

Background Intravenous acetylcysteine is the treatment of choice for paracetamol poisoning. A previous UK study in 2001 found that 39% of measured acetylcysteine infusion concentrations differed by >20% from anticipated concentrations. In 2012, the UK Commission on Human Medicines made recommendations for the management of paracetamol overdose, including provision of weight‐based acetylcysteine dosing tables. The aim of this study was to assess variation in acetylcysteine concentrations in administered infusions following the introduction of this guidance. Methods A 6‐month single‐centre prospective study was undertaken at a UK teaching hospital. After preparation, 5‐ml samples were taken from the first, second and third/any subsequent acetylcysteine infusions. Acetylcysteine was measured in diluted (1:50) samples by high‐performance liquid chromatography. Comparisons between measured and expected concentrations based on prescribed weight‐based dose and volume were made for each infusion. Results Ninety samples were collected. There was a variation of ≤10% in measured compared to expected concentration for 45 (50%) infusions, of 10–20% for 27 (30%) infusions, 20.1–50% for 14 (16%) infusions and >50% for four (4%) infusions. There was a median (interquartile range) variation in measured compared to expected concentration of −3.6 mg ml−1 (−6.7 to −2.3) for the first infusion, +0.2 mg ml−1 (−0.9 to +0.4) for the second infusion and −0.3 mg ml−1 (−0.6 to +0.2) for third and fourth infusions. Conclusion There has been a moderate improvement in the variation in acetylcysteine dose administered by infusion. Further work is required to understand the continuing variation and consideration should be given to simplification of acetylcysteine regimes to decrease the risk of administration errors. PMID:27558662

Air elimination capability in rapid infusion systems.

PubMed

Zoremba, N; Gruenewald, C; Zoremba, M; Rossaint, R; Schaelte, G

2011-11-01

Pressure infusion devices are used in clinical practice to apply large volumes of fluid over a short period of time. Although air infusion is a major complication, they have limited capability to detect and remove air during pressure infusion. In this investigation, we tested the air elimination capabilities of the Fluido(®) (The Surgical Company), Level 1(®) (Level 1 Technologies Inc.) and Ranger(®) (Augustine Medical GmbH) pressure infusion devices. Measurements were undertaken with a crystalloid solution during an infusion flow of 100, 200, 400 and 800 ml.min(-1). Four different volumes of air (25, 50, 100 and 200 ml) were injected as boluses in one experimental setting, or infused continuously over the time needed to perfuse 2 l saline in the other setting. The perfusion fluid was collected in an airtight infusion bag and the amount of air obtained in the bag was measured. The delivered air volume was negligible and would not cause any significant air embolism in all experiments. In our experimental setting, we found, during high flow, an increased amount of uneliminated air in all used devices compared with lower perfusion flows. All tested devices had a good air elimination capability. The use of ultrasonic air detection coupled with an automatic shutoff is a significant safety improvement and can reliably prevent accidental air embolism at rapid flows. © 2011 The Authors. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.

Antioxidant capacity and polyphenolic content of blueberry (Vaccinium corymbosum L.) leaf infusions.

PubMed

Piljac-Zegarac, J; Belscak, A; Piljac, A

2009-06-01

Antioxidant capacity and polyphenolic content of leaf infusions prepared from six highbush blueberry cultivars (Vaccinium corymbosum L.), one wild lowbush blueberry cultivar (Vaccinium myrtillus L.), and one commercially available mix of genotypes were determined. In order to simulate household tea preparation conditions, infusions were prepared in water heated to 95 degrees C. The dynamics of extraction of polyphenolic antioxidants were monitored over the course of 30 minutes. Extraction efficiency, quantified in terms of the total phenol (TP) content, and antioxidant capacity of infusions, evaluated by the ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging assays, were compared with cultivar type and extraction time. The 30-minute infusions exhibited the highest TP content and antioxidant capacity according to all three assays. Wild blueberry infusion had the highest TP content (1,879 mg/L gallic acid equivalents [GAE]) and FRAP values (20,050 microM). The range of TP values for 30-minute infusions was 394-1,879 mg/L GAE with a mean of 986 mg/L GAE across cultivars; FRAP values fell between 3,015 and 20,050 microM with a mean of 11,234 microM across cultivars. All 30-minute infusions exhibited significant scavenging capacity for DPPH(*) and ABTS(*+) radicals, comparable to different concentrations of catechin, gallic acid, and 6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid. Overall, tested infusions showed significant reducing capacity as well as radical scavenging potential, which places blueberry leaf tea high on the list of dietary sources of antioxidants.

Combining Basal–Bolus Insulin Infusion for Tight Postprandial Glucose Control: An in Silico Evaluation in Adults, Children, and Adolescents

PubMed Central

Revert, Ana; Rossetti, Paolo; Calm, Remei; Vehí, Josep; Bondia, Jorge

2010-01-01

Background Achieving good postprandial glycemic control, without triggering hypoglycemia events, is a challenge of treatment strategies for type 1 diabetes subjects. Continuous subcutaneous insulin infusion, the gold standard of therapy, is based on heuristic adjustments of both basal and prandial insulin. Some tools, such as bolus calculators, are available to aid patients in selecting a meal-related insulin dose. However, they are still based on empiric parameters such as the insulin-to-carbohydrate ratio and on the physicians’ and patients’ ability to fit bolus mode to meal composition. Method In this article, a nonheuristic method for assessment of prandial insulin administration is presented and evaluated. An algorithm based on set inversion via interval analysis is used to coordinate basal and bolus insulin infusions to deal with postprandial glucose excursions. The evaluation is carried out through an in silico study using the 30 virtual patients available in the educational version of the Food and Drug Administration-accepted University of Virginia simulator. Results obtained using the standard bolus strategy and different coordinated basal–bolus solutions provided by the algorithm are compared. Results Coordinated basal–bolus solutions improve postprandial glucose performance in most cases, mainly in terms of reducing hypoglycemia risk, but also increasing the percentage of time in normoglycemia. Moreover, glycemic variability is reduced considerably by using these innovative solutions. Conclusions The algorithm presented here is a robust nonheuristic alternative to deal with postprandial glycemic control. It is shown as a powerful tool that could be integrated in future smart insulin pumps. PMID:21129338

Orthopaedic wear particle-induced bone loss and exogenous macrophage infiltration is mitigated by local infusion of NF-κB decoy oligodeoxynucleotide.

PubMed

Lin, Tzuhua; Pajarinen, Jukka; Nabeshima, Akira; Córdova, Luis A; Loi, Florence; Gibon, Emmanuel; Lu, Laura; Nathan, Karthik; Jämsen, Eemeli; Yao, Zhenyu; Goodman, Stuart B

2017-11-01

Excessive production of wear particles from total joint replacements induces chronic inflammation, macrophage infiltration, and consequent bone loss (periprosthetic osteolysis). This inflammation and bone remodeling are critically regulated by the transcription factor NF-κB. We previously demonstrated that inhibition of NF-κB signaling by using the decoy oligodeoxynucleotide (ODN) mitigates polyethylene wear particle-induced bone loss using in vitro and in vivo models. However, the mechanisms of NF-κB decoy ODN action, and in particular its impact on systemic macrophage recruitment, remain unknown. In the current study, this systemic macrophage infiltration was examined in our established murine femoral continuous particle infusion model. RAW264.7 murine macrophages expressing a luciferase reporter gene were injected into the systemic circulation. Quantification of bioluminescence showed that NF-κB decoy ODN reduced the homing of these reporter macrophages into the distal femurs exposed to continuous particle delivery. Particle-induced reduction in bone mineral density at the distal diaphysis of the femur was also mitigated by infusion of decoy ODN. Histological staining showed that the decoy ODN infusion decreased osteoclast and macrophage numbers, but had no significant effects on osteoblasts. Local infusion of NF-κB decoy ODN reduced systemic macrophage infiltration and mitigated particle-induced bone loss, thus providing a potential strategy to treat periprosthetic osteolysis. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3169-3175, 2017. © 2017 Wiley Periodicals, Inc.

Physical stability of 20% lipid injectable emulsions via simulated syringe infusion: effects of glass vs plastic product packaging.

PubMed

Driscoll, David F; Ling, Pei-Ra; Bistrian, Bruce R

2007-01-01

The United States Pharmacopeia (USP) has proposed large-globule-size limits to ensure the physical stability of lipid injectable emulsions, expressed as the percent fat >5 microm, or PFAT(5), not exceeding 0.05%. Visibly obvious phase separation as free oil has been shown to occur in some samples if PFAT(5) is >0.4%. We recently found that lipids, newly packaged in plastic (P), exceed the proposed USP limits and seem to produce less stable total nutrient admixtures compared with those made from conventional glass (G), which do meet proposed USP standards. We tested the possible stability differences between 20% lipid injectable emulsions in either P or G in a simulated neonatal syringe infusion study. Eighteen individual syringes were prepared from each 20% lipid injectable emulsion product (n = 36) and attached to a syringe pump set at an infusion rate of 0.5 mL/hour. The starting PFAT(5) levels were measured at time 0 and after 24 hours of infusion, using a laser-based light obscuration technique as described by the USP Chapter <729>. The data were assessed by a 2-way analysis of variance (ANOVA) with Container (G vs P) and Time as the independent variables and PFAT as the dependent variable. At time 0, the starting PFAT(5) level for lipids packaged in G was 0.006% +/- 0.001% vs 0.162% +/- 0.026% for P, whereas at the end of the infusion they were 0.013% +/- 0.003% and 0.328% +/- 0.046%, respectively. Significant differences were noted overall between groups for Container, Time, and Container-Time interaction (all p < .001). Bonferroni tests showed significant differences in PFAT(5) levels between Containers at time 0 (T-0; p < .001) and T-0 vs T-24 for P-based lipids (p < .001), whereas no such differences were noted for Time for the G-based lipids. Similar results were noted for PFAT(10) levels. We confirm that presently available lipid injectable emulsions packaged in newly introduced plastic containers exceed the proposed USP <729> PFAT(5) limits and subsequently become significantly less stable during a simulated syringe-based infusion. Although modest growth (p = NS) in large-diameter fat globules was observed for the glass-based lipids, they remained within proposed USP globule size limits throughout the study. Glass-based lipids seem to be a more stable dosage form and potentially a safer way to deliver lipids via syringe infusion to critically ill neonates.

The human anterior lens capsule--an attempted chemical debridement of epithelial cells by ethylenediaminetetracetic acid (EDTA) and trypsin.

PubMed Central

Humphry, R C; Davies, E G; Jacob, T J; Thompson, G M

1988-01-01

The addition of edetic acid (EDTA) or trypsin to the infusion during a simulated extracapsular cataract extraction on cadaver eyes facilitates the removal of lens epithelial cells from the anterior capsule. Modification of the chemical composition of infusions used during extracapsular surgery may maximise lens epithelial cell removal and hence reduce the incidence of opacification of the posterior capsule after cataract extraction. Images PMID:3134044

[Pain control by continuous infusion of morphine using subarachnoid catheter access to the port--a report of a home death case].

PubMed

Kawagoe, Koh; Matsuura, Shinobu

2008-12-01

This is a case of a 50s male with cecal cancer suffering from severe pain caused by osteolytic metastasis to the lumbar vertebra, right iliac bone, and the head of the right femur. The pain was palliated by continuous infusion of morphine using a subarachnoid catheter that had access to the subcutaneous "Port". The maximum dose of morphine used a day was 384 mg, which corresponded to 57,600 mg/day of oral morphine. Sixty eight days after the start of home hospice care, the patient died at home because of diffuse peritonitis caused by intestinal rupture.

Relative Incidence of Phlebitis Caused by Continuous Intravenous Infusion of Cephapirin and Cephalothin

PubMed Central

Lane, A. Z.; Taggart, J. G.; Iles, R. L.

1972-01-01

In a single-blinded study, two groups of 10 healthy subjects were given cephapirin or cephalothin by continuous intravenous infusion for 5 days, 0.5 g every 6 hr for the first day and then 1.0 g every 6 hr for 4 days. Eight of the cephalothin subjects and two of the cephapirin subjects developed phlebitis. Phlebitis was more severe in the cephalothin group and developed more rapidly, necessitating vein changes six times more often than in the cephapirin group. The less irritating properties of cephapirin demonstrated in this study indicate it may be the more useful cephalosporin analogue for intravenous therapy. PMID:4790563

NK-1 receptor desensitization and neutral endopeptidase terminate SP-induced pancreatic plasma extravasation.

PubMed

Maa, J; Grady, E F; Kim, E H; Yoshimi, S K; Hutter, M M; Bunnett, N W; Kirkwood, K S

2000-10-01

Substance P (SP) induces plasma extravasation and neutrophil infiltration by activating the neurokinin-1 receptor (NK1-R). We characterized the mechanisms regulating this response in the rat pancreas. Anesthetized rats were continuously infused with SP, and plasma extravasation was quantified using Evans blue (EB) dye. Continuous infusion of SP (8 nmol. kg(-1). h(-1)) resulted in a threshold increase in EB at 15 min, a peak effect at 30 min (150% increase), and a return to baseline by 60 min. The NK1-R antagonist CP-96,345 blocked SP-induced plasma extravasation. After 60 min, the NK1-R was desensitized to agonist challenge. Resensitization was first detected at 20 min and increased until full recovery was seen at 30 min. Inhibition of the cell-surface protease neutral endopeptidase (NEP) by phosphoramidon potentiated the effect of exogenous SP; therefore endogenous NEP attenuates SP-induced plasma extravasation. Thus the continuous infusion of SP stimulates plasma extravasation in the rat pancreas via activation of the NK1-R, and these effects are terminated by both desensitization of the NK1-R and the cell-surface protease NEP.

Sustained benefit of continuous subcutaneous insulin infusion on glycaemic control and hypoglycaemia in adults with Type 1 diabetes.

PubMed

Beato-Víbora, P; Yeoh, E; Rogers, H; Hopkins, D; Amiel, S A; Choudhary, P

2015-11-01

To evaluate the sustainability of the benefits of continuous subcutaneous insulin infusion therapy in routine practice in a cohort of adults with diabetes. The clinical records of all adults starting continuous subcutaneous insulin infusion over 12 years at our centre were included in this study. Baseline and mean annual HbA(1c) levels were recorded. The frequency of mild-to-moderate and severe hypoglycaemia and hypoglycaemia awareness were analysed in a subgroup. Adequate data were available from 327 patients, of whom 71% were female. The patients' mean ± sd age was 41 ± 14 years, the mean ± sd (range) follow-up for continuous subcutaneous insulin infusion was 4.3 ± 2.7 (1-12) years. The mean ± sd HbA(1c) concentration fell by 8 ± 5 mmol/mol (0.7 ± 0.5%) at year 1 [to 63 ± 12 mmol/mol from 70 ± 18 mmol/mol (7.9 ± 1.1% from 8.6 ± 1.6%); P < 0.0005], sustained to year 5. In patients with initial poor control, HbA(1c) dropped by 12 ± 11 mmol/mol (1.1 ± 1.0%; P < 0.0005) at year 1, sustained to year 6. The percentage of patients with ≥ 5 mild to moderate hypoglycaemic episodes per week fell from 29 to 12% (n = 163; P = 0.006). In the subgroup (n = 87; follow-up 2.5 ± mean ± sd 1.1 years), the frequency of severe hypoglycaemia fell from 0.6 ± 1.7 episodes per patient per year to 0.3 ± 0.9 (P = 0.047). Of 24 patients with impaired awareness of hypoglycaemia (Gold score ≥ 4), the mean ± sd Gold score improved from 4.9 ± 0.9 to 3.8 ± 1.7 (P = 0.011). Nine people regained awareness. No deterioration in HbA(1c) was seen in the hypoglycaemia-prone groups. The benefits of continuous subcutaneous insulin infusion with regard to improving glycaemic control and reducing hypoglycaemia frequency, along with improvement in hypoglycaemia awareness without deterioration in glycaemic control, can be sustained over several years in clinical practice. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

The calcitonin gene-related peptide receptor antagonist MK-8825 decreases spinal trigeminal activity during nitroglycerin infusion.

PubMed

Feistel, Stephan; Albrecht, Stephanie; Messlinger, Karl

2013-11-20

Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are regarded as key mediators in migraine and other primary headaches. Migraineurs respond to infusion of nitroglycerin with delayed headaches, and inhibition of CGRP receptors has been shown to be effective in migraine therapy. In animal experiments nitrovasodilators like nitroglycerin induced increases in spinal trigeminal activity, which were reversed after inhibition of CGRP receptors. In the present study we asked if CGRP receptor inhibition can also prevent spinal trigeminal activity induced by nitroglycerin. In isoflurane anaesthetised rats extracellular recordings were made from neurons in the spinal trigeminal nucleus with meningeal afferent input. The non-peptide CGRP receptor inhibitor MK-8825 (5 mg/kg) dissolved in acidic saline (pH 3.3) was slowly infused into rats one hour prior to prolonged glyceryl trinitrate (nitroglycerin) infusion (250 μg/kg/h for two hours). After infusion of MK-8825 the activity of spinal trigeminal neurons with meningeal afferent input did not increase under continuous nitroglycerin infusion but decreased two hours later below baseline. In contrast, vehicle infusion followed by nitroglycerin was accompanied by a transient increase in activity. CGRP receptors may be important in an early phase of nitroglycerin-induced central trigeminal activity. This finding may be relevant for nitroglycerin-induced headaches.

Technology, Pedagogy, and Epistemology: Opportunities and Challenges of Using Computer Modeling and Simulation Tools in Elementary Science Methods

ERIC Educational Resources Information Center

Schwarz, Christina V.; Meyer, Jason; Sharma, Ajay

2007-01-01

This study infused computer modeling and simulation tools in a 1-semester undergraduate elementary science methods course to advance preservice teachers' understandings of computer software use in science teaching and to help them learn important aspects of pedagogy and epistemology. Preservice teachers used computer modeling and simulation tools…

APIC position paper: Safe injection, infusion, and medication vial practices in health care.

PubMed

Dolan, Susan A; Arias, Kathleen Meehan; Felizardo, Gwen; Barnes, Sue; Kraska, Susan; Patrick, Marcia; Bumsted, Amelia

2016-07-01

The transmission of bloodborne viruses and other microbial pathogens to patients during routine health care procedures continues to occur because of the use of improper injection, infusion, medication vial, and point-of-care testing practices by health care personnel. These unsafe practices occur in various clinical settings and result in unacceptable and devastating events for patients. This document updates the Association for Professionals in Infection Control and Epidemiology 2010 position paper on safe injection, infusion, and medication vial practices in health care. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

An intravenous medication safety system: preventing high-risk medication errors at the point of care.

PubMed

Hatcher, Irene; Sullivan, Mark; Hutchinson, James; Thurman, Susan; Gaffney, F Andrew

2004-10-01

Improving medication safety at the point of care--particularly for high-risk drugs--is a major concern of nursing administrators. The medication errors most likely to cause harm are administration errors related to infusion of high-risk medications. An intravenous medication safety system is designed to prevent high-risk infusion medication errors and to capture continuous quality improvement data for best practice improvement. Initial testing with 50 systems in 2 units at Vanderbilt University Medical Center revealed that, even in the presence of a fully mature computerized prescriber order-entry system, the new safety system averted 99 potential infusion errors in 8 months.

Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy.

PubMed

Brown, Christine E; Alizadeh, Darya; Starr, Renate; Weng, Lihong; Wagner, Jamie R; Naranjo, Araceli; Ostberg, Julie R; Blanchard, M Suzette; Kilpatrick, Julie; Simpson, Jennifer; Kurien, Anita; Priceman, Saul J; Wang, Xiuli; Harshbarger, Todd L; D'Apuzzo, Massimo; Ressler, Julie A; Jensen, Michael C; Barish, Michael E; Chen, Mike; Portnow, Jana; Forman, Stephen J; Badie, Behnam

2016-12-29

A patient with recurrent multifocal glioblastoma received chimeric antigen receptor (CAR)-engineered T cells targeting the tumor-associated antigen interleukin-13 receptor alpha 2 (IL13Rα2). Multiple infusions of CAR T cells were administered over 220 days through two intracranial delivery routes - infusions into the resected tumor cavity followed by infusions into the ventricular system. Intracranial infusions of IL13Rα2-targeted CAR T cells were not associated with any toxic effects of grade 3 or higher. After CAR T-cell treatment, regression of all intracranial and spinal tumors was observed, along with corresponding increases in levels of cytokines and immune cells in the cerebrospinal fluid. This clinical response continued for 7.5 months after the initiation of CAR T-cell therapy. (Funded by Gateway for Cancer Research and others; ClinicalTrials.gov number, NCT02208362 .).

Cardiovascular, respiratory, electrolyte and acid-base balance during continuous dexmedetomidine infusion in anesthetized dogs.

PubMed

Congdon, Jonathan M; Marquez, Megan; Niyom, Sirirat; Boscan, Pedro

2013-09-01

To evaluate the cardiovascular, respiratory, electrolyte and acid-base effects of a continuous infusion of dexmedetomidine during propofol-isoflurane anesthesia following premedication with dexmedetomidine. Prospective experimental study. Five adult male Walker Hound dogs 1-2 years of age averaging 25.4 ± 3.6 kg. Dogs were sedated with dexmedetomidine 10 μg kg(-1) IM, 78 ± 2.3 minutes (mean ± SD) before general anesthesia. Anesthesia was induced with propofol (2.5 ± 0.5 mg kg(-1) ) IV and maintained with 1.5% isoflurane. Thirty minutes later dexmedetomidine 0.5 μg kg(-1) IV was administered over 5 minutes followed by an infusion of 0.5 μg kg(-1)  hour(-1) . Cardiac output (CO), heart rate (HR), ECG, direct blood pressure, body temperature, respiratory parameters, acid-base and arterial blood gases and electrolytes were measured 30 and 60 minutes after the infusion started. Data were analyzed via multiple linear regression modeling of individual variables over time, compared to anesthetized baseline values. Data are presented as mean ± SD. No statistical difference from baseline for any parameter was measured at any time point. Baseline CO, HR and mean arterial blood pressure (MAP) before infusion were 3.11 ± 0.9 L minute(-1) , 78 ± 18 beats minute(-1) and 96 ± 10 mmHg, respectively. During infusion CO, HR and MAP were 3.20 ± 0.83 L minute(-1) , 78 ± 14 beats minute(-1) and 89 ± 16 mmHg, respectively. No differences were found in respiratory rates, PaO2 , PaCO2 , pH, base excess, bicarbonate, sodium, potassium, chloride, calcium or lactate measurements before or during infusion. Dexmedetomidine infusion using a loading dose of 0.5 μg kg(-1) IV followed by a constant rate infusion of 0.5 μg kg(-1)  hour(-1) does not cause any significant changes beyond those associated with an IM premedication dose of 10 μg kg(-1) , in propofol-isoflurane anesthetized dogs. IM dexmedetomidine given 108 ± 2 minutes before onset of infusion showed typical significant effects on cardiovascular parameters. © 2013 The Authors. Veterinary Anaesthesia and Analgesia © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Protein delivery with infusion pumps.

PubMed

Bremer, U; Horres, C R; Francoeur, M L

1997-01-01

When a therapeutic effect is optimized by precise control of specific temporal patterns of plasma levels, infusion offers distinct advantages over oral administration, bolus injection, or depot delivery of polypeptides. The limitations of oral delivery are well known, and although research is under way into development of carrier systems that prevent degradation of labile agents, it is unlikely that the variances in absorption will meet the need for precise control. Depot delivery from subcutaneous or intramuscular implants presents a difficult situation when local tissue reactions to the agent sometimes occur. Removal of a depot system in the event of adverse reactions presents additional difficulties. Bolus injections are unable to sustain constant plasma levels unless the drug half-life is long or the injections are frequently administered. Insulin injections, for example, would be required every 30-60 minutes to approximate the plasma levels provided by a continuous infusion; such frequent injections would not be practical on a 24-hour basis. For the developer of new polypeptides, parenteral administration offers the most direct route to the marketplace. The step from periodic injections to tightly controlled infusion is a logical progression as compared with modification of the molecules or vehicles to obtain equivalent profiles. In Table II several different types of devices that can be used for infusion of proteins are compared. Microelectronics have played a major role in the miniaturization of infusion devices and undoubtedly will continue to do so. Micromachining, a spin-off technology of integrated circuit manufacture, will also find application in small infusion devices. In the future, we will have cost-effective disposable devices (Saaman et al., 1994) built on this technology that are programmable and thus can be adapted to meet each individual therapeutic need (Horres, 1994). We can also expect to see more closed-loop drug delivery systems where biosensors and infusion devices are combined to optimize a particular therapy. Recent positive results obtained in diabetics by a decade on tight glucose control may forecast a resurgence of popularity of insulin pumps. At the other end of the spectrum, low-cost, small, and simple-to-use osmotically powered systems are close to being marketed; these systems will make infusion almost as convenient as transdermal patches. We will also see major advances in how drugs and devices are interfaced. Prefilled and ready-to-use drug cartridges have proven to be efficient in surgical and emergency medicine and can greatly improve most infusion applications. It is anticipated that coded, prefilled cartridges or pouches will be automatically, recognized by preprogrammed pumps to reduce operator labor and entry error.

Cardiovascular studies using the chimpanzee (Pan troglodytes)

NASA Technical Reports Server (NTRS)

Hinds, J. E.; Cothran, L. N.; Hawthorne, E. W.

1977-01-01

Despite the phylogenetic similarities between chimpanzees and man, there exists a paucity of reliable data on normal cardiovascular function and the physiological responses of the system to standard interventions. Totally implanted biotelemetry systems or hardwire analog techniques were used to examine the maximum number of cardiovascular variables which could be simultaneously monitored without significantly altering the system's performance. This was performed in order to acquire base-line data not previously obtained in this species, to determine cardiovascular response to specific forcing functions such as ventricular pacing, drug infusions, and lower body negative pressure. A cardiovascular function profile protocol was developed in order to adjust independently the three major factors which modify ventricular performance, namely, left ventricular performance, left ventricular preload, afterload, and contractility. Cardiac pacing at three levels above the ambient rate was used to adjust end diastolic volume (preload). Three concentrations of angiotensin were infused continuously to evaluate afterload in a stepwide fashion. A continuous infusion of dobutamine was administered to raise the manifest contractile state of the heart.

Use of ketorolac by continuous subcutaneous infusion for the control of cancer-related pain.

PubMed Central

Myers, K. G.; Trotman, I. F.

1994-01-01

Ketorolac tromethamine is a newly available non-steroidal anti-inflammatory drug which is suitable for parenteral administration. We have given it by continuous subcutaneous infusion to 36 patients with pain due to advanced cancer. Improvement in pain control occurred in 29 (80%). A reduction in the dose of concomitant opioid analgesia was possible in 22 (76%) and a reduction in opioid-related adverse effects occurred in 16 (73%) of these. Ketorolac was most effective in patients who had bone or visceral pain. It was mixed safely with diamorphine in a syringe driver at concentrations up to 4 g diamorphine/10 ml and 120 mg ketorolac/10 ml. Infusion was well tolerated for periods of up to 115 days (mean 21 days; median 15 days; range 3-115 days). Four patients experienced gastrointestinal bleeding and one colonic perforation to which treatment with ketorolac may have been a contributory factor. No other clinically significant adverse effects were observed. PMID:8016008

Alarm Limits for Intraoperative Drug Infusions: A Report From the Multicenter Perioperative Outcomes Group.

PubMed

Berman, Mitchell F; Iyer, Nikhil; Freudzon, Leon; Wang, Shuang; Freundlich, Robert E; Housey, Michelle; Kheterpal, Sachin

2017-10-01

Continuous medication infusions are commonly used during surgical procedures. Alarm settings for infusion pumps are considered important for patient safety, but limits are not created in a standardized manner from actual usage data. We estimated 90th and 95th percentile infusion rates from a national database for potential use as upper limit alarm settings. We extracted infusion rate data from 17 major hospitals using intraoperative records provided by Multicenter Perioperative Outcomes Group for adult surgery between 2008 and 2014. Seven infusions were selected for study: propofol, remifentanil, dexmedetomidine, norepinephrine, phenylephrine, nitroglycerin, and esmolol. Each dosage entry for an infusion during a procedure was included. We estimated the 50th, 90th, and 95th percentile levels for each infusion across institutions, and performed quantile regression to examine factors that might affect the percentiles rates, such as use in general anesthesia versus sedation. The median 90th and 95th percentile infusion rates (with interquartile range) for propofol were 150 (140-150) and 170 (150-200) μg/kg/min. Quantile regression demonstrated higher 90th and 95th percentile rates during sedation for gastrointestinal endoscopy than for all surgical procedures performed under general anesthesia. For selected vasoactive medications, the corresponding median 90th and 95th percentile rates (with interquartile range) were norepinephrine 14.0 (9.8-18.1) and 18.3 (12.6-23.9) μg/min, and phenylephrine 60 (55-80) and 80 (75-100) μg/min. Alarm settings based on infusion rate percentile limits would be triggered at predictable rates; ie, the 95th percentile would be exceeded and an alarm sounded during 1 in 20 infusion rate entries. As a result, institutions could establish pump alarm settings consistent with desired alarm frequency using their own or externally validated usage data. Further study will be needed to determine the optimal percentile for infusion alarm settings.

Spontaneously Assembled Nano-aggregates in Clear Green Tea Infusions from Camellia ptilophylla and Camellia sinensis.

PubMed

Lin, Xiaorong; Gao, Xiong; Chen, Zhongzheng; Zhang, Yuanyuan; Luo, Wei; Li, Xiaofei; Li, Bin

2017-05-10

Tea nano-aggregates spontaneously assembled in clear tea infusions are considered as the precursors of tea cream, although their molecular basis remains obscure. Here, we characterized nano-aggregates in green tea infusions from Camellia ptilophylla, a peculiar tea variety with 6.0% of theobromine, and Camellia sinensis as the control for comparative purpose. Numerous negatively charged spherical colloidal particles of 50-100 nm in diameter were primarily found in both green tea infusions. Catechins, proteins, and carbohydrates were confirmed as the dominant components in green tea nano-aggregates. In addition, iron, copper, nickel, proteins, and gallated catechins exhibited higher aggregating affinity than other components, whereas methylxanthines and calcium contributed to the transformation of nano-aggregates into tea cream. Green tea nano-aggregates were partly destroyed by simulated gastrointestinal digestion, and removing theses peculiar particles dramatically attenuated the bioaccessibility of methylxanthines, theanine, and some catechin monomers in green tea infusions. This study enhanced our knowledge of molecular interactions in the formation of green tea cream and provided insight into physicochemical profiles, phytochemical nature, and functional effects of green tea nano-aggregates.

Interference with the operation of medical devices resulting from the use of radio frequency identification technology.

PubMed

Houliston, Bryan; Parry, David; Webster, Craig S; Merry, Alan F

2009-06-19

To replicate electromagnetic interference (EMI) with a common drug infusion device resulting from the use of radio frequency identification (RFID) technology in a simulated operating theatre environment. An infusion pump, of a type previously reported as having failed due to RFID EMI, was placed in radio frequency (RF) fields of various strengths, and its operation observed. Different strength RF fields were created by varying the number of RFID readers, the use of a high-gain RFID antenna, the distance between the reader(s) and the infusion pump, and the presence of an RFID tag on the infusion pump. The infusion pump was not affected by low-power RFID readers, even when in direct contact. The pump was disrupted by a high-power reader at 10 cm distance when an RFID tag was attached, and by a combination of high-power and low-power readers at 10 cm distance. Electronic medical devices may fail in the presence of high-power RFID readers, especially if the device is tagged. However, low-power RFID readers appear to be safer.

Duration of Infusion Set Survival in Lipohypertrophy Versus Nonlipohypertrophied Tissue in Patients with Type 1 Diabetes

PubMed Central

Karlin, Andrew W.; Ly, Trang T.; Pyle, Laura; Forlenza, Gregory P.; Messer, Laurel; Wadwa, R. Paul; DeSalvo, Daniel J.; Payne, Sydney L.; Hanes, Sarah; Clinton, Paula; Buckingham, Bruce

2016-01-01

Abstract Background: Improved insulin infusion set survival and faster insulin action are important issues for pump users and for the development of an artificial pancreas. The current recommendation is to change infusion sets every 3 days. Our objectives were to determine the effect of lipohypertrophy (LH) on infusion set survival and continuous glucose monitoring glucose levels. Research Design and Methods: In this multicenter crossover trial, we recruited 20 subjects (age 28.1 ± 9.0 years) with type 1 diabetes (duration 17.5 ± 8.8 years) and an area of lipohypertrophied tissue >3 cm. Subjects alternated weekly wearing a Teflon infusion set in an area of either LH or non-LH for 4 weeks. Sets were changed after (a) failure or (b) surviving 7 days of use. Results: The least-squares mean duration of infusion set survival for sets that lasted <7 days in lipohypertrophied tissue was 4.31 days compared with 4.12 days in nonlipohypertrophied tissue (P = 0.71). The average duration of set survival for individual subjects ranged from 2.2 to 7.0 days. Infusion sets in lipohypertrophied tissue failed due to hyperglycemia in 35% of subjects compared with 23% in nonlipohypertrophied tissue (P = 0.22). Both lipohypertrophied and nonlipohypertrophied tissues displayed a general increase in mean daily glucose after the third day of infusion set wear, but daily mean glucose did not differ by tissue type (P > 0.38 on each day). Conclusion: LH did not significantly affect infusion set survival or mean glucose. Achieving optimal infusion set performance requires research into factors affecting set survival. Additionally, the recommendation for duration of set change may need to be individualized. PMID:27227290

Analysis of a simulation algorithm for direct brain drug delivery

PubMed Central

Rosenbluth, Kathryn Hammond; Eschermann, Jan Felix; Mittermeyer, Gabriele; Thomson, Rowena; Mittermeyer, Stephan; Bankiewicz, Krystof S.

2011-01-01

Convection enhanced delivery (CED) achieves targeted delivery of drugs with a pressure-driven infusion through a cannula placed stereotactically in the brain. This technique bypasses the blood brain barrier and gives precise distributions of drugs, minimizing off-target effects of compounds such as viral vectors for gene therapy or toxic chemotherapy agents. The exact distribution is affected by the cannula positioning, flow rate and underlying tissue structure. This study presents an analysis of a simulation algorithm for predicting the distribution using baseline MRI images acquired prior to inserting the cannula. The MRI images included diffusion tensor imaging (DTI) to estimate the tissue properties. The algorithm was adapted for the devices and protocols identified for upcoming trials and validated with direct MRI visualization of Gadolinium in 20 infusions in non-human primates. We found strong agreement between the size and location of the simulated and gadolinium volumes, demonstrating the clinical utility of this surgical planning algorithm. PMID:21945468

Infusion System Architecture Impacts the Ability of Intensive Care Nurses to Maintain Hemodynamic Stability in a Living Swine Simulator.

PubMed

Pezone, Matthew J; Peterfreund, Robert A; Maslov, Mikhail Y; Govindaswamy, Radhika R; Lovich, Mark A

2016-05-01

The authors have previously shown that drug infusion systems with large common volumes exhibit long delays in reaching steady-state drug delivery and pharmacodynamic effects compared with smaller common-volume systems. The authors hypothesized that such delays can impede the pharmacologic restoration of hemodynamic stability. The authors created a living swine simulator of hemodynamic instability in which occlusion balloons in the aorta and inferior vena cava (IVC) were used to manipulate blood pressure. Experienced intensive care unit nurses blinded to the use of small or large common-volume infusion systems were instructed to maintain mean arterial blood pressure between 70 and 90 mmHg using only sodium nitroprusside and norepinephrine infusions. Four conditions (IVC or aortic occlusions and small or large common volume) were tested 12 times in eight animals. After aortic occlusion, the time to restore mean arterial pressure to range (t1: 2.4 ± 1.4 vs. 5.0 ± 2.3 min, P = 0.003, average ± SD), time-out-of-range (tOR: 6.2 ± 3.5 vs. 9.5 ± 3.4 min, P = 0.028), and area-out-of-range (pressure-time integral: 84 ± 47 vs. 170 ± 100 mmHg · min, P = 0.018) were all lower with smaller common volumes. After IVC occlusion, t1 (3.7 ± 2.2 vs. 7.1 ± 2.6 min, P = 0.002), tOR (6.3 ± 3.5 vs. 11 ± 3.0 min, P = 0.007), and area-out-of-range (110 ± 93 vs. 270 ± 140 mmHg · min, P = 0.003) were all lower with smaller common volumes. Common-volume size did not impact the total amount infused of either drug. Nurses did not respond as effectively to hemodynamic instability when drugs flowed through large common-volume infusion systems. These findings suggest that drug infusion system common volume may have clinical impact, should be minimized to the greatest extent possible, and warrants clinical investigations.

[Intraosseous infusion. An important technique also for paediatric anaesthesia].

PubMed

Weiss, M; Henze, G; Eich, C; Neuhaus, D

2009-09-01

Timely establishment of venous access in infants and toddlers can prove a particularly challenging task. Since the 1940s the technique of intraosseous infusion has established itself as a valuable alternative means for rapid, efficient and safe delivery of drugs and fluids to critically ill children. Whereas international guidelines for paediatric emergency medical care have assigned intraosseous infusion a high priority, most anaesthetists utilize this well-proven technique with great reluctance. This article describes the technique of intraosseous infusion, introduces two different cannulation systems, and discusses its potential indications in paediatric anaesthesia, based on current emergency medical care guidelines as well as some of our own case studies. In particular, children with acutely life-threatening conditions, such as circulatory arrest, laryngospasm, acute airway haemorrhage, hypovolaemic shock or hypothermia secondary to extensive burns, should receive an intraosseous cannula if intravenous access cannot be rapidly established. Future discussion may reveal whether a transiently inserted intraosseous infusion would also be indicated if the child with difficult or impossible venous access presents without acute life-threatening conditions for anaesthesia. Successful application of the intraosseous infusion technique requires immediate access to the necessary equipment, intensive education, continuous training and clear guidelines for its application in an anaesthesia department.

The effects of programmed administration of human parathyroid hormone fragment (1-34) on bone histomorphometry and serum chemistry in rats

NASA Technical Reports Server (NTRS)

Dobnig, H.; Turner, R. T.

1997-01-01

PTH treatment can result in dramatic increases in cancellous bone volume in normal and osteopenic rats. However, this potentially beneficial response is only observed after pulsatile treatment; continuous infusion of PTH leads to hypercalcemia and bone abnormalities. The purpose of these studies was to determine the optimal duration of the PTH pulses. A preliminary study revealed that human PTH-(1-34) (hPTH) is cleared from circulation within 6 h after sc administration of an anabolic dose of the hormone (80 microg/kg). To establish the effects of gradually extending the duration of exposure to hPTH without increasing the daily dose, we programmed implanted Alzet osmotic pumps to deliver the 80 microg/kg x day dose of the hormone during pulses of 1, 2, and 6 h/day, or 40 microg/kg x day continuously. Discontinuous infusion was accomplished by alternate spacing of external tubing with hPTH solution and sesame oil. After 6 days of treatment, we evaluated serum chemistry and bone histomorphometry. As negative and positive controls, groups of rats received pumps that delivered vehicle only and 80 microg/kg x day hPTH by daily sc injection, respectively. Dynamic and static bone histomorphometry revealed that the daily sc injection and 1 h/day infusion dramatically increased osteoblast number and bone formation in the proximal tibial metaphysis, whereas longer infusion resulted in systemic side-effects, including up to a 10% loss in body weight, hypercalcemia, and histological changes in the proximal tibia resembling abnormalities observed in patients with chronic primary hyperparathyroidism, including peritrabecular marrow fibrosis and focal bone resorption. Infusion for as little as 2 h/day resulted in minor weight loss and changes in bone histology that were intermediate between sc and continuous administration. The results demonstrate that the therapeutic interval for hPTH exposure is brief, but that programmed administration of implanted hormone is a feasible alternative to daily injection as a route for administration of the hormone.

Corrosion Behaviour in Human Stimulation Media of a High Entropy Titan-Based Alloy

NASA Astrophysics Data System (ADS)

Ghiban, B.; Popescu, G.; Lazar, C.; Rosu, L.; Constantin, I.; Olaru, M.; Carlan, B.

2018-06-01

The paper presents results on the corrosion behavior of high entropy alloys, commonly called BIOHEA in human physiological simulating media, respectively in the NaCl infusion solution and Ringer’s lactate infusion solution. Corrosion tests were performed by potendiodinamic test using AUTOLAB type potentiostat equipped with specialized corrosion software including the PGSTAT302N, BA and SCAN250 modules. Three entropy alloy systems were investigated: FeTa0.5Nb0.5Ti1.5Zr0.5 (BIOHEA 1), FeMnNb0.5TiZr0.5 (BIOHEA 3), FeTa0.5Nb0.5TiZr0.5 (BIOHEA 4), and BIOHEA alloy 2 was obtained by remelting BIOHEA 1. A comparison of the results obtained in the present tests and the data from the literature shows, on the one hand, that the global results can be compared with the different results from the literature, and, on the other hand, the results are new, in the sense that in any work there are no combinations of alloys studied here or human simulating medians used for testing. The conclusion of the experimental investigations in the present paper is the fact that regardless of the simulation test environment, all the alloys experimental alloys have similar behaviors, there is a difference between the chemical composition of the experimental alloy and the displacement of the corrosion potential values at electropositive values, decreasing of corrosion current, and corrosion rates. The experimental results allow the corrosion resistance of the investigated alloys, alloy BIOHEA 2 having the best corrosion behavior in both test media, with very low corrosion rates (respectivelly 0.067 μm/year in NaCl infusion solution, and 0.021 μm / year in Ringer’s lactate infusion solution).

Ketamine infusions for treatment resistant depression: a series of 28 patients treated weekly or twice weekly in an ECT clinic.

PubMed

Diamond, Peter R; Farmery, Andrew D; Atkinson, Stephanie; Haldar, Jag; Williams, Nicola; Cowen, Phil J; Geddes, John R; McShane, Rupert

2014-06-01

Ketamine has a rapid antidepressant effect in treatment-resistant depression (TRD). The effects on cognitive function of multiple ketamine infusions and of concurrent antidepressant medication on response rate and duration are not known. Twenty-eight patients with uni- or bipolar TRD were treated over three weeks with either three or six ketamine infusions (0.5 mg/kg over 40 minutes) in the recovery room of a routine ECT clinic. Post-treatment memory assessments were conducted on day 21 (4-7 days after the final infusion). Patients were followed up for six months where possible, with severity of depression and side effects monitored throughout. Eight (29%) patients responded of whom four remitted. Only three (11%) patients had responded within six hours after a single infusion, but in all responders, the response had developed before the third infusion. The duration of response from the final infusion was variable (median 70, range 25-168 days). Discontinuations included two (7%) because of acute adverse reactions during the infusion and five (18%) because of failure to benefit and increasing anxiety. Ketamine was not associated with memory impairment. The ECT clinic was rated suitable by patients and offered appropriate levels of monitoring. This small, open label naturalistic study shows that up to six low dose ketamine infusions can safely be given within an existing NHS clinical structure to patients who continue their antidepressants. The response rate was comparable to that found in RCTs of single doses of ketamine in antidepressant-free patients but took slightly longer to develop. © The Author(s) 2014.

Randomized trial of subfascial infusion of ropivacaine for early recovery in laparoscopic colorectal cancer surgery

PubMed Central

Lee, Sang Hyun; Kim, Go Eun; Kim, Hee Cheol; Jun, Joo Hyun; Lee, Jin Young; Shin, Byung-Seop; Yoo, Heejin; Jung, Sin-Ho; Kim, Joungyoun; Lee, Seung Hyeon; Yo, Deok Kyu; Na, Yu Ri

2016-01-01

Background There is a need for investigating the analgesic method as part of early recovery after surgery tailored for laparoscopic colorectal cancer (LCRC) surgery. In this randomized trial, we aimed to investigate the analgesic efficacy of an inverse ‘v’ shaped bilateral, subfascial ropivacaine continuous infusion in LCRC surgery. Methods Forty two patients undergoing elective LCRC surgery were randomly allocated to one of two groups to receive either 0.5% ropivacaine continuous infusion at the subfascial plane (n = 20, R group) or fentanyl intravenous patient controlled analgesia (IV PCA) (n = 22, F group) for postoperative 72 hours. The primary endpoint was the visual analogue scores (VAS) when coughing at postoperative 24 hours. Secondary end points were the VAS at 1, 6, 48, and 72 hours, time to first flatus, time to first rescue meperidine requirement, rescue meperidine consumption, length of hospital stay, postoperative nausea and vomiting, sedation, hypotension, dizziness, headache, and wound complications. Results The VAS at rest and when coughing were similar between the groups throughout the study. The time to first gas passage and time to first rescue meperidine at ward were significantly shorter in the R group compared to the F group (P = 0.010). Rescue meperidine was administered less in the R group; however, without statistical significance. Other study parameters were not different between the groups. Conclusions Ropivacaine continuous infusion with an inverse ‘v ’ shaped bilateral, subfascial catheter placement showed significantly enhanced bowel recovery and analgesic efficacy was not different from IV PCA in LCRC surgery. PMID:27924202

Knee strength retention and analgesia with continuous perineural fentanyl infusion after total knee replacement: randomized controlled trial.

PubMed

Mangar, Devanand; Karlnoski, Rachel A; Sprenker, Collin J; Downes, Katheryne L; Taffe, Narrene; Wainwright, Robert; Gustke, Kenneth; Bernasek, Thomas L; Camporesi, Enrico

2014-04-01

Despite providing adequate pain relief, a femoral nerve block can induce postoperative muscle weakness after total knee arthoplasty (TKA). Fentanyl has been shown to have peripheral effects but has not been used as a perineural infusate alone after TKA. Sixty patients scheduled for TKA were randomized to one of three blinded groups: a continuous 24 h infusion of either fentanyl 3 μg/ml, ropivacaine 0.1%, or 0.9% normal saline through a femoral nerve sheath catheter at 10 ml/h. The main outcome was maximum voluntary isometric contraction (MVIC) in the quadriceps femoris (knee extension), measured by a handheld dynamometer (Nm/kg). Other variables assessed were preoperative and postoperative visual analog scale (VAS) scores, hamstrings MVIC (knee flexion), active range of motion of the operative knee, distance ambulated, incidence of knee buckling, supplemental morphine usage, postoperative side effects, and serum fentanyl levels. Quadriceps MVIC values were significantly greater in the fentanyl group compared to the group that received ropivacaine (median values, 0.08 vs. 0.03 Nm/kg; p = 0.028). The incidence of postoperative knee buckling upon ambulation was higher in the ropivacaine group compared to the fentanyl group, although not statistically significant (40% vs. 15 %, respectively; p = 0.077). VAS scores while ambulating were not significantly different between the fentanyl group and the ropivacaine group (p = 0.270). Postoperative morphine consumption, nausea and vomiting, and resting VAS scores were similar among the three groups. A continuous perineural infusion of fentanyl produced greater strength retention than ropivacaine post-TKA.

Using UV-Vis spectroscopy for simultaneous geographical and varietal classification of tea infusions simulating a home-made tea cup.

PubMed

Diniz, Paulo Henrique Gonçalves Dias; Barbosa, Mayara Ferreira; de Melo Milanez, Karla Danielle Tavares; Pistonesi, Marcelo Fabián; de Araújo, Mário César Ugulino

2016-02-01

In this work we proposed a method to verify the differentiating characteristics of simple tea infusions prepared in boiling water alone (simulating a home-made tea cup), which represents the final product as ingested by the consumers. For this purpose we used UV-Vis spectroscopy and variable selection through the Successive Projections Algorithm associated with Linear Discriminant Analysis (SPA-LDA) for simultaneous classification of the teas according to their variety and geographic origin. For comparison, KNN, CART, SIMCA, PLS-DA and PCA-LDA were also used. SPA-LDA and PCA-LDA provided significantly better results for tea classification of the five studied classes (Argentinean green tea; Brazilian green tea; Argentinean black tea; Brazilian black tea; and Sri Lankan black tea). The proposed methodology provides a simpler, faster and more affordable classification of simple tea infusions, and can be used as an alternative approach to traditional tea quality evaluation as made by skilful tasters, which is evidently partial and cannot assess geographic origins. Copyright © 2015 Elsevier Ltd. All rights reserved.

Colorimetric device for measurement of transvascular fluid flux in blood-perfused organs.

PubMed

Oppenheimer, L; Richardson, W N; Bilan, D; Hoppensack, M

1987-01-01

The aim of this study was to develop a device capable of measuring transvascular fluid flux in blood-perfused organs. For any given blood flow through the organ (QT), transvascular flux (QF) can be considered as the fraction of QT exchange. Presumably, QF would change the background concentration of an impermeable tracer residing in the perfusate. Thus QF could be calculated from the relative changes in tracer concentration for any given QT. We have used Blue Dextran (1 g/l of blood) as the reference tracer. Because the minimum molecular weight of Blue Dextran is 2 X 10(6), we anticipated it to behave as an impermeable tracer in most organs. QF was simulated with continuous infusions of plasma, normal saline solution, and a 50% mixture of both. Changes in Blue Dextran concentration were continuously followed colorimetrically by changes in transmission of specific light at a wavelength of 632 nm. Because 632-nm light is affected by hematocrit and O2 saturation changes, two additional wavelengths were used: 815-nm, which is not affected by saturation or Blue Dextran concentration changes, was used to account for changes in hematocrit, and 887-nm specific light, which is not affected by Blue Dextran, served to correct for saturation changes. Red cells could not be used as the reference tracer because of the possibility of hematocrit changes independent of fluid flux (Fahraeus effect). The device so constructed proved capable of measuring rates of fluid infusion in the order of 0.1% of QT with a variability of 10% around the mean.

Semi-mechanistic autoinduction model of midazolam in critically ill patients: population pharmacokinetic analysis.

PubMed

Aoyama, T; Hirata, K; Yamamoto, Y; Yokota, H; Hayashi, H; Aoyama, Y; Matsumoto, Y

2016-08-01

Midazolam (MDZ) is commonly used for sedating critically ill patients. The daily dose required for adequate sedation increases in increments over 100 h after administration. The objectives of this study were to characterize the MDZ pharmacokinetics in critically ill patients and to describe the phenomenon of increasing daily dose by means of population pharmacokinetic analysis. Data were obtained from 30 patients treated in an intensive care unit. The patients received MDZ intravenously as a combination of bolus and continuous infusion. Serum MDZ concentration was assayed by high-performance liquid chromatography. Population pharmacokinetic analysis was performed using the NONMEM software package. The alteration of clearance unexplained by demographic factors and clinical laboratory data was described as an autoinduction of MDZ clearance using a semi-mechanistic pharmacokinetic-enzyme turnover model. The final population pharmacokinetic model was a one-compartment model estimated by incorporating a semi-mechanistic pharmacokinetic-enzyme turnover model for clearance, taking autoinduction into account. A significant covariate for MDZ clearance was total bilirubin. An increase in total bilirubin indicated a reduction in MDZ clearance. From simulation using the population pharmacokinetic parameters obtained in this study, MDZ clearance increased 2·3 times compared with pre-induced clearance 100 h after the start of 12·5 mg/h continuous infusion. Autoinduction and total bilirubin were significant predictors of the clearance of MDZ in this population. Step-by-step dosage adjustment using this population pharmacokinetic model may be useful for establishing a MDZ dosage regimen in critically ill patients. © 2016 John Wiley & Sons Ltd.

A randomized comparison of ropivacaine 0.1% and 0.2% for continuous interscalene block after shoulder surgery.

PubMed

Yang, Chun Woo; Jung, Sung Mee; Kang, Po Soon; Kwon, Hee Uk; Cho, Choon Kyu; Lee, Younsuk; Kim, Chul Woung; Kim, Su Young

2013-03-01

The optimal concentration of ropivacaine for continuous interscalene block after shoulder surgery is currently unknown. Fifty-six patients received a perineural infusion of either ropivacaine 0.1% or 0.2% for 48 hours after shoulder surgery. We assessed pain scores as primary end points and supplemental analgesia, ropivacaine consumption, motor block, side effects, and patient satisfaction as secondary end points. Pain scores were not statistically different during the infusion periods; however, supplemental analgesia consumption was higher in the group receiving ropivacaine 0.1% during the first 24 hours (64% vs 28%, P = 0.022). Other secondary end points were statistically inconclusive. These results suggest that ropivacaine 0.2% provides more effective analgesia than ropivacaine 0.1% during the first 24 hours for continuous interscalene block after shoulder surgery.

Chloral hydrate enteral infusion for sedation in ventilated children: the CHOSEN pilot study.

PubMed

Joffe, Ari R; Hogan, Jessica; Sheppard, Cathy; Tawfik, Gerda; Duff, Jonathan P; Garcia Guerra, Gonzalo

2017-11-26

We aimed to test a novel method of delivery of chloral hydrate (CH) sedation in ventilated critically ill young children. Children < 12 years old, within 72 hours of admission, who were ventilated, receiving enteral tube-feeds, with intermittent CH ordered were enrolled after signed consent. Patients received a CH loading-dose of 10 mg/kg enterally, then a syringe-pump enteral infusion at 5 mg/kg/hour, increasing to a maximum of 9 mg/kg/hour. Cases were compared to historical controls matched for age group and Pediatric Risk of Mortality score (PRISM) category, using Fisher's exact test and the t test. The primary outcome was feasibility, defined as the use of an enteral CH continuous infusion without discontinuation attributable to a pre-specified potential harm. There were 21 patients enrolled, at age 11.4 (12.1) months, with bronchiolitis in 10 (48%), a mean Pediatric Logistic Organ Dysfunction (PELOD) score of 6.2 (5.2), and having received enteral CH continuous infusion for 4.5 (2.2) days. Infusion of CH was feasible in 20/21 (95%; 95% CI 76-99%) patients, with one (5%) adverse event of duodenal ulcer perforation on day 3 in a patient with croup receiving regular ibuprofen and dexamethasone. The CH infusion dose (mg/kg/h) on day 2 (n = 20) was 8.9 (IQR 5.9, 9), and on day 4 (n = 11) was 8.8 (IQR 7, 9). Days to titration of adequate sedation (defined as ≤ 3 PRN doses/shift) was 1 (IQR 0.5, 2.5), and hours to awakening for extubation was 5 (IQR 2, 9). Cases (versus controls) had less positive fluid balance at 48 h (-2 (45) vs. 26 (46) ml/kg, p = 0.051), and a decrease in number of PRN sedation doses from 12 h pre to 12 hours post starting CH (4.7 (3.3) to 2.6 (2.8), p = 0.009 versus 2.9 (3.9) to 3.4 (5), p = 0.74). There were no statistically significant differences between cases and controls in inotrope scores, signs or treatment of withdrawal, or PICU days. Delivering CH by continuous enteral infusion is feasible, effective, and may be associated with less positive fluid balance. Whether there is a risk of duodenal perforation requires further study.

Kiovig for primary immunodeficiency: reduced infusion and decreased costs per infusion.

PubMed

Connolly, Mark; Simoens, Steven

2011-09-01

Kiovig is a ready-to-use 10% liquid immunoglobulin preparation that is medically indicated for the treatment of primary immunodeficiency. This study aims to conduct an economic evaluation which compares the intravenous immunoglobulin (IVIg) preparations Kiovig, Multigam, and Sandoglobulin from the Belgian societal perspective. As three prospective studies have observed no difference in outcomes, a cost-minimization analysis is considered appropriate to evaluate differences in treatment costs that can arise from IVIgs. A decision-analytic model simulated treatment costs attributed to one infusion. Resource use data were derived from a Dutch costing study. Cost items included immunoglobulin costs, pharmacy administration and nursing costs, mini-forfait for hospital infusion, costs of adverse events, and lost productivity with 2009 as base year. Cost data were identified from published sources and Belgian hospital administrators. A probabilistic sensitivity analysis explored the impact of parameter uncertainty on cost results. Costs per infusion cycle in adult primary immunodeficiency patients were €1,046 (95% confidence interval: €1,006-1,093) with Kiovig; €1,102 (€1,064-1,147) with Multigam; and €1,147 (€1,108-1,193) with Sandoglobulin. The average cost savings per infusion with Kiovig as compared to Multigam and Sandoglobulin amounted to €56 and €101 per infusion. In conclusion, treatment costs with Kiovig were shown to be lower as compared to other IVIgs in Belgium. Reduced costs per infusion were attributed to lower costs associated with treating adverse events and the opportunity cost of nursing time and time off work for working adults. Copyright © 2011 Elsevier B.V. All rights reserved.

Psychiatric side effects of ketamine in hospitalized medical patients administered subanesthetic doses for pain control.

PubMed

Rasmussen, Keith G

2014-08-01

To assess the psychiatric side effects of ketamine when administered in subanesthetic doses to hospitalized patients. It is hypothesized that such effects occur frequently. In this retrospective study, the medical records of 50 patients hospitalized on medical and surgical units at our facility who had continuous intravenous infusions of ketamine for pain or mild sedation were reviewed. Patient progress in the days following the start of ketamine infusion was reviewed and response to ketamine was noted. Twenty-two percent of the patients were noted to have some type of psychiatric reaction to ketamine, including agitation, confusion, and hallucinations. These reactions were relatively short lived, namely, occurring during or shortly after the infusions. No association was found between patient response to ketamine and gender, age, or infusion rate. Awareness of the psychiatric side effects of ketamine is an important consideration for clinicians administering this medication either for pain control or for depressive illness.

Seizure and electroencephalographic changes in the newborn period induced by opiates and corrected by naloxone infusion.

PubMed

da Silva, O; Alexandrou, D; Knoppert, D; Young, G B

1999-03-01

To describe the association between opioid administration in the newborn period and neurologic abnormalities. Case reports of two infants who presented with seizure activity and abnormal electroencephalograms associated with opiate administration, and reversed by naloxone. The first was a preterm infant who developed a burst-suppression pattern on the electroencephalogram while receiving a continuous infusion of morphine and muscle paralysis. Naloxone injection during the electroencephalogram recording reversed the burst-suppression pattern. The second was a term infant receiving fentanyl infusion for pain control following surgery, who presented with motor seizure that was only partially controlled with barbiturates. An abnormal electroencephalogram recording during the opiate infusion improved with naloxone administration. Our observations indicate a potential for neurologic abnormalities, including induction of seizure activity and electroencephalogram abnormalities, suggesting caution when opiates are used for sedation and/or pain control in the newborn period.

Analgesic plasma concentrations of morphine in children with terminal malignancy receiving a continuous subcutaneous infusion of morphine sulfate to control severe pain.

PubMed

Nahata, M C; Miser, A W; Miser, J S; Reuning, R H

1984-02-01

Three children with terminal malignancy received a continuous subcutaneous infusion of morphine sulfate for the control of severe pain, the morphine dose being adjusted until the patient and/or parent reported complete freedom from pain. Analgesic plasma morphine concentrations at the steady state in these patients ranged from 12.9 to 57 ng/ml (median 19.6 ng/ml) while receiving morphine doses of 0.45-2.0 mg/h (0.034-0.06 mg/kg/h). One patient, who received 2 mg morphine per hour for 12 days demonstrated a 2-fold variation in steady-state plasma concentration during this period.

Continuous subcutaneous infusion of ketorolac in cancer neuropathic pain unresponsive to opioid and adjuvant drugs. A case report.

PubMed

Ripamonti, C; Ticozzi, C; Zecca, E; Rodriguez, C H; De Conno, F

1996-01-01

Ketorolac is a new non-steroidal anti-inflammatory drug (NSAID) having a potent nonopioid analgesic activity. Administered by continuous subcutaneous infusion (CSI), its analgesic efficacy has been documented in the treatment of somatic and visceral cancer pain whilst it has been shown to be ineffective in the treatment of neuropathic pain. Here is a description of a cancer patient with neuropathic pain unresponsive to anticonvulsant or antidepressant drugs administered in association or not with oral opioids but who was successfully treated with ketorolac alone via CSI. Furthermore, the analgesia lasted over 75 days of treatment without any significant renal and gastric side effects.

Continuous infusion of recombinant activated factor VII for bleeding control after lobectomy in a patient with inherited factor VII deficiency.

PubMed

Miyata, Naoko; Isaka, Mitsuhiro; Kojima, Hideaki; Maniwa, Tomohiro; Takahashi, Shoji; Takamiya, Osamu; Ohde, Yasuhisa

2016-03-01

Inherited factor VII (FVII) deficiency is a rare recessive inherited coagulation disorder with limited available information, especially in patients undergoing major thoracic surgery. In addition, an optimal management strategy for the disease has not been defined. We herein report a case involving a 61-year-old man with asymptomatic FVII deficiency who underwent a right middle and lower lobectomy to treat lung cancer. To the best of our knowledge, the present report is the first to describe the use of recombinant activated FVII continuous infusion for bleeding control after a major thoracic surgery in a patient with inherited FVII deficiency.

[The use of continuous subcutaneous insulin infusion (CSII) with personal insulin pumps in the treatment of children and adolescents with diabetes type 1].

PubMed

Jarosz-Chobot, Przemysława

2004-01-01

This paper sums up recently published researches on the continuous subcutaneous insulin infusion (CSII) with the use of insulin pump in children and adolescents with diabetes type 1. Obtaining a balance in the organism metabolism in childhood and adolescence diabetology is nowadays one of the most important rules of the diabetes management in children. One of the modern ways to achieve that goal is the intensive insulin therapy model with use of the insulin pump. In this paper the advantages and disadvantages as well as the indications and contraindications for the CSII in children and adolescents with diabetes are widely discussed.

Relationships between antimicrobial effect and area under the concentration-time curve as a basis for comparison of modes of antibiotic administration: meropenem bolus injections versus continuous infusions.

PubMed Central

Firsov, A A; Mattie, H

1997-01-01

In comparative studies of different modes of administration (MAs) simulated in in vitro dynamic models, only one dose of antibiotic is usually mimicked. Such an experimental design can provide a prediction of the antimicrobial effect (AME) of a given combination of drug, clinical isolate, and infection site, but may be inappropriate for accurate comparison of MAs. An alternative design providing comparison of different MAs with various antibiotic doses in a wide range and with evaluation of the respective relationships between AME and the AUC was proposed and examined. Two series of meropenem pharmacokinetic profiles, i.e., monoexponentially decreasing concentrations (bolus doses) and constant concentrations (6-h continuous infusion), were in vitro simulated. The simulated initial concentrations (Co[from 0.62 to 48 micrograms/ml]) and steady-state concentrations (Css[from 0.016 to 8 micrograms/ml]) were chosen to provide similar AUC for 0 to 6 h (AUC0-6) ranges for both MAs (from 0.070 to 50.0 micrograms.h/ml and from 0.09 to 48.0 micrograms.h/ml, respectively). The AME of meropenem on Staphylococcus aureus ATCC 25923 (MIC, 0.06 micrograms/ml) was determined at each time (t) point as a difference (E) between the logarithms of viable counts (N) in the control cultures without antibiotic (NC) and in cultures exposed to antibiotics (NA). Time courses of E observed at different Co of Css levels were compared in terms of the areas under the E-t curves (ABBCt). The finite values of the ABBCt observed by the end of the 6 -h observation period, which are equivalent to the area between bacterial count-time curves observed in the absence and presence of antibiotic (ABBC), were plotted versus the respective AUCs produced by each of the MAs. The ABBC versus AUC curves had a similar pattern: a plateau achieved at high AUCs followed by a steep rise in ABBC at relatively low AUCs was inherent in both of the MAs. The superiority of bolus dosing over the infusions could be documented only for meropenem concentrations below the MIC. At higher Co or Css (i.e., at an AUC of > or = 0.4 micrograms.h/ml), the ABBC versus AUC curves plotted for each of the MAs could practically be superimposed. On the whole, both MAs appeared to be equiefficient in terms of the ABBC. These results suggest that AUC analysis of the AME may be a useful tool for comparing different MAs. Such comparative studies should be designed in a manner that provides the use of similar AUC ranges, since the AUC may be considered as a common pharmacokinetic denominator in comparing one MA or dosing regimen to another. PMID:9021191

The calcitonin gene-related peptide receptor antagonist MK-8825 decreases spinal trigeminal activity during nitroglycerin infusion

PubMed Central

2013-01-01

Background Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are regarded as key mediators in migraine and other primary headaches. Migraineurs respond to infusion of nitroglycerin with delayed headaches, and inhibition of CGRP receptors has been shown to be effective in migraine therapy. In animal experiments nitrovasodilators like nitroglycerin induced increases in spinal trigeminal activity, which were reversed after inhibition of CGRP receptors. In the present study we asked if CGRP receptor inhibition can also prevent spinal trigeminal activity induced by nitroglycerin. Methods In isoflurane anaesthetised rats extracellular recordings were made from neurons in the spinal trigeminal nucleus with meningeal afferent input. The non-peptide CGRP receptor inhibitor MK-8825 (5 mg/kg) dissolved in acidic saline (pH 3.3) was slowly infused into rats one hour prior to prolonged glyceryl trinitrate (nitroglycerin) infusion (250 μg/kg/h for two hours). Results After infusion of MK-8825 the activity of spinal trigeminal neurons with meningeal afferent input did not increase under continuous nitroglycerin infusion but decreased two hours later below baseline. In contrast, vehicle infusion followed by nitroglycerin was accompanied by a transient increase in activity. Conclusions CGRP receptors may be important in an early phase of nitroglycerin-induced central trigeminal activity. This finding may be relevant for nitroglycerin-induced headaches. PMID:24256609

Effect of repeated injection and continuous infusion of omeprazole and ranitidine on intragastric pH over 72 hours.

PubMed

Netzer, P; Gaia, C; Sandoz, M; Huluk, T; Gut, A; Halter, F; Hüsler, J; Inauen, W

1999-02-01

In healthy subjects and patients with bleeding peptic ulcers, ranitidine and omeprazole, given parenterally, achieve high intragastric pH values on the first day of therapy. However, data on the antisecretory effect beyond the first 24 h is scanty. In addition, the superiority of either infusion or injection of omeprazole remains unproven. Thus, we have compared the antisecretory effect of high dose omeprazole and ranitidine infusion and injection over the critical first 72 h. A total of 34 healthy volunteers were randomized into a double-blind crossover 72 h intragastric pH-metry study (data compared: median pH, percentage of time with pH >4 and pH >6). Omeprazole-infusion: initial bolus of 80 mg + 8 mg/h; omeprazole-injection: initial bolus of 80 mg + 40 mg/6 h; Ranitidine-infusion: initial bolus of 50 mg + 0.25 mg/kg/h; ranitidine-injection: 100 mg/6 h. Omeprazole-infusion versus ranitidine-infusion: on day 1: median pH 6.1 vs 5.1 (p = 0.01) and 95% vs 70% was pH >4 (p < 0.01); on day 2: median pH 6.2 vs 3.2 (p < 0.01); and 100% vs 38% was pH >4 (p < 0.01); on day 3: median pH 6.3 vs 2.7 (p < 0.01); 100% vs 26% was pH >4 (p < 0.01). Injections of both drugs were significantly less effective than the infusions on day 1. Thereafter, omeprazole injection was almost as effective as omeprazole infusion, whereas ranitidine injection and infusion were equally effective. Our study shows, for the first time, that omeprazole infusion was significantly superior to all other regimens by having a high median pH >6 on each day. The tolerance effect of ranitidine, however, led to a rapid loss of antisecretory activity on days 2 and 3, rendering it inappropriate for situations in which high intragastric pH-levels appear to be essential.

Cardiac Arrhythmia and Injury Induced in Rats by Burst and Pulsed Mode Ultrasound with Gas Body Contrast Agent

PubMed Central

Miller, Douglas L.; Dou, Chunyan; Lucchesi, Benedict R.

2009-01-01

Objective Premature complexes (PCs) in the electrocardiogram (ECG) signal have been reported for myocardial contrast echocardiography and also for burst mode (physical therapy) ultrasound with gas body contrast agent at lower peak rarefactional pressure amplitudes (PRPAs). For contrast echocardiography, irreversibly injured cardiomyocytes have been associated with the arrhythmia. The objective was to determine if cardiomyocyte injury is associated with the PCs induced by the burst mode at lower PRPAs. Methods Anesthetized rats were exposed to focused 1.5 MHz ultrasound in a water bath. Evans blue dye was injected IP to stain injured cardiomyocytes and Definity ultrasound contrast agent was infused IV. Continuous burst mode simulated physical therapy ultrasound. Intermittent 2 ms bursts, or envelopes of pulses simulating diagnostic ultrasound, were triggered 1:4 at end systole. PCs were observed on ECG recordings and stained cardiomyocytes were counted in frozen sections. Results The continuous burst mode produced variable PCs and stained cells above 0.3 MPa PRPA. The triggered bursts above 0.3 MPa and pulse envelopes above 1.2 MPa produced statistically significant (P<0.01) PCs and stained cardiomyocytes. Conclusion Irreversible cardiomyocyte injury was associated with the development of PCs for burst mode and occurred at substantially lower PRPAs than for pulsed ultrasound. PMID:19854967

Effects of 2 different medetomidine infusion rates on selected neurohormonal and metabolic parameters in dogs

PubMed Central

Lamont, Leigh; Burton, Shelley; Caines, Deanne; Masaoud, Elmabrok; Troncy, Eric

2012-01-01

The effects of 2 different 8-hour continuous rate infusions (CRIs) of medetomidine on epinephrine, norepinephrine, cortisol, glucose, and insulin levels were investigated in 6 healthy dogs. Each dog received both treatments and a control as follows: MED1 = 2 μg/kg bodyweight (BW) loading dose followed by 1 μg/kg BW per hour CRI; MED2 = 4 μg/kg BW loading dose followed by 2 μg/kg BW per hour CRI; and CONTROL = saline bolus followed by a saline CRI. Both infusion rates of medetomidine decreased norepinephrine levels throughout the infusion compared to CONTROL. While norepinephrine levels tended to be lower with the MED2 treatment compared to the MED1, this difference was not significant. No differences in epinephrine, cortisol, glucose, or insulin were documented among any of the treatments at any time point. At the low doses used in this study, both CRIs of medetomidine decreased norepinephrine levels over the 8-hour infusion period, while no effects were observed on epinephrine, cortisol, glucose, and insulin. PMID:23024457

Baroreflex Sensitivity Decreases During 90-Day Bed Rest

NASA Technical Reports Server (NTRS)

Stenger, M. B.; Arzeno, N. M.; Platts, S. H.

2008-01-01

Baroreflex sensitivity (BRS) decreases during spaceflight and simulated spaceflight (head down bed rest [BR]). However, previous studies have only examined BRS in response to a limited blood pressure (BP) range or to a single sudden change in BP. PURPOSE: The purpose of this study was to examine BRS during 90 days of 6deg head-down tilt BR over a broad range of BP perturbations. METHODS: Nineteen normal volunteers (12M, 7F) were tested one day before BR, and then near BR days 30, 60 and 90. BP was pharmacologically altered by continuous infusions of phenylephrine (PE) and sodium nitroprusside (SNP). Electrocardiogram and continuous BP were collected during 10 min of normal saline (NS), followed by increasing concentrations of PE (10 min each of 0.4, 0.8 and 1.6 micro-g/kg/min). After a 20 min break, NS was infused again for 10 min, followed by increasing concentrations of SNP (10 min each of 0.4, 0.8, 1.2 micro-g/kg/min). Baroreceptor sensitivity was measured as the slope of a sequence of 3 or more beats in which the systolic BP and following R-R interval (RR) both increased or decreased. Spectral heart rate variability (HRV) and mean RR were analyzed using data from only the NS infusions. Two-way repeated-measures analysis of variance was performed to examine the effects of BR and gender. RESULTS: RR decreased (p<0.001) from pre- BR across BR days. High frequency in normalized units, a measure of parasympathetic activity, decreased with BR (p=0.027) and was lower (p=0.046) in men (0.39+/-0.02, mean+/-SEM) than women (0.48+/-0.02). The spontaneous baroreflex slope, our measure of BRS, increased with PE and decreased with SNP across BR (p<0.001). The percentage decrease in BRS from pre- to post-BR appeared to be larger in women (43.6+/-7.0%) than in men (31.3+/-3.9%, p=0.06). CONCLUSION: Parasympathetic activity and baroreflex sensitivity decrease during 90 days of BR, and BRS tends to diminish more in women than in men.

Impairments in prehension produced by early postnatal sensory motor cortex activity blockade.

PubMed

Martin, J H; Donarummo, L; Hacking, A

2000-02-01

This study examined the effects of blocking neural activity in sensory motor cortex during early postnatal development on prehension. We infused muscimol, either unilaterally or bilaterally, into the sensory motor cortex of cats to block activity continuously between postnatal weeks 3-7. After stopping infusion, we trained animals to reach and grasp a cube of meat and tested behavior thereafter. Animals that had not received muscimol infusion (unilateral saline infusion; age-matched) reached for the meat accurately with small end-point errors. They grasped the meat using coordinated digit flexion followed by forearm supination on 82.7% of trials. Performance using either limb did not differ significantly. In animals receiving unilateral muscimol infusion, reaching and grasping using the limb ipsilateral to the infusion were similar to controls. The limb contralateral to infusion showed significant increases in systematic and variable reaching end-point errors, often requiring subsequent corrective movements to contact the meat. Grasping occurred on only 14.8% of trials, replaced on most trials by raking without distal movements. Compensatory adjustments in reach length and angle, to maintain end-point accuracy as movements were started from a more lateral position, were less effective using the contralateral limb than ipsilateral limb. With bilateral inactivations, the form of reaching and grasping impairments was identical to that produced by unilateral inactivation, but the magnitude of the reaching impairments was less. We discuss these results in terms of the differential effects of unilateral and bilateral inactivation on corticospinal tract development. We also investigated the degree to which these prehension impairments after unilateral blockade reflect control by each hemisphere. In animals that had received unilateral blockade between postnatal weeks (PWs) 3 and 7, we silenced on-going activity (after PW 11) during task performance using continuous muscimol infusion. We inactivated the right (previously active) and then the left (previously silenced) sensory motor cortex. Inactivation of the ipsilateral (right) sensory motor cortex produced a further increase in systematic error and less frequent normal grasping. Reinactivation of the contralateral (left) cortex produced larger increases in reaching and grasping impairments than those produced by ipsilateral inactivation. This suggests that the impaired limb receives bilateral sensory motor cortex control but that control by the contralateral (initially silenced) cortex predominates. Our data are consistent with the hypothesis that the normal development of skilled motor behavior requires activity in sensory motor cortex during early postnatal life.

APA national audit of pediatric opioid infusions.

PubMed

Morton, Neil S; Errera, Agata

2010-02-01

A prospective audit of neonates, infants, and children receiving opioid infusion techniques managed by pediatric acute pain teams from across the United Kingdom and Eire was undertaken over a period of 17 months. The aim was to determine the incidence, nature, and severity of serious clinical incidents (SCIs) associated with the techniques of continuous opioid infusion, patient-controlled analgesia, and nurse-controlled analgesia in patients aged 0-18. The audit was funded by the Association of Paediatric Anaesthetists (APA) and performed by the acute pain services of 18 centers throughout the United Kingdom. Data were submitted weekly via a web-based return form designed by the Document Capture Company that documented data on all patients receiving opioid infusions and any SCIs. Eight categories of SCI were identified in advance, and the reported SCIs were graded in terms of severity (Grade 1 (death/permanent harm); Grade 2 (harm but full recovery and resulting in termination of the technique or needing significant intervention); Grade 3 (potential but no actual harm). Data were collected over a period of 17 months (25/06/07-25/11/08) and stored on a secure server for analysis. Forty-six SCIs were reported in 10 726 opioid infusion techniques. One Grade 1 incident (1 : 10,726) of cardiac arrest occurred and was associated with aspiration pneumonitis and the underlying neurological condition, neurocutaneous melanosis. Twenty-eight Grade 2 incidents (1 : 383) were reported of which half were respiratory depression. The seventeen Grade 3 incidents (1 : 631) were all drug errors because of programming or prescribing errors and were all reported by one center. The overall incidence of 1 : 10,000 of serious harm with opioid infusion techniques in children is comparable to the risks with pediatric epidural infusions and central blocks identified by two recent UK national audits (1,2). Avoidable factors were identified including prescription and pump programming errors, use of concurrent sedatives or opioids by different routes and overgenerous dosing in infants. Early respiratory depression in patients with specific risk factors, such as young age, neurodevelopmental, respiratory, or cardiac comorbidities, who are receiving nurse-controlled analgesia or continuous opioid infusion suggests that closer monitoring for at least 2 h is needed for these cases. As a result of this audit, we can provide parents with better information on relative risks to help the process of informed consent.

Effect of Admission Oral Diuretic Dose on Response to Continuous versus Bolus Intravenous Diuretics in Acute Heart Failure: An Analysis from DOSE-AHF

PubMed Central

Shah, Ravi V.; McNulty, Steven; O'Connor, Christopher M.; Felker, G. Michael; Braunwald, Eugene; Givertz, Michael M.

2014-01-01

Background Results from the Diuretic Optimization Strategies in Acute Heart Failure (DOSE-AHF) study suggest that an initial continuous infusion of loop diuretics is not superior to bolus dosing with regard to clinical endpoints in AHF. We hypothesized that outpatient furosemide dose was associated with congestion and poorer renal function, and explored the hypothesis that a continuous infusion may be more effective in patients on higher outpatient diuretic doses. Methods DOSE-AHF randomized 308 patients within 24 hours of admission to high vs. low initial intravenous diuretic dose given as either a continuous infusion or bolus. We compared baseline characteristics and assessed associations between mode of administration (bolus vs. continuous) and outcomes in patients receiving high-dose (≥120 mg furosemide equivalent, n=177) versus low-dose (<120 mg furosemide equivalent, n=131) outpatient diuretics. Results Patients on higher doses of furosemide were less frequently on renin-angiotensin system inhibitors (P=.01), and had worse renal function and more advanced symptoms. There was a significant interaction between outpatient dose and mode of therapy (P=0.01) with respect to net fluid loss at 72 hours after adjusting for creatinine and intensification strategy. Admission diuretic dose was associated with an increased risk of death or rehospitalization at 60 days (adjusted HR=1.08 per 20-mg increment in dose, 95% CI 1.01–1.16, P=.03). Conclusions In acute HF, patients on higher diuretic doses have greater disease severity, and may benefit from an initial bolus strategy. PMID:23194486

The effect of dexmedetomidine continuous infusion as an adjuvant to general anesthesia on sevoflurane requirements: A study based on entropy analysis.

PubMed

Patel, Chirag Ramanlal; Engineer, Smita R; Shah, Bharat J; Madhu, S

2013-07-01

Dexmedetomidine, a α2 agonist as an adjuvant in general anesthesia, has anesthetic and analgesic-sparing property. To evaluate the effect of continuous infusion of dexmedetomidine alone, without use of opioids, on requirement of sevoflurane during general anesthesia with continuous monitoring of depth of anesthesia by entropy analysis. Sixty patients were randomly divided into 2 groups of 30 each. In group A, fentanyl 2 mcg/kg was given while in group B, dexmedetomidine was given intravenously as loading dose of 1 mcg/kg over 10 min prior to induction. After induction with thiopentone in group B, dexmedetomidine was given as infusion at a dose of 0.2-0.8 mcg/kg. Sevoflurane was used as inhalation agent in both groups. Hemodynamic variables, sevoflurane inspired fraction (FIsevo), sevoflurane expired fraction (ETsevo), and entropy (Response entropy and state entropy) were continuously recorded. Statistical analysis was done by unpaired student's t-test and Chi-square test for continuous and categorical variables, respectively. A P-value < 0.05 was considered significant. The use of dexmedetomidine with sevoflurane was associated with a statistical significant decrease in ETsevo at 5 minutes post-intubation (1.49 ± 0.11) and 60 minutes post-intubation (1.11 ±0.28) as compared to the group A [1.73 ±0.30 (5 minutes); 1.68 ±0.50 (60 minutes)]. There was an average 21.5% decrease in ETsevo in group B as compared to group A. Dexmedetomidine, as an adjuvant in general anesthesia, decreases requirement of sevoflurane for maintaining adequate depth of anesthesia.

Ethical Tensions in the Pain Management of an End-Stage Cancer Patient with Evidence of Opioid Medication Diversion.

PubMed

Venkat, Arvind; Kim, David

2016-06-01

At the end of life, pain management is commonly a fundamental part of the treatment plan for patients where curative measures are no longer possible. However, the increased recognition of opioid diversion for secondary gain coupled with efforts to treat patients in the home environment towards the end of life creates the potential for ethical dilemmas in the palliative care management of terminal patients in need of continuous pain management. We present the case of an end-stage patient with rectal cancer who required a continuous residential narcotic infusion of fentanyl for pain control due to metastatic disease. His functional status was such that he had poor oral intake and ability to perform other activities of daily living, but was able to live at home with health agency nursing care. The patient presented to this institution with a highly suspect history of having lost his fentanyl infusion in a residential accident and asking for a refill to continue home therapy. The treating physicians had concerns of diversion of the infusion medication by caregivers and were reluctant to continue the therapeutic relationship with the patient. This case exemplifies the tension that can exist between wanting to continue with palliative care management of an end-stage patient and the fear of providers when confronted by evidence of potential diversion of opioid analgesic medications. We elucidate how an ethical framework based on a combination of virtue and narrative/relationship theories with reference to proportionality can guide physicians to a pragmatic resolution of these difficult situations.

Refractory Status Epilepticus in Children: intention-to-treat with continuous infusions of midazolam and pentobarbital

PubMed Central

Tasker, Robert C; Goodkin, Howard P; Fernández, Iván Sánchez; Chapman, Kevin E; Abend, Nicholas S; Arya, Ravindra; Brenton, James N; Carpenter, Jessica L; Gaillard, William D; Glauser, Tracy A; Goldstein, Joshua; Helseth, Ashley R; Jackson, Michele C; Kapur, Kush; Mikati, Mohamad A; Peariso, Katrina; Wainwright, Mark S; Wilfong, Angus A; Williams, Korwyn; Loddenkemper, Tobias

2016-01-01

Objective To describe pediatric patients with convulsive refractory status epilepticus (RSE) in whom there is intention-to-use an intravenous anesthetic for seizure control. Design Two-year prospective observational study evaluating patients (age range one month to 21 years) with RSE not responding to two antiepileptic drug classes and treated with continuous infusion of anesthetic agent. Setting Nine pediatric hospitals in the United States. Patients In a cohort of 111 patients with RSE (median age 3.7 years, 50% male), 54 (49%) underwent continuous infusion of anesthetic treatment. Main Results The median (interquartile range, IQR) intensive care unit length-of-stay was 10 (3–20) days. Up to four ‘cycles’ of serial anesthetic therapy were used and seizure termination was achieved in 94% by the second cycle. Seizure duration in controlled patients was 5.9 (1.9–34) hours for the first cycle, and longer when a second cycle was required (30 [4,−120] hours, p=0.048). Midazolam was the most frequent first-line anesthetic agent (78%); pentobarbital was the most frequently used second-line agent after midazolam failure (82%). An electroencephalographic endpoint was used in over half of the patients; higher midazolam dosing was used with a burst suppression endpoint. In midazolam non-responders, transition to a second agent occurred after a median of one day. Most patients (94%) experienced seizure termination with these two therapies. Conclusions Midazolam and pentobarbital remains the mainstay of continuous infusion therapy for RSE in the pediatric patient. The majority of patients experience seizure termination within a median of 30 hours. These data have implications for the design and feasibility of future intervention trials. That is, testing a new anesthetic anticonvulsant after failure of both midazolam and pentobarbital is unlikely to be feasible in a pediatric study, whereas a decision to test an alternative to pentobarbital, after midazolam failure, may be possible in a multicenter multinational study. PMID:27500721

Refractory Status Epilepticus in Children: Intention to Treat With Continuous Infusions of Midazolam and Pentobarbital.

PubMed

Tasker, Robert C; Goodkin, Howard P; Sánchez Fernández, Iván; Chapman, Kevin E; Abend, Nicholas S; Arya, Ravindra; Brenton, James N; Carpenter, Jessica L; Gaillard, William D; Glauser, Tracy A; Goldstein, Joshua; Helseth, Ashley R; Jackson, Michele C; Kapur, Kush; Mikati, Mohamad A; Peariso, Katrina; Wainwright, Mark S; Wilfong, Angus A; Williams, Korwyn; Loddenkemper, Tobias

2016-10-01

To describe pediatric patients with convulsive refractory status epilepticus in whom there is intention to use an IV anesthetic for seizure control. Two-year prospective observational study evaluating patients (age range, 1 mo to 21 yr) with refractory status epilepticus not responding to two antiepileptic drug classes and treated with continuous infusion of anesthetic agent. Nine pediatric hospitals in the United States. In a cohort of 111 patients with refractory status epilepticus (median age, 3.7 yr; 50% male), 54 (49%) underwent continuous infusion of anesthetic treatment. The median (interquartile range) ICU length of stay was 10 (3-20) days. Up to four "cycles" of serial anesthetic therapy were used, and seizure termination was achieved in 94% by the second cycle. Seizure duration in controlled patients was 5.9 (1.9-34) hours for the first cycle and longer when a second cycle was required (30 [4-120] hr; p = 0.048). Midazolam was the most frequent first-line anesthetic agent (78%); pentobarbital was the most frequently used second-line agent after midazolam failure (82%). An electroencephalographic endpoint was used in over half of the patients; higher midazolam dosing was used with a burst suppression endpoint. In midazolam nonresponders, transition to a second agent occurred after a median of 1 day. Most patients (94%) experienced seizure termination with these two therapies. Midazolam and pentobarbital remain the mainstay of continuous infusion therapy for refractory status epilepticus in the pediatric patient. The majority of patients experience seizure termination within a median of 30 hours. These data have implications for the design and feasibility of future intervention trials. That is, testing a new anesthetic anticonvulsant after failure of both midazolam and pentobarbital is unlikely to be feasible in a pediatric study, whereas a decision to test an alternative to pentobarbital, after midazolam failure, may be possible in a multicenter multinational study.

A Multicenter, Randomized, Triple-Masked, Placebo-Controlled Trial of The Effect of Ambulatory Continuous Femoral Nerve Blocks on Discharge-Readiness Following Total Knee Arthroplasty In Patients on General Orthopaedic Wards

PubMed Central

Ilfeld, Brian M.; Mariano, Edward R.; Girard, Paul J.; Loland, Vanessa J.; Meyer, R. Scott; Donovan, John F.; Pugh, George A.; Le, Linda T.; Sessler, Daniel I.; Shuster, Jonathan J.; Theriaque, Douglas W.; Ball, Scott T.

2010-01-01

A continuous femoral nerve block (cFNB) involves the percutaneous insertion of a catheter adjacent to the femoral nerve, followed by a local anesthetic infusion, improving analgesia following total knee arthroplasty (TKA). Portable infusion pumps allow infusion continuation following hospital discharge, raising the possibility of decreasing hospitalization duration. We therefore used a multicenter, randomized, triple-masked, placebo-controlled study design to test the primary hypothesis that a four-day ambulatory cFNB decreases the time until each of three predefined readiness-for-discharge criteria (adequate analgesia, independence from intravenous opioids, and ambulation ≥ 30 meters) are met following TKA compared with an overnight inpatient-only cFNB. Preoperatively, all patients received a cFNB with perineural ropivacaine 0.2% from surgery until the following morning, at which time they were randomized to either continue perineural ropivacaine (n=39) or switch to normal saline (n=38). Patients were discharged with their cFNB and portable infusion pump as early as postoperative day three. Patients given four days of perineural ropivacaine attained all three criteria in a median (25th–75th percentiles) of 47 (29–69) hours, compared with 62 (45–79) hours for those of the control group (Estimated ratio=0.80, 95% confidence interval: 0.66–1.00; p=0.028). Compared with controls, patients randomized to ropivacaine met the discharge criterion for analgesia in 20 (0–38) vs. 38 (15–64) hours (p=0.009), and intravenous opioid independence in 21 (0–37) vs. 33 (11–50) hours (p=0.061). We conclude that a four-day ambulatory cFNB decreases the time to reach three important discharge criteria by an estimated 20% following TKA compared with an overnight cFNB, primarily by improving analgesia. PMID:20573448

Winged Metal Needles versus Plastic Winged and Nonwinged Cannulae for Subcutaneous Infusions in Palliative Care: A Quality Improvement Project To Enhance Patient Care and Medical Staff Safety in a Singaporean Hospital.

PubMed

Neo, Shirlyn Hui-Shan; Khemlani, Mansha Hari; Sim, Lai Kiow; Seah, Angeline Soek Tian

2016-03-01

A comparison of metal needles and plastic cannulae (winged and nonwinged) for continuous subcutaneous infusion was done during a quality improvement project to reduce device-induced complications at our hospital. Design, Setting, and Measurements: Data were collected on incidence of site reactions (bruising, swelling, erythema, and blisters); mechanical complications (kinking and dislodgement); device durability; type, and volume of medications; and incidence of needle-stick injuries. All infusion devices used for patients in the Palliative Care Service from February 3 to March 26, 2014 were studied. Devices examined were: winged metal needle (Venofix(®), 23G, B. Braun Melsungen AG, Melsungen, Germany), winged vialon cannula (BD Nexiva™, 24G, Becton Dickinson Infusion Therapy Systems Inc., Sandy, UT), and nonwinged polyurethane cannula (Introcan Safety(®), 24G, B. Braun Medical, Mundelein, IL). Thirty devices (10 per type) were used. Incidence of site reactions was 50.0%, 10.0%, and 0.0% for the metal needles, polyurethane cannulae, and vialon cannulae, respectively. Incidence of mechanical complications was 20.0% for the polyurethane cannulae and 0.0% for the metal needles and vialon cannulae. Duration of use was up to 60 hours, 83 hours, and 113 hours for the metal needles, polyurethane cannulae, and vialon cannulae, respectively. Daily volumes infused were up to 28.9 mL, 60.0 mL, and 29.4 mL for the metal needles, polyurethane cannulae, and vialon cannulae, respectively. No needle-stick injuries occurred. The winged vialon cannula was the most durable, with no site reactions or mechanical complications, tolerating a volume comparable to that of the metal needle. We suggest its utilization for continuous subcutaneous infusions and consideration of future randomized controlled trials with an integrated economic evaluation for further in-depth comparisons of subcutaneous indwelling devices.

Effects of l-arginine pretreatment on nitric oxide metabolism and hepatosplanchnic perfusion during porcine endotoxemia1234

PubMed Central

Bruins, Maaike J; Kessels, Fons; Luiking, Yvette C; Lamers, Wouter H; Deutz, Nicolaas EP

2011-01-01

Background: Sepsis is accompanied by an increased need for and a decreased supply of arginine, reflecting a condition of arginine deficiency. Objective: The objective was to evaluate the effects of l-arginine pretreatment on arginine–nitric oxide (NO) production and hepatosplanchnic perfusion during subsequent endotoxemia. Design: In a randomized controlled trial, pigs (20–25 kg) received 3 μg ⋅ kg−1 ⋅ min−1 lipopolysaccharide (LPS; 5 endotoxin units/ng) intravenously and saline resuscitation. l-Arginine (n = 8; 5.3 μmol ⋅ kg−1 ⋅ min−1) or saline (n = 8) was infused starting 12 h before LPS infusion and continued for 24 h after the endotoxin infusion ended. Whole-body appearance rates, portal-drained viscera (PDV), and liver fluxes of arginine, citrulline, NO, and arginine de novo synthesis were measured by using stable-isotope infusion of [15N2]arginine and [13C-2H2]citrulline. Hepatosplanchnic perfusion was assessed by using a primed continuous infusion of para-aminohippuric acid and jejunal intramucosal partial pressure of carbon dioxide and was related to systemic hemodynamics. Results: Arginine supplementation before LPS increased whole-body NO production in the PDV but not in the liver. Furthermore, it increased blood flow in the portal vein but not in the aorta and hepatic artery. During endotoxin infusion, arginine pretreatment was associated with an increased whole-body arginine appearance and NO production in the gut. Additional effects included a preserved mean arterial pressure, the prevention of an increase in pulmonary arterial pressure, an attenuated metabolic acidosis, and an attenuated increase in the intramucosal partial pressure of carbon dioxide. Conclusion: Arginine treatment starting before endotoxemia appears to be beneficial because it improves hepatosplanchnic perfusion and oxygenation during prolonged endotoxemia, probably through an enhancement in NO synthesis, without causing deleterious systemic side effects. PMID:21508091

Cost-effectiveness analysis of levobupivacaine 0.5 %, a local anesthetic, infusion in the surgical wound after modified radical mastectomy.

PubMed

Ferreira Laso, Lourdes; López Picado, Amanda; Antoñanzas Villar, Fernando; Lamata de la Orden, Laura; Ceballos Garcia, Mar; Ibañez López, Carolina; Pipaon Ruilope, Lorena; Lamata Hernandez, Felix; Valero Martinez, Cesar; Aizpuru, Felipe; Hernandez Chaves, Roberto

2015-09-01

Effective treatment of postoperative pain contributes to decreasing the rate of complications as well as the total cost of the operated patients. The aim of this study was to analyze the costs and the efficiency of use of continuous infusion of levobupivacaine 0.5 % with the help of an infusion pump in modified radical mastectomy. A cost calculation of the analgesic procedures (continuous infusion of levobupivacaine 0.5 % [levobupivacaine group (LG)] or saline [saline group (SG)] (2 ml/h 48 h) has been carried out based on the data of a previous clinical trial (double-blind randomized study) of patients who underwent modified radical mastectomy surgery. The measure of the effectiveness was the point reduction of pain derived from the verbal numeric rating scale (VNRS). The usual incremental cost-effectiveness ratio (ICER) was performed. Considering only the intravenous analgesia, overall costs were lower in LG, as less analgesia was used (EUR14.06 ± 7.89 vs. 27.47 ± 14.79; p < 0.001). In this study the costs of the infusion pump were not calculated as it was used by both groups and they offset each other. However, if the infusion pump costs were included, costs would be higher in the LG, (EUR91.89 ± 7.89 vs. 27.47 ± 14.79; p < 0.001) and then the ICER was -8.51, meaning that for every extra point of decrease in the pain verbal numerical rating score over the 2-day period, the cost increased by EUR8.51. Infiltration of local anesthetics is an effective technique for controlling postoperative pain and the associated added costs are relatively low in relation to the total cost of mastectomy, therefore providing patients with a higher quality of care in the prevention of pain. clinicaltrials.gov: reference number NCT01389934. http://clinicaltrials.gov/show/NCT01389934

Prolonged adenosine triphosphate infusion and exercise hyperemia in humans.

PubMed

Shepherd, John R A; Joyner, Michael J; Dinenno, Frank A; Curry, Timothy B; Ranadive, Sushant M

2016-09-01

In humans, intra-arterial ATP infusion in limbs mimics many features of exercise hyperemia. However, it remains unknown whether ATP can evoke the prolonged vasodilation seen during exercise. Therefore, we addressed two questions during a continuous 3-h brachial artery infusion of ATP [20 μg·100 ml forearm volume (FAV)(-1)·min(-1)]: 1) would skeletal muscle blood flow remain robust or wane over time (tachyphylaxis); and 2) would the hyperemic response to moderate-intensity exercise performed during the ATP administration be blunted compared with that during control (saline) infusion. Nine participants (25 ± 1 yr) performed one trial consisting of seven bouts of rhythmic handgrip exercise (20 contractions/min at 20% of maximum), two bouts during saline (control), and five bouts during 180 min of continuous ATP infusion. Five minutes of ATP infusion resulted in a 710% increase in forearm vascular conductance (FVC) from control (4.8 ± 0.77 vs. 35.0 ± 5.7 ml·min(-1)·100 mmHg(-1)·dl FAV(-1), P < 0.05). Contrary to our expectations, FVC did not wane over time with values of 35.0 ± 5.7 and 36.0 ± 7.7 ml·min(-1)·100 mmHg(-1)·dl FAV(-1) (P > 0.05), seen prior to the exercise bouts at 5 vs. 150 min, respectively. During superimposed exercise, FVC increased from 35.0 ± 5.7 to 49.6 ± 5.4 ml·min(-1)·100 mmHg(-1)·dl FAV(-1) at 5 min and 36.0 ± 7.7 to 54.5 ± 5.0 at 150 min (P < 0.05). Our findings demonstrate ATP vasodilation is prolonged over time without tachyphylaxis; however, exercise hyperemia responses remain intact. Our results challenge the metabolic theory of exercise hyperemia, suggesting a disconnect between matching of blood flow and metabolic demand. Copyright © 2016 the American Physiological Society.

Continuing Education in the Humanities for Practicing Health Care Professionals: A Case Study.

ERIC Educational Resources Information Center

Burns, Chester R.

1982-01-01

This report of a four-week continuing education seminar in the history of medical ethics for health care practitioners describes the participants, the process, the evaluation, and the outcomes of this infusion of the humanities into the health sciences. (SK)

Drag penalty due to the asperities in the substrate of super-hydrophobic and liquid infused surfaces

NASA Astrophysics Data System (ADS)

Garcia Cartagena, Edgardo J.; Arenas, Isnardo; Leonardi, Stefano

2017-11-01

Direct numerical simulations of two superposed fluids in a turbulent channel with a textured surface made of pinnacles of random height have been performed. The viscosity ratio between the two fluids are N =μo /μi = 50 (μo and μi are the viscosities of outer and inner fluid respectively) mimicking a super-hydrophobic surface (water over air) and N=2.5 (water over heptane) resembling a liquid infused surface. Two set of simulations have been performed varying the Reynolds number, Reτ = 180 and Reτ = 390 . The interface between the two fluids is flat simulating infinite surface tension. The position of the interface between the two fluids has been varied in the vertical direction from the base of the substrate (what would be a rough wall) to the highest point of the roughness. Drag reduction is very sensitive to the position of the interface between the two fluids. Asperities above the interface induce a large form drag and diminish considerably the drag reduction. When the mean height of the surface measured from the interface in the outer fluid is greater than one wall unit, k+ > 1 , the drag increases with respect to a smooth wall. Present results provide a guideline to the accuracy required in manufacturing super-hydrophobic and liquid infused surfaces. This work was supported under ONR MURI Grants N00014-12-0875 and N00014-12- 1-0962, Program Manager Dr. Ki-Han Kim. Numerical simulations were performed on the Texas Advanced Computer Center.

Pharmacokinetics and pharmacodynamics of epsilon-aminocaproic acid in horses.

PubMed

Ross, Julie; Dallap, Barbara L; Dolente, Brett A; Sweeney, Raymond W

2007-09-01

To determine the pharmacokinetics and pharmacodynamics of epsilon-aminocaproic acid (EACA), including the effects of EACA on coagulation and fibrinolysis in healthy horses. 6 adult horses. Each horse received 3.5 mg of EACA/kg/min for 20 minutes, i.v. Plasma EACA concentration was measured before (time 0), during, and after infusion. Coagulation variables and plasma alpha(2)-antiplasmin activity were evaluated at time 0 and 4 hours after infusion; viscoelastic properties of clot formation were assessed at time 0 and 0.5, 1, and 4 hours after infusion. Plasma concentration versus time data were evaluated by use of a pharmacokinetic analysis computer program. Drug disposition was best described by a 2-compartment model with a rapid distribution phase, an elimination half-life of 2.3 hours, and mean residence time of 2.5 +/- 0.5 hours. Peak plasma EACA concentration was 462.9 +/- 70.1 microg/mL; after the end of the infusion, EACA concentration remained greater than the proposed therapeutic concentration (130 microg/mL) for 1 hour. Compared with findings at 0 minutes, EACA administration resulted in no significant change in plasma alpha(2)-antiplasmin activity at 1 or 4 hours after infusion. Thirty minutes after infusion, platelet function was significantly different from that at time 0 and 1 and 4 hours after infusion. The continuous rate infusion that would maintain proposed therapeutic plasma concentrations of EACA was predicted (ie, 3.5 mg/kg/min for 15 minutes, then 0.25 mg/kg/min). Results suggest that EACA has potential clinical use in horses for which improved clot maintenance is desired.

Incontinence Morbidity Following Radical Prostatectomy: Psychosocial Impact on African American and White Men

DTIC Science & Technology

2005-07-01

continuous subcutaneous infusion and basal rate subcutaneous infusion plus PCA in cancer pain: a pilot study. (Review) ONS Nursing Scan in Oncology, 2 (6...teaching, medical, nursing , psychosocial, and follow-up care . Thus, in contrast to many of the men in the larger cohort, they believed they were...informed about their treatment decision and spoke very highly of the caring , professional, medical and nursing care they received. Two men who underwent the

High Dose Proton Pump Inhibitor Infusion Versus Bolus Injection for the Prevention of Bleeding After Endoscopic Submucosal Dissection: Prospective Randomized Controlled Study.

PubMed

Choi, Cheol Woong; Kang, Dae Hwan; Kim, Hyung Wook; Hong, Joung Boom; Park, Su Bum; Kim, Su Jin; Cho, Mong

2015-07-01

A high dose of continuous intravenous infusion of proton pump inhibitor (PPI) is the standard treatment for peptic ulcer bleeding. The optimal dose for the prevention of bleeding after endoscopic submucosal dissection (ESD) is unclear. The purpose of this study was to determine whether stronger acid suppression more effectively prevents bleeding and high risk ulcer stigma (HRS) after gastric ESD. A total of 273 patients who underwent ESD were randomly assigned to one of two treatment groups: the continuous infusion group and the bolus injection group. Second-look endoscopy was performed on the following day after ESD. The incidences and risk factors of HRS identified by second-look endoscopy and delayed bleeding were analyzed. There were no differences in the incidences of HRS and delayed bleeding between two treatment groups. The incidence of HRS was 15.8 % (43/273) and the gross morphology (flat or depressed) was identified as a significant factor associated with HRS. The incidence of delayed bleeding was 8.4 % (23/273) and the gross morphology (flat) and the presence of submucosal invasive cancer were identified as the associated risk factors for delayed bleeding. The incidences of delayed bleeding and HRS identified by second-look endoscopy were not affected by PPI infusion methods. Flat or depressed morphologic lesions and submucosal invasive cancer should be closely monitored.

Longitudinal infusion of a complex of insulin-like growth factor-I and IGF-binding protein-3 in five preterm infants: pharmacokinetics and short-term safety.

PubMed

Ley, David; Hansen-Pupp, Ingrid; Niklasson, Aimon; Domellöf, Magnus; Friberg, Lena E; Borg, Jan; Löfqvist, Chatarina; Hellgren, Gunnel; Smith, Lois E H; Hård, Anna-Lena; Hellström, Ann

2013-01-01

In preterm infants, low levels of insulin-like growth factor-I (IGF-I) and IGF binding protein 3 (IGFBP-3) are associated with impaired brain growth and retinopathy of prematurity (ROP). Treatment with IGF-I/IGFBP-3 may be beneficial for brain development and may decrease the prevalence of ROP. In a phase II pharmacokinetics and safety study, five infants (three girls) with a median (range) gestational age (GA) of 26 wk + 6 d (26 wk + 0 d to 27 wk + 2 d) and birth weight of 990 (900-1,212) g received continuous intravenous infusion of recombinant human (rh)IGF-I/rhIGFBP-3. Treatment was initiated during the first postnatal day and continued for a median (range) duration of 168 (47-168) h in dosages between 21 and 111 µg/kg/24 h. Treatment with rhIGF-I/rhIGFBP-3 was associated with higher serum IGF-I and IGFBP-3 concentrations (P < 0.001) than model-predicted endogenous levels. Of 74 IGF-I samples measured during study drug infusion, 37 (50%) were within the target range, 4 (5%) were above, and 33 (45%) were below. The predicted dose of rhIGF-I/rhIGFBP-3 required to establish circulating levels of IGF-I within the intrauterine range in a 1,000 g infant was 75-100 µg/kg/24 h. No hypoglycemia or other adverse effects were recorded. In this study, continuous intravenous infusion of rhIGF-I/rhIGFBP-3 was effective in increasing serum concentrations of IGF-I and IGFBP-3, and was found to be safe.

Comparison of Propofol-Remifentanil Versus Propofol-Ketamine Deep Sedation for Third Molar Surgery

PubMed Central

Kramer, Kyle J.; Ganzberg, Steven; Prior, Simon; Rashid, Robert G.

2012-01-01

This study aimed to compare continuous intravenous infusion combinations of propofol-remifentanil and propofol-ketamine for deep sedation for surgical extraction of all 4 third molars. In a prospective, randomized, double-blinded controlled study, participants received 1 of 2 sedative combinations for deep sedation for the surgery. Both groups initially received midazolam 0.03 mg/kg for baseline sedation. The control group then received a combination of propofol-remifentanil in a ratio of 10 mg propofol to 5 μg of remifentanil per milliliter, and the experimental group received a combination of propofol-ketamine in a ratio of 10 mg of propofol to 2.5 mg of ketamine per milliliter; both were given at an initial propofol infusion rate of 100 μg/kg/min. Each group received an induction loading bolus of 500 μg/kg of the assigned propofol combination along with the appropriate continuous infusion combination . Measured outcomes included emergence and recovery times, various sedation parameters, hemodynamic and respiratory stability, patient and surgeon satisfaction, postoperative course, and associated drug costs. Thirty-seven participants were enrolled in the study. Both groups demonstrated similar sedation parameters and hemodynamic and respiratory stability; however, the ketamine group had prolonged emergence (13.6 ± 6.6 versus 7.1 ± 3.7 minutes, P = .0009) and recovery (42.9 ± 18.7 versus 24.7 ± 7.6 minutes, P = .0004) times. The prolonged recovery profile of continuously infused propofol-ketamine may limit its effectiveness as an alternative to propofol-remifentanil for deep sedation for third molar extraction and perhaps other short oral surgical procedures, especially in the ambulatory dental setting. PMID:23050750

First application of a transcutaneous optical single-port glucose monitoring device in patients with type 1 diabetes mellitus.

PubMed

Rumpler, M; Mader, J K; Fischer, J P; Thar, R; Granger, J M; Deliane, F; Klimant, I; Aberer, F; Sinner, F; Pieber, T R; Hajnsek, M

2017-02-15

The combination of continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion can be used to improve the treatment of patients with diabetes. The aim of this study was to advance an existing preclinical single-port system for clinical application by integrating the sensors of a phosphorescence based CGM system into a standard insulin infusion set. The extracorporeal optical phase fluorimeter was miniaturised and is now comparable with commercial CGM systems regarding size, weight and wear comfort. Sensor chemistry was adapted to improve the adhesion of the sensor elements on the insulin infusion set. In-vitro tests showed a linear correlation of R 2 =0.998 between sensor values and reference glucose values in the range of 0-300mg/dl. Electrical and cytotoxicity tests showed no negative impact on human health. Two single-port devices were tested in each of 12 patients with type 1 diabetes mellitus in a clinical set-up for 12h. Without additional data processing, the overall median absolute relative difference (median ARD) was 22.5%. For some of the used devices the median ARD was even well below 10%. The present results show that individual glucose sensors performance of the single-port system is comparable with commercial CGM systems but further improvements are needed. The new system offers a high extent of safety and usability by combining insulin infusion and continuous glucose measurement in a single-port system which could become a central element in an artificial pancreas for an improved treatment of patients with type 1 diabetes mellitus. Copyright © 2016 Elsevier B.V. All rights reserved.

Continuous delivery of naltrexone and nalmefene leads to tolerance in reducing alcohol drinking and to supersensitivity of brain opioid receptors.

PubMed

Korpi, Esa R; Linden, Anni-Maija; Hytönen, Heidi R; Paasikoski, Nelli; Vashchinkina, Elena; Dudek, Mateusz; Herr, Deron R; Hyytiä, Petri

2017-07-01

Opioid antagonist treatments reduce alcohol drinking in rodent models and in alcohol-dependent patients, with variable efficacy across different studies. These treatments may suffer from the development of tolerance and opioid receptor supersensitivity, as suggested by preclinical models showing activation of these processes during and after subchronic high-dose administration of the short-acting opioid antagonist naloxone. In the present study, we compared equipotent low and moderate daily doses of naltrexone and nalmefene, two opioid antagonists in the clinical practice for treatment of alcoholism. The antagonists were given here subcutaneously for 7 days either as daily injections or continuous osmotic minipump-driven infusions to alcohol-preferring AA rats having trained to drink 10% alcohol in a limited access protocol. One day after stopping the antagonist treatment, [ 35 S]GTPγS autoradiography on brain cryostat sections was carried out to examine the coupling of receptors to G protein activation. The results prove the efficacy of repeated injections over infused opioid antagonists in reducing alcohol drinking. Tolerance to the reducing effect on alcohol drinking and to the enhancement of G protein coupling to μ-opioid receptors in various brain regions were consistently detected only after infused antagonists. Supersensitivity of κ-opioid receptors was seen in the ventral and dorsal striatal regions especially by infused nalmefene. Nalmefene showed no clear agonistic activity in rat brain sections or at human recombinant κ-opioid receptors. The findings support the as-needed dosing practice, rather than the standard continual dosing, in the treatment of alcoholism with opioid receptor antagonists. © 2016 Society for the Study of Addiction.

Intra-arterial bromodeoxyuridine radiosensitization of malignant gliomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hegarty, T.J.; Thornton, A.F.; Diaz, R.F.

1990-08-01

In the 1950's it was first observed that mammalian cells exposed to the halogenated deoxyuridines were more sensitive to ultraviolet light and radiation than untreated cells. This prompted early clinical trials with bromodeoxyuridine (BUdR) which showed mixed results. More recently, several Phase I studies, while establishing the feasibility of continuous intravenous (IV) infusion of BUdR, have reported significant dose limiting skin and bone marrow toxicities and have questioned the optimal method of BUdR delivery. To exploit the high mitotic activity of malignant gliomas relative to surrounding normal brain tissue, we have developed a permanently implantable infusion pump system for safe,more » continuous intraarterial (IA) internal carotid BUdR delivery. Since July 1985, 23 patients with malignant brain tumors (18 grade 4, 5 grade 3) have been treated in a Phase I clinical trial using IA BUdR (400-600 mg/m2/day X 8 1/2 weeks) and focal external beam radiotherapy (59.4 Gy at 1.8 Gy/day in 6 1/2 weeks). Following initial biopsy/surgery the infusion pump system was implanted; BUdR infusion began 2 weeks prior to and continued throughout the 6 1/2 week course of radiotherapy. There have been no vascular complications. Side-effects in all patients have included varying degrees of anorexia, fatigue, ipsilateral forehead dermatitis, blepharitis, and conjunctivitis. Myelosuppression requiring dose reduction occurred in one patient. An overall Kaplan-Meier estimated median survival of 20 months has been achieved. As in larger controlled series, histologic grade and age are prognostically significant. We have shown in a Phase I study that IA BUdR radiosensitization is safe, tolerable, may lead to improved survival, and appears to be an efficacious primary treatment of malignant gliomas.« less

Continuous infusion of substance P into rat striatum alleviates nociceptive behavior via phosphorylation of extracellular signal-regulated kinase 1/2.

PubMed

Nakamura, Yoki; Izumi, Hiroki; Fukushige, Ryo; Shimizu, Takumi; Watanabe, Kyohei; Morioka, Norimitsu; Hama, Aldric; Takamatsu, Hiroyuki; Nakata, Yoshihiro

2014-12-01

Intraplantar injection of 0.4% formalin into the rat hind paw leads to a biphasic nociceptive response; an 'acute' phase (0-15 min) and 'tonic' phase (16-120 min), which is accompanied by significant phosphorylation of extracellular signal-regulated kinase (ERK)1/2 in the contralateral striatum at 120 min post-formalin injection. To uncover a possible relationship between the slow-onset substance P (SP) release and increased ERK1/2 phosphorylation in the striatum, continuous infusion of SP into the striatum by reverse microdialysis (0.4 μg/mL in microdialysis fiber, 1 μL/min) was performed to mimic volume neurotransmission of SP. Continuous infusion for 3 h of SP reduced the duration of 'tonic' phase nociception, and this SP effect was mediated by neurokinin 1 (NK1) receptors since pre-treatment with NK1 receptor antagonist CP96345 (10 μM) blocked the effect of SP infusion. However, formalin-induced 'tonic' phase nociception was significantly prolonged following acute injection of the MAP/ERK kinase 1/2 inhibitor PD0325901 (100 pmol) by microinjection. The coinfusion of SP and PD0325901 significantly increased the 'tonic' phase of nociception. These data demonstrate that volume transmission of striatal SP triggered by peripheral nociceptive stimulation does not lead to pain facilitation but a significant decrease of tonic nociception by the activation of the SP-NK1 receptor-ERK1/2 system. Noxious stimulation induces a slow-onset substance P (SP) release as a volume transmitter, activating extra-synaptic NK1 receptors, and evokes phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. The SP-NK1-ERK1/2 system in the striatum decreases tonic nociception. © 2014 International Society for Neurochemistry.

Longitudinal infusion of a complex of insulin-like growth factor-I and IGF-binding protein-3 in five preterm infants: pharmacokinetics and short-term safety

PubMed Central

Ley, David; Hansen-Pupp, Ingrid; Niklasson, Aimon; Domellöf, Magnus; Friberg, Lena E.; Borg, Jan; Löfqvist, Chatarina; Hellgren, Gunnel; Smith, Lois E.H.; Hård, Anna-Lena; Hellström, Ann

2014-01-01

BACKGROUND In preterm infants, low levels of insulin-like growth factor-I (IGF-I) and IGF binding protein 3 (IGFBP-3) are associated with impaired brain growth and retinopathy of prematurity (ROP). Treatment with IGF-I/IGFBP-3 may be beneficial for brain development and may decrease the prevalence of ROP. METHODS In a phase II pharmacokinetics and safety study, five infants (three girls) with a median (range) gestational age (GA) of 26 wk + 6 d (26 wk + 0 d to 27 wk + 2 d) and birth weight of 990 (900–1,212) g received continuous intravenous infusion of recombinant human (rh)IGF-I/rhIGFBP-3. Treatment was initiated during the first postnatal day and continued for a median (range) duration of 168 (47–168) h in dosages between 21 and 111 µg/kg/24 h. RESULTS Treatment with rhIGF-I/rhIGFBP-3 was associated with higher serum IGF-I and IGFBP-3 concentrations (P < 0.001) than model-predicted endogenous levels. Of 74 IGF-I samples measured during study drug infusion, 37 (50%) were within the target range, 4 (5%) were above, and 33 (45%) were below. The predicted dose of rhIGF-I/rhIGFBP-3 required to establish circulating levels of IGF-I within the intrauterine range in a 1,000 g infant was 75–100 µg/kg/24 h. No hypoglycemia or other adverse effects were recorded. CONCLUSION In this study, continuous intravenous infusion of rhIGF-I/rhIGFBP-3 was effective in increasing serum concentrations of IGF-I and IGFBP-3, and was found to be safe. PMID:23095978

Safety and clinical effect of i.v. infusion of cyclopropyl-methoxycarbonyl etomidate (ABP-700), a soft analogue of etomidate, in healthy subjects.

PubMed

Valk, B I; Absalom, A R; Meyer, P; Meier, S; den Daas, I; van Amsterdam, K; Campagna, J A; Sweeney, S P; Struys, M M R F

2018-06-01

Cyclopropyl-methoxycarbonyl metomidate, or ABP-700, is a second generation analogue of etomidate, developed to retain etomidate's beneficial haemodynamic and respiratory profile but diminishing its suppression of the adrenocortical axis. The objective of this study was to characterise the safety and efficacy of 30-min continuous infusions of ABP-700, and to assess its effect on haemodynamics and the adrenocortical response in healthy human volunteers. Five cohorts involving 40 subjects received increasing infusion doses of ABP-700, propofol 60 μg kg -1  min -1 or placebo. Safety was evaluated through adverse event (AE) monitoring, safety laboratory tests, and arterial blood gasses. Haemodynamic and respiratory stability were assessed by continuous monitoring. Adrenocortical function was analysed by adrenocorticotropic hormone (ACTH) stimulation tests. Clinical effect was measured using the modified observer's assessment of alertness/sedation (MOAA/S) and continuous bispectral index monitoring. No serious AEs were reported. Haemodynamic and respiratory effects included mild dose-dependent tachycardia, slightly elevated blood pressure, and no centrally mediated apnoea. Upon stimulation with ACTH, no adrenocortical depression was observed in any subject. Involuntary muscle movements (IMM) were reported, which were more extensive with higher dosing regimens. Higher dosages of ABP-700 were associated with deeper sedation and increased likelihood of sedation. Time to onset of clinical effect was variable throughout the cohorts and recovery was swift. Infusions of ABP-700 showed a dose-dependent hypnotic effect, and did not cause severe hypotension, severe respiratory depression, or adrenocortical suppression. The presentation and nature of IMM is a matter of concern. NTR4735. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Naloxone reversal of buprenorphine-induced respiratory depression.

PubMed

van Dorp, Eveline; Yassen, Ashraf; Sarton, Elise; Romberg, Raymonda; Olofsen, Erik; Teppema, Luc; Danhof, Meindert; Dahan, Albert

2006-07-01

The objective of this investigation was to examine the ability of the opioid antagonist naloxone to reverse respiratory depression produced by the mu-opioid analgesic, buprenorphine, in healthy volunteers. The studies were designed in light of the claims that buprenorphine is relatively resistant to the effects of naloxone. In a first attempt, the effect of an intravenous bolus dose of 0.8 mg naloxone was assessed on 0.2 mg buprenorphine-induced respiratory depression. Next, the effect of increasing naloxone doses (0.5-7 mg, given over 30 min) on 0.2 mg buprenorphine-induced respiratory depression was tested. Subsequently, continuous naloxone infusions were applied to reverse respiratory depression from 0.2 and 0.4 mg buprenorphine. All doses are per 70 kg. Respiration was measured against a background of constant increased end-tidal carbon dioxide concentration. An intravenous naloxone dose of 0.8 mg had no effect on respiratory depression from buprenorphine. Increasing doses of naloxone given over 30 min produced full reversal of buprenorphine effect in the dose range of 2-4 mg naloxone. Further increasing the naloxone dose (doses of 5 mg or greater) caused a decline in reversal activity. Naloxone bolus doses of 2-3 mg, followed by a continuous infusion of 4 mg/h, caused full reversal within 40-60 min of both 0.2 and 0.4 mg buprenorphine-induced respiratory depression. Reversal of buprenorphine effect is possible but depends on the buprenorphine dose and the correct naloxone dose window. Because respiratory depression from buprenorphine may outlast the effects of naloxone boluses or short infusions, a continuous infusion of naloxone may be required to maintain reversal of respiratory depression.

A Study of the Efficacy of Project-Based Learning Integrated with Computer-Based Simulation--STELLA

ERIC Educational Resources Information Center

Eskrootchi, Rogheyeh; Oskrochi, G. Reza

2010-01-01

Incorporating computer-simulation modelling into project-based learning may be effective but requires careful planning and implementation. Teachers, especially, need pedagogical content knowledge which refers to knowledge about how students learn from materials infused with technology. This study suggests that students learn best by actively…

Continuous infusion of antibiotics in critically ill patients.

PubMed

Smuszkiewicz, Piotr; Szałek, Edyta; Tomczak, Hanna; Grześkowiak, Edmund

2013-02-01

Antibiotics are the most commonly used drugs in intensive care unit patients and their supply should be based on pharmacokinetic/pharmacodynamic rules. The changes that occur in septic patients who are critically ill may be responsible for subtherapeutic antibiotic concentrations leading to poorer clinical outcomes. Evolving in time the disturbed pathophysiology in severe sepsis (high cardiac output, glomerular hyperfiltration) and therapeutic interventions (e.g. haemodynamically active drugs, mechanical ventilation, renal replacement therapy) alters antibiotic pharmacokinetics mainly through an increase in the volume of distribution and altered drug clearance. The lack of new and efficacious drugs and increased bacterial resistance are current problems of contemporary antibiotic therapy. Although intermittent administration is a standard clinical practice, alternative methods of antibiotic administration are sought, which may potentialise effects and reduce toxicity as well as contribute to inhibition of bacterial resistance. A wide range of studies prove that the application of continuous infusion of time-dependent antibiotics (beta-lactams, glycopeptides) is more rational than standard intermittent administration. However, there are also studies which do not confirm the advantage of one method over the other. In spite of controversy the continuous administration of this group of antibiotics is common practice, because the results of both studies point to the higher efficacy of this method in critically ill patients. Authors reviewed the literature to determine whether any clinical benefits exist for administration of time-dependent antibiotics by continuous infusion. Definite specification of the clinical advantage of administration this way over standard dosage requires a large-scale multi-centre randomised controlled trial.

Method for Continuous Monitoring of Electrospray Ion Formation

NASA Astrophysics Data System (ADS)

Metzler, Guille; Crathern, Susan; Bachmann, Lorin; Fernández-Metzler, Carmen; King, Richard

2017-10-01

A method for continuously monitoring the performance of electrospray ionization without the addition of hardware or chemistry to the system is demonstrated. In the method, which we refer to as SprayDx, cluster ions with solvent vapor natively formed by electrospray are followed throughout the collection of liquid chromatography-selected reaction monitoring data. The cluster ion extracted ion chromatograms report on the consistency of the ion formation and detection system. The data collected by the SprayDx method resemble the data collected for postcolumn infusion of analyte. The response of the cluster ions monitored reports on changes in the physical parameters of the ion source such as voltage and gas flow. SprayDx is also observed to report on ion suppression in a fashion very similar to a postcolumn infusion of analyte. We anticipate the method finding utility as a continuous readout on the performance of electrospray and other atmospheric pressure ionization processes. [Figure not available: see fulltext.

Combination of Continuous Dexmedetomidine Infusion with Titrated Ultra-Low-Dose Propofol-Fentanyl for an Awake Craniotomy

PubMed Central

Das, Samaresh; Al-Mashani, Ali; Suri, Neelam; Salhotra, Neeraj; Chatterjee, Nilay

2016-01-01

An awake craniotomy is a continuously evolving technique used for the resection of brain tumours from the eloquent cortex. We report a 29-year-old male patient who presented to the Khoula Hospital, Muscat, Oman, in 2016 with a two month history of headaches and convulsions due to a space-occupying brain lesion in close proximity with the left motor cortex. An awake craniotomy was conducted using a scalp block, continuous dexmedetomidine infusion and a titrated ultra-low-dose of propofolfentanyl. The patient remained comfortable throughout the procedure and the intraoperative neuropsychological tests, brain mapping and tumour resection were successful. This case report suggests that dexmedetomidine in combination with titrated ultra-low-dose propofolfentanyl are effective options during an awake craniotomy, ensuring optimum sedation, minimal disinhibition and a rapid recovery. To the best of the authors’ knowledge, this is the first awake craniotomy conducted successfully in Oman. PMID:27606116

Multi-Scale Impact and Compression-After-Impact Modeling of Reinforced Benzoxazine/Epoxy Composites using Micromechanics Approach

NASA Astrophysics Data System (ADS)

Montero, Marc Villa; Barjasteh, Ehsan; Baid, Harsh K.; Godines, Cody; Abdi, Frank; Nikbin, Kamran

A multi-scale micromechanics approach along with finite element (FE) model predictive tool is developed to analyze low-energy-impact damage footprint and compression-after-impact (CAI) of composite laminates which is also tested and verified with experimental data. Effective fiber and matrix properties were reverse-engineered from lamina properties using an optimization algorithm and used to assess damage at the micro-level during impact and post-impact FE simulations. Progressive failure dynamic analysis (PFDA) was performed for a two step-process simulation. Damage mechanisms at the micro-level were continuously evaluated during the analyses. Contribution of each failure mode was tracked during the simulations and damage and delamination footprint size and shape were predicted to understand when, where and why failure occurred during both impact and CAI events. The composite laminate was manufactured by the vacuum infusion of the aero-grade toughened Benzoxazine system into the fabric preform. Delamination footprint was measured using C-scan data from the impacted panels and compared with the predicated values obtained from proposed multi-scale micromechanics coupled with FE analysis. Furthermore, the residual strength was predicted from the load-displacement curve and compared with the experimental values as well.

Simulating vasogenic brain edema using chronic VEGF infusion

PubMed Central

Piazza, Martin; Munasinghe, Jeeva; Murayi, Roger; Edwards, Nancy; Montgomery, Blake; Walbridge, Stuart; Merrill, Marsha; Chittiboina, Prashant

2017-01-01

OBJECTIVE To study peritumoral brain edema (PTBE), it is necessary to create a model that accurately simulates vasogenic brain edema (VBE) without introducing a complicated tumor environment. PTBE associated with brain tumors is predominantly a result of vascular endothelial growth factor (VEGF) secreted by brain tumors, and VEGF infusion alone can lead to histological blood-brain barrier (BBB) breakdown in the absence of tumor. VBE is intimately linked to BBB breakdown. The authors sought to establish a model for VBE with chronic infusion of VEGF that can be validated by serial in-vivo MRI and histological findings. METHODS Male Fischer rats (n = 182) underwent stereotactic striatal implantation of MRI-safe brain cannulas for chronic infusion of VEGF (2–20 μg/ml). Following a preinfusion phase (4–6 days), the rats were exposed to VEGF or control rat serum albumin (1.5 μl/hr) for as long as 144 hours. Serial MRI was performed during infusion on a high-field (9.4-T) machine at 12–24, 24–36, 48–72, and 120–144 hours. Rat brains were then collected and histological analysis was performed. RESULTS Control animals and animals infused with 2 μg/ml of VEGF experienced no neurological deficits, seizure activity, or abnormal behavior. Animals treated with VEGF demonstrated a significantly larger volume (42.90 ± 3.842 mm3) of T2 hyper-attenuation at 144 hours when compared with the volume (8.585 ± 1.664 mm3) in control animals (mean difference 34.31 ± 4.187 mm3, p < 0.0001, 95% CI 25.74–42.89 mm3). Postcontrast T1 enhancement in the juxtacanalicular region indicating BBB breakdown was observed in rats undergoing infusion with VEGF. At the later time periods (120–144 hrs) the volume of T1 enhancement (34.97 ± 8.99 mm3) was significantly less compared with the region of edema (p < 0.0001). Histologically, no evidence of necrosis or inflammation was observed with VEGF or control infusion. Immunohistochemical analysis demonstrated astrocyte activation, vascular remodeling, and increased claudin-5 expression in juxtacanalicular regions. Aquaporin-4 expression was increased in both control and VEGF animals in the juxtacanalicular regions. CONCLUSIONS The results of this study show that chronic brain infusion of VEGF creates a reliable model of VBE. This model lacks necrosis and inflammation that are characteristic of previous models of VBE. The model allows for a precise investigation into the mechanism of VBE formation. The authors also anticipate that this model will allow for investigation into the mechanism of glucocorticoid action in abrogating VBE, and to test novel therapeutic strategies targeting PTBE. PMID:28059647

Inter-relationships of paclitaxel disposition, infusion duration and cremophor EL kinetics in cancer patients.

PubMed

van Zuylen, L; Gianni, L; Verweij, J; Mross, K; Brouwer, E; Loos, W J; Sparreboom, A

2000-06-01

Cremophor EL (CrEL) is a castor oil surfactant used as a vehicle for formulation of a variety of poorly water-soluble agents, including paclitaxel. Recently, we found that CrEL can influence the in vitro blood distribution of paclitaxel by reducing the free drug fraction, thereby altering drug accumulation in erythrocytes. The purpose of this study was to investigate the clinical pharmacokinetics of CrEL, and to examine inter-relationships of paclitaxel disposition, infusion duration and CrEL kinetics. The CrEL plasma clearance, studied in 17 patients for a total of 28 courses, was time dependent and increased significantly with prolongation of the infusion duration from 1 to 3 to 24 h (p<0.03). An indirect response model, applied based on use of a Hill function for CrEL concentration-dependent alteration of in vivo blood distribution of paclitaxel, was used to fit experimental data of the 3 h infusion (r2=0.733; p=0.00001). Simulations for 1 and 24 h infusions using predicted parameters and CrEL kinetic data revealed that both short and prolonged administration schedules induce a low relative net change in paclitaxel blood distribution. Our pharmacokinetic/pharmacodynamic model demonstrates that CrEL causes disproportional accumulation of paclitaxel in plasma in a 3 h schedule, but is unlikely to affect drug pharmacokinetics in this manner with alternative infusion durations.

Continuous infusion of amphotericin B deoxycholate: an innovative, low-cost strategy in antifungal treatment.

PubMed

Falci, Diego R; dos Santos, Rodrigo P; Wirth, Fernanda; Goldani, Luciano Z

2011-03-01

The combination of amphotericin B and sodium deoxycholate is the formulation most used in clinical practice. The development of new agents such as amphotericin with lipid formulations, caspofungin, voriconazole and other azolic derivatives, promoted alternatives to amphotericin B deoxycholate. However, because of the high cost of these new drugs, their use is difficult in a scenario of limited resources. A few strategies have been devised to make the use of amphotericin B deoxycholate less toxic. In this review, we seek to describe the accumulated knowledge about this molecule, with focus on its use in continuous infusion, which appears to be an alternative to reduce toxicity, while maintaining its clinical efficacy. © 2009 Blackwell Verlag GmbH.

Global Intracoronary Infusion of Allogeneic Cardiosphere-Derived Cells Improves Ventricular Function and Stimulates Endogenous Myocyte Regeneration throughout the Heart in Swine with Hibernating Myocardium

PubMed Central

Suzuki, Gen; Weil, Brian R.; Leiker, Merced M.; Ribbeck, Amanda E.; Young, Rebeccah F.; Cimato, Thomas R.; Canty, John M.

2014-01-01

Background Cardiosphere-derived cells (CDCs) improve ventricular function and reduce fibrotic volume when administered via an infarct-related artery using the “stop-flow” technique. Unfortunately, myocyte loss and dysfunction occur globally in many patients with ischemic and non-ischemic cardiomyopathy, necessitating an approach to distribute CDCs throughout the entire heart. We therefore determined whether global intracoronary infusion of CDCs under continuous flow improves contractile function and stimulates new myocyte formation. Methods and Results Swine with hibernating myocardium from a chronic LAD occlusion were studied 3-months after instrumentation (n = 25). CDCs isolated from myocardial biopsies were infused into each major coronary artery (∼33×106 icCDCs). Global icCDC infusion was safe and while ∼3% of injected CDCs were retained, they did not affect ventricular function or myocyte proliferation in normal animals. In contrast, four-weeks after icCDCs were administered to animals with hibernating myocardium, %LADWT increased from 23±6 to 51±5% (p<0.01). In diseased hearts, myocyte proliferation (phospho-histone-H3) increased in hibernating and remote regions with a concomitant increase in myocyte nuclear density. These effects were accompanied by reductions in myocyte diameter consistent with new myocyte formation. Only rare myocytes arose from sex-mismatched donor CDCs. Conclusions Global icCDC infusion under continuous flow is feasible and improves contractile function, regresses myocyte cellular hypertrophy and increases myocyte proliferation in diseased but not normal hearts. New myocytes arising via differentiation of injected cells are rare, implicating stimulation of endogenous myocyte regeneration as the primary mechanism of repair. PMID:25402428

Intrathecal Catheterization and Drug Delivery in Guinea Pigs: A Small-animal Model for Morphine-evoked Granuloma Formation.

PubMed

Eddinger, Kelly A; Rondon, Eric S; Shubayev, Veronica I; Grafe, Marjorie R; Scadeng, Miriam; Hildebrand, Keith R; Page, Linda M; Malkmus, Shelle A; Steinauer, Joanne J; Yaksh, Tony L

2016-08-01

Intrathecal infusion of opioids in dogs, sheep, and humans produces local space-occupying masses. To develop a small-animal model, the authors examined effects of intrathecal catheterization and morphine infusion in guinea pigs. Under isoflurane, polyethylene or polyurethane catheters were advanced from the cisterna magna to the lumbar enlargement. Drugs were delivered as a bolus through the externalized catheter or continuously by subcutaneous minipumps. Hind paw withdrawal to a thermal stimulus was assessed. Spinal histopathology was systematically assessed in a blinded fashion. To assist in determining catheter placement, ex vivo images were obtained using magnetic resonance imaging in several animals. Canine spinal tissue from previous intrathecal morphine studies was analyzed in parallel. (1) Polyethylene (n = 30) and polyurethane (n = 25) catheters were implanted in the lumbar intrathecal space. (2) Bolus intrathecal morphine produced a dose-dependent (20 to 40 μg/10 μl) increase in thermal escape latencies. (3) Absent infusion, a catheter-associated distortion of the spinal cord and a fibrotic investment were noted along the catheter tract (polyethylene > polyurethane). (4) Intrathecal morphine infusion (25 mg/ml/0.5 μl/h for 14 days) resulted in intrathecal masses (fibroblasts, interspersed collagen, lymphocytes, and macrophages) arising from meninges proximal to the catheter tip in both polyethylene- and polyurethane-catheterized animals. This closely resembles mass histopathology from intrathecal morphine canine studies. Continuous intrathecal infusion of morphine leads to pericatheter masses that morphologically resemble those observed in dogs and humans. This small-animal model may be useful for studying spinal drug toxicology in general and the biology of intrathecal granuloma formation in particular.

Effect of ketamine pretreatment for anaesthesia in patients undergoing percutaneous transluminal balloon angioplasty with continuous remifentanil infusion

PubMed Central

Jun, Na Hyung; Shim, Jae Kwang; Choi, Yong Sun; An, Seung Ho

2011-01-01

Background An appropriate level of sedation and pharmacological assist are essential during percutaneous transluminal balloon angioplasty (PTA). Ketamine provides good analgesia while preserving airway patency, ventilation, and cardiovascular stability with an opioid sparing effect suggesting that it would be ideal in combination with remifentanil and midazolam in spontaneously breathing patients. We evaluated the effect of a small dose of ketamine added to midazolam and remifentanil on analgesia/sedation for PTA procedures. Methods Sixty-four patients receiving PTA were enrolled. The Control group received midazolam 1.0 mg i.v. and continuous infusion of remifentanil 0.05 µg/kg/min. The Ketamine group received, in addition, an intravenous bolus of 0.5 mg/kg ketamine. Patients' haemodynamic data were monitored before remifentanil infusion, 5 min after remifentanil infusion, at 1, 3, 5, 30 min after incision, and at admission to the recovery room. Verbal numerical rating scales (VNRS) and sedation [OAA/S (Observer's Assessment of Alertness/Sedation)] scores were also recorded. Results The VNRS values at 1, 3, and 5 min after incision and OAA/S scores at 5 min after remifentanil infusion, and 1, 3, and 5 min after incision were lower in the Ketamine group than in the Control group. In the Control group, the VNRS value at 1 min after incision significantly increased and OAA/S values at 3, 5, and 30 min after incision significantly decreased compared to baseline values, while there were no significant changes in the ketamine group. Conclusions A small dose of ketamine as an adjunct sedative to the combination of midazolam and remifentanil produced a better quality of sedation and analgesia than without ketamine and provided stable respiration without cardiopulmonary deterioration. PMID:22110884

Pre-emptive multimodal analgesia with tramadol and ketamine-lidocaine infusion for suppression of central sensitization in a dog model of ovariohysterectomy.

PubMed

Kaka, Ubedullah; Rahman, Nor-Alimah; Abubakar, Adamu Abdul; Goh, Yong Meng; Fakurazi, Sharida; Omar, Mohamed Ariff; Chen, Hui Cheng

2018-01-01

The effects of pre-emptive infusion of ketamine-lidocaine with tramadol on the suppression of central sensitization were investigated in a dog ovariohysterectomy model. Twelve dogs were randomly assigned to two groups: ketamine-lidocaine-tramadol (KLT) and tramadol (T) groups. Both groups received intravenous tramadol 4 mg/kg body weight as premedication. Immediately after induction, the KLT group received ketamine and lidocaine at 0.5 and 2 mg/kg loading dose, followed by continuous rate infusion of 50 and 100 µg/kg/min, respectively, for 2 hours. Dogs in T group received saline bolus and continuous rate infusion at equi-volume. Intraoperatively, hemodynamic responses to surgical stimulation were recorded, whereas postoperative pain was evaluated using an algometer and short form of the Glasgow composite measure pain scale. Intraoperatively, hemodynamic responses to surgical stimulation were obtunded to a greater degree in KLT compared to T group. Postoperatively, the pain scores increased only for the first hour in KLT group, compared to 12 hours in T group. Mechanical thresholds at the abdomen decreased postoperatively between 12 and 60 hours in KLT group versus the entire 72 hours in T group. Thresholds at tibia and radius in both groups increased in the immediate 1 hour postoperatively, but decreased thereafter. Significant decrement of thresholds from baseline were detected in the tibia at 24, 42, and 60 hours in KLT group compared to 24-72 hours in T group, and in the radius between 36 and 48 hours in T group, but none in KLT group. Addition of pre-emptive ketamine-lidocaine infusion to single intravenous dose of tramadol enhanced attenuation of central sensitization and improved intra- and postoperative analgesia.

Low-Dose Ketamine Infusion for Adjunct Management during Vaso-occlusive Episodes in Adults with Sickle Cell Disease: A Case Series.

PubMed

Palm, Nicole; Floroff, Catherine; Hassig, Tanna B; Boylan, Alice; Kanter, Julie

2018-05-23

The optimal management of recurrent painful episodes in individuals living with sickle cell disease (SCD) remains unclear. Currently, the primary treatment for these episodes remains supportive, using fluids and intravenous opioid and anti-inflammatory medications. Few reports have described the use of adjunct subanesthetic doses of ketamine to opioids for treatment of refractory pain in SCD. This article reports a retrospective case series of five patients admitted to the intensive care unit (ICU) with prolonged vaso-occlusive episodes (VOEs). Patients were treated with a continuous-infusion of low-dose ketamine (up to 5 µg/kg/min) after insufficient pain control with opioid analgesic therapy. Outcomes studied included impact on opioid analgesic use, a description of ketamine dosing strategy, and an analysis of adverse events due to opioid or ketamine analgesia. Descriptive statistics are provided. During ketamine infusion, patients experienced a lower reported pain score (mean numeric rating scale [NRS] score 7.2 vs. 6.4), reduced opioid-induced adverse effects, and decreased opioid dosing requirements (median reduction of 90 mg morphine equivalents per patient). The average duration of severe pain during admission prior to ketamine therapy was 8 days. Only one of five patients reported an adverse effect (vivid dreams) secondary to ketamine infusion. The Richmond Agitation Sedation Scale (RASS) was assessed throughout therapy, with only one patient experiencing light drowsiness. Low-dose ketamine infusion may be considered as an adjunct analgesic agent in patients with vaso-occlusive episodes who report continued severe pain despite high-dose opioid therapy, particularly those experiencing opioid-induced adverse effects.

In Vivo MR Imaging of Pulmonary Perfusion and Gas Exchange in Rats via Continuous Extracorporeal Infusion of Hyperpolarized 129Xe

PubMed Central

Cleveland, Zackary I.; Möller, Harald E.; Hedlund, Laurence W.; Nouls, John C.; Freeman, Matthew S.; Qi, Yi; Driehuys, Bastiaan

2012-01-01

Background Hyperpolarized (HP) 129Xe magnetic resonance imaging (MRI) permits high resolution, regional visualization of pulmonary ventilation. Additionally, its reasonably high solubility (>10%) and large chemical shift range (>200 ppm) in tissues allow HP 129Xe to serve as a regional probe of pulmonary perfusion and gas transport, when introduced directly into the vasculature. In earlier work, vascular delivery was accomplished in rats by first dissolving HP 129Xe in a biologically compatible carrier solution, injecting the solution into the vasculature, and then detecting HP 129Xe as it emerged into the alveolar airspaces. Although easily implemented, this approach was constrained by the tolerable injection volume and the duration of the HP 129Xe signal. Methods and Principal Findings Here, we overcome the volume and temporal constraints imposed by injection, by using hydrophobic, microporous, gas-exchange membranes to directly and continuously infuse 129Xe into the arterial blood of live rats with an extracorporeal (EC) circuit. The resulting gas-phase 129Xe signal is sufficient to generate diffusive gas exchange- and pulmonary perfusion-dependent, 3D MR images with a nominal resolution of 2×2×2 mm3. We also show that the 129Xe signal dynamics during EC infusion are well described by an analytical model that incorporates both mass transport into the blood and longitudinal relaxation. Conclusions Extracorporeal infusion of HP 129Xe enables rapid, 3D MR imaging of rat lungs and, when combined with ventilation imaging, will permit spatially resolved studies of the ventilation-perfusion ratio in small animals. Moreover, EC infusion should allow 129Xe to be delivered elsewhere in the body and make possible functional and molecular imaging approaches that are currently not feasible using inhaled HP 129Xe. PMID:22363613

Efficient Permeability Measurement and Numerical Simulation of the Resin Flow in Low Permeability Preform Fabricated by Automated Dry Fiber Placement

NASA Astrophysics Data System (ADS)

Agogue, Romain; Chebil, Naziha; Deleglise-Lagardere, Mylène; Beauchene, Pierre; Park, Chung Hae

2017-10-01

We propose a new experimental method using a Hassler cell and air injection to measure the permeability of fiber preform while avoiding a race tracking effect. This method was proven to be particularly efficient to measure very low through-thickness permeability of preform fabricated by automated dry fiber placement. To validate the reliability of the permeability measurement, the experiments of viscous liquid infusion into the preform with or without a distribution medium were performed. The experimental data of flow front advancement was compared with the numerical simulation result using the permeability values obtained by the Hassler cell permeability measurement set-up as well as by the liquid infusion experiments. To address the computational cost issue, the model for the equivalent permeability of distribution medium was employed in the numerical simulation of liquid flow. The new concept using air injection and Hassler cell for the fiber preform permeability measurement was shown to be reliable and efficient.

Growth responses in a mutant dwarf rat to human growth hormone and recombinant human insulin-like growth factor I.

PubMed

Skottner, A; Clark, R G; Fryklund, L; Robinson, I C

1989-05-01

A new mutant GH-deficient dwarf rat has been used to study the effects of iv infusions of human GH (hGH) and recombinant human insulin-like growth factor I (hIGF-I). This animal has only about 5% of normal pituitary GH content, low circulating GH levels, and no regular GH surges. The defect seems to be specific for GH. Infusions of hIGF-I at 180 micrograms/day for 9 days elevated serum IGF-I concentrations significantly over those in the saline-infused controls (713 +/- 20 ng/ml vs. 395 +/- 31 ng/ml); hGH infusions did not raise IGF-I levels significantly (435 +/- 20 ng/ml). Gel filtration of serum samples showed that the high-dose hIGF-I infusions increased free IGF concentrations, without apparently altering the pattern of IGF-I binding whereas hGH infusions increased the amount of high mol wt IGF-I binding protein. Neither IGF-I nor hGH infusions affected the small amounts of rat GH present in the dwarf rat pituitary glands. Continuous iv infusions of hGH (200 mU/day for 9 days) stimulated body wt gain (2.1 +/- 0.2 g/day) and bone growth (96 +/- 9 microns/day) significantly compared to saline-infused dwarf rats (1.2 +/- 0.3 g/day and 43 +/- 3 microns/day). Infusions of hIGF-I at 180 micrograms/day produced a body wt gain (2.1 +/- 0.5 g/day) similar to that seen in the hGH-infused group but a significantly smaller stimulation of bone growth (63 +/- 3 microns/day). Infusion of a 5-fold lower dose of hIGF-I (36 micrograms/day for 9 days) had no effect on body wt or bone growth. Food intake was unaffected by either hGH or hIGF-I infusions. The pattern of tissue growth was affected differentially by hGH and IGF-I infusions that produced the same overall body wt gain. hGH induced a relatively proportional growth in most of the organs studied, whereas hIGF-I infusion at 180 micrograms/day stimulated a disproportionately greater growth of the kidney, adrenals, and spleen. In some of the animals, tissues were extracted for RIA of IGF-I; the amounts of IGF-I in the liver were similar in control, hGH, or IGF-I-infused animals, whereas kidney and adrenals from IGF-I infused animals contained larger amounts of immunoreactive IGF-I than did those tissues from hGH-treated rats. Thus, both hGH and hIGF-I can promote growth in the mutant dwarf rat, but they differ both quantitatively and qualitatively in their pattern of actions.

Cyclic ethanol metabolism in hypophysectomized rats continuously infused alcohol-containing diets

USDA-ARS?s Scientific Manuscript database

Chronic ethanol (EtOH) intake induces hepatic alcohol dehydrogenase (ADH) expression via disruption of insulin signaling in liver (JBC 2006; 281:1126-34). Total enteral nutrition (TEN) is a method of slow and continuous (approx. 23/day) feeding patients through an intragastric tube. Rats fed EtOH-co...

Leucine pulses enhance skeletal muscle protein synthesis during continuous feeding in neonatal pigs

USDA-ARS?s Scientific Manuscript database

Infants unable to maintain oral feeding can be nourished by orogastric tube. We have shown that orogastric continuous feeding restricts muscle protein synthesis compared with intermittent bolus feeding in neonatal pigs. To determine whether leucine leu infusion can be used to enhance protein synthes...

Immediate effects of different schedules of somatostatin on portal pressure in patients with liver cirrhosis.

PubMed

Zhang, C; Xu, J-M; Kong, D-R; Min, X-K; Chen, R

2013-06-01

Somatostatin (SST) is used for the treatment of acute variceal bleeding based on its ability to decrease portal pressure and collateral blood flow. To date, no studies have focused on the immediate-early effects (between 1 and 30 min) of SST. The aim of this study was to compare the efficacy of different schedules of SST therapy with placebo on portal pressure in patients with portal hypertension treated with portal-azygous disconnection and to test whether an increase in bolus or infusion dose can improve the clinical efficacy of SST therapy.   Patients were treated with four different schedules: (a) standard dose (n = 11): one 250 μg bolus + a continuous infusion of 250 μg/h; (b) medium dose (n = 10): 500 μg bolus + a continuous infusion of 250 μg/h; (c) high dose (n = 10): 250 μg bolus + a continuous infusion of 500 μg/h; (d) control (n = 10): an injection of placebo (saline) followed by a placebo infusion. Following SST or placebo administration, portal pressure, central venous pressure (CVP), systemic blood pressure and heart rate (HR) were measured at 1, 3, 5, 7, 10 and 30 min.   The three schedules of SST induced a marked, rapid and highly significant decrease in portal pressure. The decline in portal pressure was moderate at 1 min (P < 0·040), achieved a peak effect at 5 min (P < 0·009) and remained decreased at 30 min. The effect of SST on portal pressure was significantly greater than placebo from 1 min after administration. There were no significant differences in portal pressure decrease between the three schedules of SST. The three schedules of SST and the placebo schedule did not induce significant changes in HR, systemic blood pressure and CVP.   This study shows that SST is effective in decreasing portal pressure within 30 min of administration in patients with liver cirrhosis. The clinical schedule used in this study was reasonable and safe. © 2013 Blackwell Publishing Ltd.

Transient bradycardia induced by thiopentone sodium: a unique challenge in the management of refractory status epilepticus

PubMed Central

Sharma, Sushma; Nair, Pradeep P; Murgai, Aditya; Selvaraj, Raja J

2013-01-01

Thiopentone sodium is one of the important drugs in the armamentarium for terminating refractory status epilepticus, a neurological emergency. We report a case of thiopentone-related bradycardia during the management of the new onset refractory status epilepticus in a young man, which was circumvented by prophylactic insertion of temporary pacemaker while thiopentone infusion was continued. A systematic approach was employed to manage the status epilepticus, including infusion of thiamine and glucose followed by antiepileptic drugs. The patient was ventilated and infused with lorazepam, phenytoin, sodium valproate, levetiracetam and midazolam followed by thiopentone sodium. With the introduction of thiopentone the seizures could be controlled but the patient developed severe bradycardia and junctional rhythm. The bradycardia disappeared when thiopentone was withdrawn and reappeared when the drug was reintroduced. Propofol infusion was tried with no respite in seizures. Later thiopentone sodium was reintroduced after inserting temporary cardiac pacemaker. Seizure was controlled and patient was weaned off the ventilator. PMID:24130206

Transient bradycardia induced by thiopentone sodium: a unique challenge in the management of refractory status epilepticus.

PubMed

Sharma, Sushma; Nair, Pradeep P; Murgai, Aditya; Selvaraj, Raja J

2013-10-15

Thiopentone sodium is one of the important drugs in the armamentarium for terminating refractory status epilepticus, a neurological emergency. We report a case of thiopentone-related bradycardia during the management of the new onset refractory status epilepticus in a young man, which was circumvented by prophylactic insertion of temporary pacemaker while thiopentone infusion was continued. A systematic approach was employed to manage the status epilepticus, including infusion of thiamine and glucose followed by antiepileptic drugs. The patient was ventilated and infused with lorazepam, phenytoin, sodium valproate, levetiracetam and midazolam followed by thiopentone sodium. With the introduction of thiopentone the seizures could be controlled but the patient developed severe bradycardia and junctional rhythm. The bradycardia disappeared when thiopentone was withdrawn and reappeared when the drug was reintroduced. Propofol infusion was tried with no respite in seizures. Later thiopentone sodium was reintroduced after inserting temporary cardiac pacemaker. Seizure was controlled and patient was weaned off the ventilator.

Fluctuating functions related to quality of life in advanced Parkinson disease: effects of duodenal levodopa infusion.

PubMed

Isacson, D; Bingefors, K; Kristiansen, I S; Nyholm, D

2008-12-01

To assess fluctuations in quality of life (QoL) and motor performance in patients with advanced Parkinson disease (PD) treated with continuous daytime duodenal levodopa/carbidopa infusion or conventional therapy. Of 18 patients completing a 6-week trial (DIREQT), 12 were followed for up to 6 months and assessed using electronic diaries and the PD Questionnaire-39 (PDQ-39). During the trial and follow-up, major diurnal fluctuations were observed, especially for hyperkinesia, 'off' time, ability to walk and depression. Duodenal infusion was associated with significantly more favourable outcomes compared with conventional treatment for satisfaction with overall functioning, 'off' time and ability to walk, with improved outcomes with PDQ-39. Relative to conventional treatment, infusion therapy may stabilize and significantly improve motor function and patient's QoL. The potential for daily fluctuation in PD symptoms means single measures of treatment effectiveness can result in bias in effect estimates and hence repeated measures are recommended.

Control of cancer pain by epidural infusion of morphine.

PubMed

Waterman, N G; Hughes, S; Foster, W S

1991-10-01

Pain that cannot be controlled by traditional oral and parenteral methods in those patients with advanced cancer can be alleviated by spinal administration of narcotics. Epidural and intrathecal infusion with morphine causes analgesia by blocking spinal receptors without significant long-term central nervous, gastrointestinal, and genitourinary system effects. Of the total of 33 patients, epidural catheters inserted in 20 patients then connected by a subcutaneous tunnel to a continuous infusion system. Implanted pumps were used in each of these patients. Because of the cost and limitations of the implanted pumps, epidural catheters were connected, either directly or by subcutaneous reservoirs, to external ambulatory infusion pumps in the remaining 13 patients. Patient assessment by a linear analogue scale to measure pain levels determined that 23 of the 33 total patients (70%) had excellent or good relief of pain. The delivery of spinal administration of narcotics to treat intractable cancer pain in patients is safe. Most importantly, this method of delivery can be used in community hospitals, in outpatient settings, and in home health care programs.

The effect of dexmedetomidine continuous infusion as an adjuvant to general anesthesia on sevoflurane requirements: A study based on entropy analysis

PubMed Central

Patel, Chirag Ramanlal; Engineer, Smita R; Shah, Bharat J; Madhu, S

2013-01-01

Background: Dexmedetomidine, a α2 agonist as an adjuvant in general anesthesia, has anesthetic and analgesic-sparing property. Aims: To evaluate the effect of continuous infusion of dexmedetomidine alone, without use of opioids, on requirement of sevoflurane during general anesthesia with continuous monitoring of depth of anesthesia by entropy analysis. Materials and Methods: Sixty patients were randomly divided into 2 groups of 30 each. In group A, fentanyl 2 mcg/kg was given while in group B, dexmedetomidine was given intravenously as loading dose of 1 mcg/kg over 10 min prior to induction. After induction with thiopentone in group B, dexmedetomidine was given as infusion at a dose of 0.2-0.8 mcg/kg. Sevoflurane was used as inhalation agent in both groups. Hemodynamic variables, sevoflurane inspired fraction (FIsevo), sevoflurane expired fraction (ETsevo), and entropy (Response entropy and state entropy) were continuously recorded. Statistical analysis was done by unpaired student's t-test and Chi-square test for continuous and categorical variables, respectively. A P-value < 0.05 was considered significant. Results: The use of dexmedetomidine with sevoflurane was associated with a statistical significant decrease in ETsevo at 5 minutes post-intubation (1.49 ± 0.11) and 60 minutes post-intubation (1.11 ±0.28) as compared to the group A [1.73 ±0.30 (5 minutes); 1.68 ±0.50 (60 minutes)]. There was an average 21.5% decrease in ETsevo in group B as compared to group A. Conclusions: Dexmedetomidine, as an adjuvant in general anesthesia, decreases requirement of sevoflurane for maintaining adequate depth of anesthesia. PMID:24106354

Continuous-infusion local anesthetic pain pump use and seroma formation with abdominal procedures: is there a correlation?

PubMed

Smith, Melissa M; Hovsepian, Raffi V; Markarian, Mark K; Degelia, Amber L; Paul, Malcolm D; Evans, Gregory R D; Wirth, Garrett A

2008-11-01

Seroma formation is the most commonly occurring complication in plastic surgery abdominal procedures. Continuous local anesthetic pain pump delivery systems are often used to decrease postoperative pain. An unreported concern with use of these devices in abdominal procedures is the effect of continuous fluid infiltration of the surgical site and a possible increase in the incidence of seroma formation. The authors performed a retrospective chart review to evaluate all patients (n = 159) who underwent abdominal procedures (abdominoplasty, panniculectomy, and transverse rectus abdominis myocutaneous flap harvest) over a 3-year period. Patient charts were evaluated for sex, age, body mass index, procedure performed, surgeon, operation length, pain pump use, postoperative seroma formation, and any complications. In cases with pain pump use, catheter placement location, anesthetic medication and strength, continuous-infusion rate, and duration of pain pump use were also reviewed. If a postoperative seroma formation was identified, treatment and outcomes were also recorded. The overall seroma formation rate was 11.3 percent (18 of 159 patients). Other complications occurred at a rate of 2.5 percent (four of 159). The incidence of seroma was 11.0 percent (11 of 100) in patients with pain pump use versus 11.9 percent (7 of 59) in those who did not use a pain pump. There was no statistically significant difference (p = 0.9) in the incidence of seroma formation between those who did and did not use a pain pump device. There was no correlation between increased rate of seroma formation and use of a continuous-infusion local anesthetic pain pump system in our patient population.

Plasma concentrations of fentanyl with subcutaneous infusion in palliative care patients.

PubMed

Miller, R S; Peterson, G M; Abbott, F; Maddocks, I; Parker, D; McLean, S

1995-12-01

1. Plasma concentrations of fentanyl were measured by g.c. in 20 patients (median age: 75 years and range: 54-86 years; eight females) in palliative care receiving the drug by continuous s.c. infusion (median rate: 1200 micrograms day-1 and range: 100-5000 micrograms day-1). 2. The infusion rate was significantly related to the duration of therapy (Spearman rho = 0.56, P < 0.05). The total steady-state plasma concentrations of fentanyl ranged between 0.1 and 9 ng ml-1, with a median of 1 ng ml-1. The unbound fraction of fentanyl in the plasma ranged from 17.8 to 44.4%, with a median value of 33.6%. Infusion rates and both total and unbound plasma concentrations of fentanyl were correlated (Spearman rho = 0.92, P < 0.05 in each case). Even with standardization for dosage, there was an eightfold variation in total plasma concentrations and 3.5-fold variation in unbound plasma concentrations of fentanyl. 3. There is considerable inter-patient variability in the pharmacokinetics of fentanyl with s.c. infusion in the palliative care setting, which necessitates careful titration of dosage according to individual clinical response.

[Methods of preventing phlebitis induced by infusion of fosaprepitant].

PubMed

Kohno, Emiko; Kanematsu, Sayaka; Okazaki, Satoshi; Ogata, Makoto; Kanemitsu, Meiko; Yamashita, Hiromi; Syuntou, Kaori; Sekita, Masako; Nishioka, Ryoko; Yoshida, Hideyuki

2015-03-01

At our hospital, we use aprepitant for nausea and vomiting when administering highly emetic anticancer agents, according to "Guidelines for the Appropriate Use of Antiemetic Agents" given by the Japan Society of Clinical Oncology. We initiated the intravenous administration of fosaprepitant for better compliance compared with aprepitant; however, we observed phlebitis after the infusion of fosaprepitant. Therefore, we investigated measures to reduce phlebitis associated with the infusion of fosaprepitant. For the first premedication, fosaprepitant (150 mg) was dissolved in 100 mL of saline and administered for 30 minutes; 1 of 2 patients showed grade 4 phlebitis. For the modified premedication, fosaprepitant, dexamethasone, and 5- HT(3) antagonist were dissolved in 100 mL of saline and administered for 30 minutes. The modified premedication was administered to a total of 27 patients; 5 patients developed mild phlebitis (grade 1), but infusion could be continued by treating their phlebitis with a hot pack. We used a combination of dexamethasone and 5-HT(3) antagonist with fosaprepitant as a modified premedication in order to avoid drug-induced vascular damage, which resulted in the pH decreasing to 6.20-7.55 (close to neutral) and a shorter infusion time.

Striatal Infusion of Glial Conditioned Medium Diminishes Huntingtin Pathology in R6/1 Mice

PubMed Central

Perucho, Juan; Casarejos, Maria José; Gómez, Ana; Ruíz, Carolina; Fernández-Estevez, Maria Ángeles; Muñoz, Maria Paz; de Yébenes, Justo García; Mena, Maria Ángeles

2013-01-01

Huntington's disease is a neurodegenerative disorder caused by an expansion of CAG repeats in the huntingtin gene which produces widespread neuronal and glial pathology. We here investigated the possible therapeutic role of glia or glial products in Huntington's disease using striatal glial conditioned medium (GCM) from fetus mice (E16) continuously infused for 15 and 30 days with osmotic minipumps into the left striatum of R6/1 mice. Animals infused with GCM had significantly less huntingtin inclusions in the ipsilateral cerebral cortex and in the ipsilateral and contralateral striata than mice infused with cerebrospinal fluid. The numbers of DARPP-32 and TH positive neurons were also greater in the ipsilateral but not contralateral striata and substantia nigra, respectively, suggesting a neuroprotective effect of GCM on efferent striatal and nigro-striatal dopamine neurons. GCM increases activity of the autophagic pathway, as shown by the reduction of autophagic substrate, p-62, and the augmentation of LC3 II, Beclin-1 and LAMP-2 protein levels, direct markers of autophagy, in GCM infused mice. GCM also increases BDNF levels. These results suggest that CGM should be further explored as a putative neuroprotective agent in Huntington's disease. PMID:24069174

Antibody-containing cell response in lymph of sheep after intra-intestinal infusion of ovalbumin with and without DEAE-dextran.

PubMed Central

Beh, K J

1979-01-01

The output of antibody-containing cells (ACC) was monitored in efferent ileal lymph after continuous infusion of ovalbumin into the ileum of sheep with and without the adjuvant DEAE-dextran. When ovalbumin was infused at the slow rate of 5 ml/h, maximum outputs of 2.9 x 10(5) and 2.4 x 10(5 ACC/h were observed on days 9 and 16 respectively. When infused at the faster rate of 15 ml/h, peak levels of 6.9 x 10(5) and 11.7 x 10(5) ACC/h were recorded on days 10 and 16 respectively. The maximum response was substantially enhanced when ovalbumin was infused simultaneously with DEAE-dextran when a mean output of 51.7 x 10(5) ACC/h occurred on day 10. With all treatments the distribution of ACC amongst various immunoglobulin classes was similar. During the first few days of the response IgM-specific ACC predominated and later IgG1-specific ACC were most abundant. Throughout the response a substantial proportion (10-81%) of ACC in efferent ileal lymph were IgA-specific. PMID:572818

Infusion dose requirement of rocuronium in patients on phenytoin therapy - A prospective comparative study.

PubMed

Sheshadri, Veena; Radhakrishnan, Arathi; Halemani, Kusuma; Keshavan, Venkatesh H

2017-10-01

Patients with intracranial tumour are usually on anticonvulsants. Patients on phenytoin therapy demonstrate rapid metabolism of nondepolarising muscle relaxants secondary to enzyme induction. Infusion dose requirement of rocuronium in such patients has been sparingly studied. We studied the continuous infusion dose requirement of rocuronium bromide in patients on phenytoin therapy and its correlation with serum levels of phenytoin. Seventy-five patients scheduled for supratentorial tumour surgery were included in the study. Patients not on phenytoin were taken as control. The primary outcome variable studied was the infusion dose requirement of rocuronium in patients on phenytoin. Based on pre-operative serum phenytoin levels, study group patients were divided into two groups: sub-therapeutic level group (phenytoin level <10 μg/mL) and therapeutic level group (phenytoin level >10 μg/mL). Following anaesthesia induction, rocuronium bromide 0.6 mg/kg was administered to achieve tracheal intubation. Rocuronium infusion was titrated to maintain zero response on the train-of-four response. Demographic data were comparable. Patients receiving phenytoin required higher infusion dose compared to the control group (0.429 ± 0.2 mg/kg/h vs. 0.265 ± 0.15 mg/kg/h, P < 0.001). The serum phenytoin level had no correlation to infusion dose requirement of rocuronium (0.429 ± 0.205 mg/kg/h vs. 0.429 ± 0.265 mg/kg/h ( P = 0.815). The recovery was faster in the phenytoin group compared to the control group. Haowever, it was not clinically significant. The infusion dose requirement of rocuronium bromide in patients on phenytoin is higher and the serum levels of phenytoin does not influence the dose required.

Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn's disease: a randomized controlled trial.

PubMed

Farrell, Richard J; Alsahli, Mazen; Jeen, Yoon-Tae; Falchuk, Kenneth R; Peppercorn, Mark A; Michetti, Pierre

2003-04-01

We assessed the relationship between antibodies to infliximab (ATI) and the loss of response postinfliximab, infusion reactions and, in a randomized trial, investigated whether intravenous hydrocortisone premedication can reduce ATI. Initially, we prospectively evaluated clinical response, adverse events, and ATI levels in 53 consecutive patients with Crohn's disease who received 199 infliximab (5 mg/kg) infusions. Subsequently, 80 patients with Crohn's disease were randomized to intravenous hydrocortisone 200 mg or placebo immediately before their first and subsequent infliximab infusions. The primary endpoint was reduction in median ATI levels at week 16. Analysis was by intention to treat. Nineteen of our initial 53 patients (36%) developed ATI, including all 7 patients with serious infusion reactions (median ATI level, 19.6 microg/mL). Eleven of 15 patients (73%) who lost their initial response were ATI positive compared with none of 21 continuous responders, (8.9 vs. 0.7 microg/mL, P < 0.0001). Administering a second infusion within 8 weeks of the first (OR, 0.13; 95% CI, 0.03-0.5; P = 0.0007) or concurrent immunosuppressants (OR, 0.19; 95% CI, 0.04-1.03; P = 0.007) significantly reduced ATI formation. In the placebo-controlled trial, ATI levels were lower at week 16 among hydrocortisone-treated patients (1.6 vs. 3.4 microg/mL, P = 0.02), and 26% of hydrocortisone-treated patients developed ATI compared with 42% of placebo-treated patients, P = 0.06. Loss of initial response and infusion reactions post-infliximab is strongly related to ATI formation and level. Administering a second infusion within 8 weeks of the first and concurrent immunosuppressant therapy significantly reduce ATI formation. Intravenous hydrocortisone premedication significantly reduces ATI levels but does not eliminate ATI formation or infusion reactions.

Epidural Baclofen for the Management of Postoperative Pain in Children With Cerebral Palsy.

PubMed

Nemeth, Blaise A; Montero, Robert J; Halanski, Matthew A; Noonan, Kenneth J

2015-09-01

Children with cerebral palsy undergoing soft tissue and bony procedures often experience pain and spasticity postoperatively. Differentiation of pain from spasticity complicates management, so controlling spasticity with a continuous infusion of baclofen, an antispasmodic, through an already present indwelling epidural catheter holds interest. A retrospective chart review was performed of patients with cerebral palsy undergoing single event, multilevel lower extremity surgery at a single institution who received epidural analgesia with or without continuous baclofen infusion. Primary outcomes included need for supplemental narcotic analgesics and benzodiazepines postoperatively. Duration of hospitalization, pain scores, and complications were also evaluated. Forty-four patients were identified, ranging in age from 3 to 17 years, 19 of whom received epidural baclofen. No differences were found in use of supplemental narcotic analgesia, benzodiazepines, or duration of hospitalization. Differences in pain scores were not statistically significant (0.82±0.95 for baclofen vs. 1.48±0.99 for controls) (P=0.391). Mean arterial pressure was lower in patients receiving baclofen (P=0.004). No potential side effects attributable to baclofen were noted. Continuous epidural baclofen infusion seems unlikely to alter the pain-spasm cycle experienced by patients with cerebral palsy following orthopaedic surgery to a clinically significant degree. More effective, and cost-effective, measures at assessing and controlling pain and muscle spasm should be explored to benefit cerebral palsy patients postoperatively. Level III-therapeutic study.

Continuous quality improvement using intelligent infusion pump data analysis.

PubMed

Breland, Burnis D

2010-09-01

The use of continuous quality-improvement (CQI) processes in the implementation of intelligent infusion pumps in a community teaching hospital is described. After the decision was made to implement intelligent i.v. infusion pumps in a 413-bed, community teaching hospital, drug libraries for use in the safety software had to be created. Before drug libraries could be created, it was necessary to determine the epidemiology of medication use in various clinical care areas. Standardization of medication administration was performed through the CQI process, using practical knowledge of clinicians at the bedside and evidence-based drug safety parameters in the scientific literature. Post-implementation, CQI allowed refinement of clinically important safety limits while minimizing inappropriate, meaningless soft limit alerts on a few select agents. Assigning individual clinical care areas (CCAs) to individual patient care units facilitated customization of drug libraries and identification of specific CCA compliance concerns. Between June 2007 and June 2008, there were seven library updates. These involved drug additions and deletions, customization of individual CCAs, and alterations of limits. Overall compliance with safety software use rose over time, from 33% in November 2006 to over 98% in December 2009. Many potentially clinically significant dosing errors were intercepted by the safety software, prompting edits by end users. Only 4-6% of soft limit alerts resulted in edits. Compliance rates for use of infusion pump safety software varied among CCAs over time. Education, auditing, and refinement of drug libraries led to improved compliance in most CCAs.

Efficacy of primed infusions with high dose ranitidine and omeprazole to maintain high intragastric pH in patients with peptic ulcer bleeding: a prospective randomised controlled study.

PubMed Central

Labenz, J; Peitz, U; Leusing, C; Tillenburg, B; Blum, A L; Börsch, G

1997-01-01

BACKGROUND: In healthy subjects, continuous infusions of high dose ranitidine and omeprazole produce high intragastric pH values. AIM: To test the hypothesis that both drugs also maintain high intragastric pH values in patients with bleeding ulcers. PATIENTS AND METHODS: In two parallel studies, 20 patients with bleeding duodenal ulcers and 20 patients with bleeding gastric ulcers were randomly assigned to receive either ranitidine (0.25 mg/kg/hour after a bolus of 50 mg) or omeprazole (8 mg/hour after a bolus of 80 mg) for 24 hours. Intragastric pH was continuously recorded with a glass electrode placed 5 cm below the cardia. RESULTS: Both drugs rapidly raised the intragastric pH above 6. During the second 12 hour period, however, the percentage of time spent below a pH of 6 was 0.15% with omeprazole and 20.1% with ranitidine (p = 0.0015) in patients with duodenal ulcer; in patients with gastric ulcer it was 0.1% with omeprazole and 46.1% with ranitidine (p = 0.002). CONCLUSIONS: Primed infusions of omeprazole after a bolus produced consistently high intragastric pH values in patients with bleeding peptic ulcers, whereas primed infusions with ranitidine were less effective during the second half of a 24 hour treatment course. This loss of effectiveness may be due to tolerance. PMID:9155573

Air Pump-Assisted Graft Centration, Graft Edge Unfolding, and Graft Uncreasing in Young Donor Graft Pre-Descemet Endothelial Keratoplasty.

PubMed

Jacob, Soosan; Narasimhan, Smita; Agarwal, Amar; Agarwal, Athiya; A I, Saijimol

2017-08-01

To assess an air pump-assisted technique for graft centration, graft edge unfolding, and graft uncreasing while performing pre-Descemet endothelial keratoplasty (PDEK) using young donor grafts. Continuous pressurized air infusion was used for graft centration, graft edge unfolding, and graft unwrinkling. Ten eyes of 10 patients underwent PDEK with donors aged below 40 years. In all eyes, the donor scrolled into tight scrolls. In all cases, the air pump-assisted technique was effective in positioning and centering the graft accurately and in straightening infolded graft edges and smoothing out graft creases and wrinkles. Endothelial cell loss was 38.6%. Postoperative best-corrected visual acuity at 6 months was 0.66 ± 0.25 in decimal equivalent. Continuous pressurized air infusion acted as a third hand providing a continuous pressure head that supported the graft and prevented graft dislocation as well as anterior chamber collapse during intraocular maneuvering. Adequate maneuvering space was available in all cases, and bleeding, if any, was tamponaded successfully in all cases. Although very young donor grafts may be used for PDEK, they are difficult to center and unroll completely before floating against host stroma. An air pump-assisted technique using continuous pressurized air infusion allows successful final graft positioning even with very young donor corneas. It thus makes surgery easier as several key steps are made easier to handle. It additionally helps in tamponading hemorrhage during peripheral iridectomy, increasing surgical space, preventing fluctuations in the anterior chamber depth, and promoting graft adherence.

Time-Dependent Compensatory Responses to Chronic Neuroinflammation in Hippocampus and Brainstem: The Potential Role of Glutamate Neurotransmission

PubMed Central

Brothers, Holly M.; Bardou, Isabelle; Hopp, Sarah C.; Marchalant, Yannick; Kaercher, Roxanne M.; Turner, Sarah M.; Mitchem, Mollie R.; Kigerl, Kristina; Wenk, Gary L.

2014-01-01

Chronic neuroinflammation is characteristic of neurodegenerative diseases and is present during very early stages, yet significant pathology and behavioral deficits do not manifest until advanced age. We investigated the consequences of experimentally-induced chronic neuroinflammation within the hippocampus and brainstem of young (4 mo) F-344 rats. Lipopolysaccharide (LPS) was infused continuously into the IVth ventricle for 2, 4 or 8 weeks. The number of MHC II immunoreactive microglia in the brain continued to increase throughout the infusion period. In contrast, performance in the Morris water maze was impaired after 4 weeks but recovered by 8 weeks. Likewise, a transient loss of tyrosine hydroxylase immunoreactivity in the substantia nigra and locus coeruleus was observed after 2 weeks, but returned to control levels by 4 weeks of continuous LPS infusion. These data suggest that direct activation of microglia is sufficient to drive, but not sustain, spatial memory impairment and a decrease in tyrosine hydroxylase production in young rats. Our previous studies suggest that chronic neuroinflammation elevates extracellular glutamate and that this elevation underlies the spatial memory impairment. In the current study, increased levels of GLT1 and SNAP25 in the hippocampus corresponded with the resolution of performance deficit. Increased expression of SNAP25 is consistent with reduced glutamate release from axonal terminals while increased GLT1 is consistent with enhanced clearance of extracellular glutamate. These data demonstrate the capacity of the brain to compensate for the presence of chronic neuroinflammation, despite continued activation of microglia, through changes in the regulation of the glutamatergic system. PMID:24600537

From Interactions to Conversations: The Development of Joint Engagement during Early Childhood

PubMed Central

Adamson, Lauren B.; Bakeman, Roger; Deckner, Deborah F.; Nelson, P. Brooke

2013-01-01

This research traces the development of symbol-infused joint engagement during mother-child interactions into the preschool years. Forty-nine children, who had been previously observed as toddlers (Adamson, Bakeman, & Deckner, 2004), were systematically observed during interactions with their mothers at ages 3½, 4½, and 5½ during activities related to the past and future, internal states, and graphic systems. Although the amount of symbol-infused joint engagement reached a ceiling by 3½, its focus continued to became more complex and its form more balanced. Individual differences in children’s symbol-infused joint engagement were stable across four years. These findings highlight both how joint engagement is transformed as conversational skills develop and how it remains rooted in earlier interactions and supported by caregiver’s actions. PMID:24266591

Suppression of Rabbit VX‐2 Subcutaneous Tumor Growth by Gadolinium Neutron Capture Therapy

PubMed Central

Tokita, Nobuhiko; Tokuuye, Koichi; Satoh, Michinao; Churei, Hisahiko; Pechoux, Cécile Le; Kobayashi, Tooru; Kanda, Keiji

1993-01-01

VX‐2 tumors growing in hind legs of New Zealand White rabbits (n=4) were exposed to thermal neutrons for 40 min (2.1 × 1012 neutrons cm−2) while one of two hind leg tumors of each rabbit was infused continuously with meglumine gadopentetate through a branch of the left femoral artery. The contralateral (uninfused) tumors served as controls. Although no differential distribution of gadolinium was achieved between the tumor and its adjacent normal tissue, the gadolinium concentration in the infused tumor was approximately 5–6 fold higher than that in the contralateral tumor. Growth of gadolinium‐infused tumors was significantly inhibited compared to that of control tumors (P<0.05) between the 16th and 23rd days after treatment. PMID:8407547

Current and emerging therapies for Addison's disease.

PubMed

Napier, Catherine; Pearce, Simon H S

2014-06-01

The purpose of this article is to review the current therapy of Addison's disease and to highlight recent developments in this field. Conventional steroid replacement for Addison's disease consists of twice or three-times daily oral hydrocortisone and once-daily fludrocortisone; however, new treatment modalities such as modified-released hydrocortisone and continuous subcutaneous hydrocortisone infusion have recently been developed. These offer the potential for closer simulation of the physiological serum cortisol rhythm. Two studies have also looked at modifying the natural history of adrenal failure using adrenocorticotropic hormone (ACTH) stimulation and immunomodulatory therapies, leading to the concept of residual adrenal function in some Addison's disease patients. Following more than 60 years with no significant innovation in the management of Addison's disease, these new approaches hold promise for improved patient health and better quality of life in the future.

[Morphine-antiemetics mixtures for continuous subcutaneous infusion in terminal cancer].

PubMed

Ottesen, S; Monrad, L

1992-05-30

Simultaneous pain, nausea and vomiting are not uncommon in terminal suffering requiring treatment with various compounds of analgesics and antiemetics. At Baerum Hospital the pump reservoirs for continuous, subcutaneous drug delivery are routinely filled by the hospital pharmacist. We examined the physico-chemical stability of various concentrations of mixtures of morphine-metoclopramide and morphine-metoclopramide-haloperidol at 25 degrees C. We found good stability for at least seven days. Addition of haloperidol seems to reduce stability. Plain morphine-haloperidol solutions are unstable. Split products were not found in any of the mixtures. We also examined the osmolality of current clinical compounds, focusing on local irritant effect at the infusion site. All solutions except for one with a high concentration of haloperidol were found to be close to isoosmolarl.

Multimodal analgesia without parenteral narcotics for total knee arthroplasty.

PubMed

Dorr, Lawrence D; Raya, Julio; Long, William T; Boutary, Myriam; Sirianni, Leigh Ellen

2008-06-01

Use of parenteral narcotics after total knee arthroplasty is considered by most orthopedic surgeons to be the standard of care. This study tested the hypothesis that a multimodal oral pain medication protocol could control pain and minimize complications of parenteral narcotics. Postoperative oral analgesia was augmented with either continuous epidural infusion or continuous femoral infusion using ropivacaine only. Seventy patients had total knee arthroplasty with a protocol that included preemptive oral analgesics, epidural anesthesia, pericapsular analgesic injection, and postoperative analgesia without parenteral opioids. The average daily pain score was less than 4 out of 10, nausea occurred in 15 patients (21%), emesis in 1 patient (1.4%), and there were no severe complications. This study proved the hypothesis that pain after total knee arthroplasty could be effectively managed without routine use of parenteral opioids.

Jejunal Infusion of Glucose Decreases Energy Intake to a Greater Extent than Fructose in Adult Male Rats12

PubMed Central

Moghadam, Alexander A; Moran, Timothy H; Dailey, Megan J

2016-01-01

Background: Intestinal nutrient infusions result in variable decreases in energy intake and body weight based on nutrient type and specific intestinal infusion site. Objective: The objective was to test whether an intrajejunal fructose infusion (FRU) would lower energy intake and body weight and induce similar increases in gut hormones as those found after intrajejunal glucose infusions (GLU). Methods: Male Sprague-Dawley rats received an intrajejunal infusion of either an equal kilocalorie load of glucose or fructose (11.4 kcal) or saline (SAL) for 5 d while intake of a standard rodent diet was continuously recorded; body weight was measured daily. Immediately after the infusion on the final day, rats were killed and plasma was collected to measure hormones. Results: Daily energy intake was significantly lower in the GLU group than in the SAL group, but the FRU group did not differ from the GLU or SAL groups when the 11.4 kcal of the infusate was included as energy intake. Lower energy intake was due to smaller meal sizes during the infusion period in the GLU group than in the FRU and SAL groups; the FRU and SAL groups did not differ. The percentage of change in body weight was lower in the GLU group than in the FRU and SAL groups. Plasma glucagon-like-peptide 1 (GLP-1) concentrations were greater in the GLU group than in the SAL group; the FRU group did not differ from the GLU or SAL groups. The plasma insulin concentration was greater in the FRU group than in both the GLU and SAL groups. Conclusion: These results demonstrate that glucose induces a greater decrease in energy intake and increase in GLP-1 at distal intestinal sites than fructose in rats, which may explain differential effects of these monosaccharides between studies when delivered orally or along the proximal to distal axis of the intestine. PMID:27581579

The effect of hyperglycemic hyperinsulinemia on small-intestinal mucosal protein synthesis in patients after surgical stress.

PubMed

Rittler, Peter; Schiefer, Beatrice; Demmelmair, Hans; Koletzko, Berthold; Vogeser, Michael; Alpers, David H; Jauch, Karl-Walter; Hartl, Wolfgang H

2006-01-01

Hyperglycemic hyperinsulinemia cannot stimulate intestinal protein synthesis in healthy individuals but does so in conditions characterized by an altered somatotropic axis such as diabetes. Only in a state of growth hormone resistance (high growth hormone but low insulin like growth factor [IGF-1] concentrations), extra insulin may acutely reverse the impaired, growth-hormone-induced IGF-1 release, thereby exerting anabolic actions at the intestinal tract. Growth hormone resistance can be also found in patients after surgical stress. Therefore, we wanted to test the hypothesis whether hyperglycemic hyperinsulinemia would stimulate ileal protein synthesis in the latter condition. Mass spectrometry techniques (capillary gas chromatography/combustion isotope ratio mass spectrometry) were used to directly determine the incorporation rate of 1-[(13)C]-leucine into ileal mucosal protein. All subjects had an ileostomy, which allowed easy access to the ileal mucosa, and consecutive sampling from the same tissue was performed during continuous isotope infusion (0.16 mumol/kg min). Isotopic enrichments and fractional protein synthesis were determined at baseline (period I) and after a 4-hour glucose infusion (170 mg/kg/h) or after infusion of saline (control group) (period II). In controls, ileal protein synthesis declined significantly during prolonged isotope infusion (period I: 1.11 +/- 0.14%/h, period II: 0.39 +/- 0.13%/h, p < .01). In contrast, ileal protein synthesis remained constant during glucose infusion (period I: 1.32 +/- 0.35%/h, period II: 1.33 +/- 0.21%/h, n.s. vs period I, but p < .005 vs the corresponding value at the end of period II in the control group). Using the continuous tracer infusion technique, ileal protein synthesis seemingly declines over a short time in control subjects. We found evidence that this artificial decline was due to mass effects of a rapidly turning over mucosa protein pool in which an isotopic plateau was reached during the experiment and of which the size amounted to approximately 4% of the total mixed protein pool. Maintenance of ileal protein synthesis during glucose infusion therefore indicates a rise of ileal protein synthesis in a slowly turning over protein pool. This effect in postsurgical patients would be compatible with the concept of intestinal insulin action to depend on the specific clinical state (eg, growth hormone resistance).

Population pharmacokinetics of phenytoin after intravenous administration of fosphenytoin sodium in pediatric patients, adult patients, and healthy volunteers.

PubMed

Tanaka, Jun; Kasai, Hidefumi; Shimizu, Kenji; Shimasaki, Shigeki; Kumagai, Yuji

2013-03-01

We performed a population pharmacokinetic analysis of phenytoin after intravenous administration of fosphenytoin sodium in healthy, neurosurgical, and epileptic subjects, including pediatric patients, and determined the optimal dose and infusion rate for achieving the therapeutic range. We used pooled data obtained from two phase I studies and one phase III study performed in Japan. The population pharmacokinetic analysis was performed using NONMEM software. The optimal dose and infusion rate were determined using simulation results obtained using the final model. The therapeutic range for total plasma phenytoin concentration is 10-20 μg/mL. We used a linear two-compartment model with conversion of fosphenytoin to phenytoin. Pharmacokinetic parameters of phenytoin, such as total clearance and central and peripheral volume of distribution were influenced by body weight. The dose simulations are as follows. In adult patients, the optimal dose and infusion rate of phenytoin for achieving the therapeutic range was 22.5 mg/kg and 3 mg/kg/min respectively. In pediatric patients, the total plasma concentration of phenytoin was within the therapeutic range for a shorter duration than that in adult patients at 22.5 mg/kg (3 mg/kg/min). However, many pediatric patients showed phenytoin concentration within the toxic range after administration of a dose of 30 mg/kg. The pharmacokinetics of phenytoin after intravenous administration of fosphenytoin sodium could be described using a linear two-compartment model. The administration of fosphenytoin sodium 22.5 mg/kg at an infusion rate of 3 mg/kg/min was optimal for achieving the desired plasma phenytoin concentration.

Insulin pump therapy: what is the evidence for using different types of boluses for coverage of prandial insulin requirements?

PubMed

Heinemann, Lutz

2009-11-01

Bolus infusion of insulin along with a meal is a standard procedure with continuous subcutaneous insulin infusion. Modern insulin pumps allow applying this bolus in four different ways: infusion of the total dose at once or splitting the dose into two boluses, infusion of a part of the bolus in the usual manner plus infusion of the other part over a prolonged period of time (with a higher infusion rate than the basal rate), or infusion of the total dose in the form of an elevated basal rate. Depending on the composition of the given meal and its glycemic index, this is an attempt to match the circulating insulin levels to the rate of glucose absorption from the gut in order to minimize postprandial glycemic excursions. However, in the framework of evidence-based medicine, the benefits of this approach should be proven in appropriately designed clinical studies. Performance of meal-related studies requires careful attention to many aspects in order to allow meaningful evaluation of a given intervention (i.e., type of bolus). Critical evaluation of the clinical experimental studies and the one clinical study published about the impact of different types of boluses on postprandial metabolic control revealed fundamental shortcomings in study design and performance in these studies. Insufficient establishment of comparable preprandial glycemia and insulinemia on the different study days within and between the patients studied is one key aspect. Therefore, the recommendation made in most of these studies (i.e., use of dual-wave bolus) has to be accepted with care, until we have better evidence.

The properties of an improvised piston pump for the rapid delivery of intravenous fluids.

PubMed

Smart, C M; Primrose, C W; Peters, A L; Speirits, E J

2014-02-01

To maximise the effect of a small fluid load, it is occasionally desirable to bolus manually with multiple depressions of a large-capacity syringe. This is usually achieved by placing the syringe on the side port of a three-way tap. We modified this technique by placing two-one-way valves in line with the three-way tap, effectively creating a piston pump, the infusion rates via which we compared with those achieved by an inflatable pressure-infuser in a simulated resuscitation. Fluid flow was faster using the piston pump than with the pressure-infuser (mean (SD) time to infuse 2000 ml saline 0.9% via a 16-G cannula 352 (10) s vs 495 (19) s, respectively, p < 0.0001). The piston pump appears to have potential for both tight control of fluid delivery and major high-volume resuscitation. The lightweight nature of the pump and its lack of reliance on gravity may also make it suitable for the pre-hospital setting. © 2014 The Association of Anaesthetists of Great Britain and Ireland.

Recurrent Coagulopathy after Rattlesnake Bite Requiring Continuous Intravenous Dosing of Antivenom

PubMed Central

2015-01-01

Context. Snakebite envenomation is common and may result in systemic coagulopathy. Antivenom can correct resulting laboratory abnormalities; however, despite antivenom use, coagulopathy may recur, persist, or result in death after a latency period. Case Details. A 50-year-old previously healthy man presented to the emergency department after a rattlesnake bite to his right upper extremity. His presentation was complicated by significant glossal and oropharyngeal edema requiring emergent cricothyrotomy. His clinical course rapidly improved with the administration of snake antivenom (FabAV); the oropharyngeal and upper extremity edema resolved within several days. However, over the subsequent two weeks, he continued to have refractory coagulopathy requiring multiple units of antivenom. The coagulopathy finally resolved after starting a continuous antivenom infusion. Discussion. Envenomation may result in latent venom release from soft tissue depots that can last for two weeks. This case report illustrates the importance of close hemodynamic and laboratory monitoring after snakebites and describes the administration of continuous antivenom infusion, instead of multidose bolus, to neutralize latent venom release and correct residual coagulopathy. PMID:25664187

Graphical user interface simplifies infusion pump programming and enhances the ability to detect pump-related faults.

PubMed

Syroid, Noah; Liu, David; Albert, Robert; Agutter, James; Egan, Talmage D; Pace, Nathan L; Johnson, Ken B; Dowdle, Michael R; Pulsipher, Daniel; Westenskow, Dwayne R

2012-11-01

Drug administration errors are frequent and are often associated with the misuse of IV infusion pumps. One source of these errors may be the infusion pump's user interface. We used failure modes-and-effects analyses to identify programming errors and to guide the design of a new syringe pump user interface. We designed the new user interface to clearly show the pump's operating state simultaneously in more than 1 monitoring location. We evaluated anesthesia residents in laboratory and simulated environments on programming accuracy and error detection between the new user interface and the user interface of a commercially available infusion pump. With the new user interface, we observed the number of programming errors reduced by 81%, the number of keystrokes per task reduced from 9.2 ± 5.0 to 7.5 ± 5.5 (mean ± SD), the time required per task reduced from 18.1 ± 14.1 seconds to 10.9 ± 9.5 seconds and significantly less perceived workload. Residents detected 38 of 70 (54%) of the events with the new user interface and 37 of 70 (53%) with the existing user interface, despite no experience with the new user interface and extensive experience with the existing interface. The number of programming errors and workload were reduced partly because it took less time and fewer keystrokes to program the pump when using the new user interface. Despite minimal training, residents quickly identified preexisting infusion pump problems with the new user interface. Intuitive and easy-to-program infusion pump interfaces may reduce drug administration errors and infusion pump-related adverse events.

Placebo versus low-dose ketamine infusion in addition to remifentanil target-controlled infusion for conscious sedation during oocyte retrieval: A prospective, double-blinded, randomised controlled trial.

PubMed

Morue, Hélène I; Raj-Lawrence, Shalini; Saxena, Sarah; Delbaere, Anne; Engelman, Edgard; Barvais, Luc A

2018-04-30

Currently, there is no gold standard for monitored anaesthesia care during oocyte retrieval. In our institution, the standard is a conscious sedation technique using a target-controlled infusion (TCI) of remifentanil, titrated to maintain a visual analogue pain score less than 30 mm. This protocol is well accepted by patients but is associated with frequent episodes of respiratory depression. The main objective of this study was to evaluate whether the addition of a continuous intravenous infusion of ketamine could reduce these episodes. Controlled, randomised, prospective, double-blinded study. The current study was conducted in a tertiary-level hospital in Brussels (Belgium) from December 2013 to June 2014. Of the 132 women undergoing oocyte retrieval included, 121 completed the study. After randomisation, patients received either a ketamine infusion (40 μg kg min over 5 min followed by 2.5 μg kg min) or a 0.9% saline infusion in addition to the variable remifentanil TCI. The primary outcome was the number of respiratory depression episodes. Effect site target remifentanil concentrations, side effects, pain score, patient satisfaction and incidence of pregnancy were also recorded. No significant difference in the incidence of respiratory events was noted (pulse oximetry oxygen saturation < 95% was 49% in the ketamine group and 63% in the control group; P = 0.121). No patient required ventilatory support. In the ketamine group, visual analogue pain score and remifentanil concentrations were significantly reduced, but the latter remained above 2 ng ml. Postoperative nausea was less frequent in the ketamine group, 4 versus 15% (P = 0.038). The addition of ketamine did not influence length of stay nor patient satisfaction. The addition of low plasma levels of ketamine to a TCI remifentanil conscious sedation technique did not decrease the incidence nor the severity of respiratory depression. Continuous monitoring of capnography and oxygen saturation is always required. EUDRACT number 2013-003040-23.

Benefit of heparin in peripheral venous and arterial catheters: systematic review and meta-analysis of randomised controlled trials

PubMed Central

Randolph, Adrienne G; Cook, Deborah J; Gonzales, Calle A; Andrew, Maureen

1998-01-01

Objective: To evaluate the effect of heparin on duration of catheter patency and on prevention of complications associated with use of peripheral venous and arterial catheters. Design: Critical appraisal and meta-analysis of 26 randomised controlled trials that evaluated infusion of heparin intermittently or continuously. Thirteen trials of peripheral venous catheters and two of peripheral arterial catheters met criteria for inclusion. Main outcome measures: Data on the populations, interventions, outcomes, and methodological quality. Results: For peripheral venous catheters locked between use flushing with 10 U/ml of heparin instead of normal saline did not reduce the incidence of catheter clotting and phlebitis or improve catheter patency. When heparin was given as a continuous infusion at 1 U/ml the risk of phlebitis decreased (relative risk 0.55; 95% confidence interval 0.39 to 0.77), the duration of patency increased, and infusion failure was reduced (0.88; 0.72 to 1.07). Heparin significantly prolonged duration of patency of radial artery catheters and decreased the risk of clot formation (0.51; 0.42 to 0.61). Conclusions: Use of intermittent heparin flushes at doses of 10 U/ml in peripheral venous catheters locked between use had no benefit over normal saline flush. Infusion of low dose heparin through a peripheral arterial catheter prolonged the duration of patency but further study is needed to establish its benefit for peripheral venous catheters. Key messages Despite almost universal use, agreement has not been reached on the need to administer heparin through peripheral intravascular catheters The results of 13 trials on peripheral venous catheters and two trials on peripheral arterial catheters were critically appraised to clarify what evidence supports the use of heparin Flushing peripheral venous catheters locked between use with heparinised saline at 10 U/ml is no more beneficial than flushing with normal saline Heparin significantly prolongs the duration of peripheral arterial catheter patency and decreases the risk of clot formation In peripheral venous catheters heparin added to the infusion at 1 U/ml decreases phlebitis and may prolong duration of catheter patency and decrease infusion failure PMID:9550955

Treatment with subcutaneous and transdermal fentanyl: results from a population pharmacokinetic study in cancer patients.

PubMed

Oosten, Astrid W; Abrantes, João A; Jönsson, Siv; de Bruijn, Peter; Kuip, Evelien J M; Falcão, Amílcar; van der Rijt, Carin C D; Mathijssen, Ron H J

2016-04-01

Transdermal fentanyl is effective for the treatment of moderate to severe cancer-related pain but is unsuitable for fast titration. In this setting, continuous subcutaneous fentanyl may be used. As data on the pharmacokinetics of continuous subcutaneous fentanyl are lacking, we studied the pharmacokinetics of subcutaneous and transdermal fentanyl. Furthermore, we evaluated rotations from the subcutaneous to the transdermal route. Fifty-two patients treated with subcutaneous and/or transdermal fentanyl for moderate to severe cancer-related pain participated. A population pharmacokinetic model was developed and evaluated using non-linear mixed-effects modelling. For rotations from subcutaneous to transdermal fentanyl, a 1:1 dose conversion ratio was used while the subcutaneous infusion was continued for 12 h (with a 50 % tapering after 6 h). A 6-h scheme with 50 % tapering after 3 h was simulated using the final model. A one-compartment model with first-order elimination and separate first-order absorption processes for each route adequately described the data. The estimated apparent clearance of fentanyl was 49.6 L/h; the absorption rate constant for subcutaneous and transdermal fentanyl was 0.0358 and 0.0135 h(-1), respectively. Moderate to large inter-individual and inter-occasion variability was found. Around rotation from subcutaneous to transdermal fentanyl, measured and simulated plasma fentanyl concentrations rose and increasing side effects were observed. We describe the pharmacokinetics of subcutaneous and transdermal fentanyl in one patient cohort and report several findings that are relevant for clinical practice. Further research is warranted to study the optimal scheme for rotations from the subcutaneous to the transdermal route.

Use of insulin pumps in India: suggested guidelines based on experience and cultural differences.

PubMed

Kesavadev, Jothydev; Das, Ashok Kumar; Unnikrishnan, Ranjit; Joshi, Shashank R; Ramachandran, Ambady; Shamsudeen, Jisha; Krishnan, Gopika; Jothydev, Sunitha; Mohan, Viswanathan

2010-10-01

All type 1 diabetes mellitus (T1DM) subjects and the majority of type 2 diabetes mellitus (T2DM) subjects at one time or another require insulin to sustain life. Syringes and pens are presently the most popular insulin delivery devices. Though in use for more than 3 decades, insulin pumps are now being more commonly used because of their unique ability to continuously infuse insulin, closely mimicking that of physiological secretion from a normal pancreas. Unlike insulin shots with syringes, pump infusion sites need to be changed less frequently. Scientific evidence from published studies have proven added benefit of insulin pumps in improving quality of life, normalizing sugars in recalcitrant diabetes, improving sexual function, and relieving the intractable pain of neuropathy. In the western world, pumps are commonly used with T1DM subjects, whereas in India 80% of pumpers are T2DM subjects. The success of insulin pump therapy depends on selection of the right candidate, extensive education, motivation, and implementing the sophisticated programs with skill. However, all affordable patients are not ideal candidates for pump therapy because for successful continuation of pump therapy other inclusion criteria should also be fulfilled. Among the other indications discussed are a high level of insulin resistance, brittle diabetes, chronic kidney disease on renal replacement therapy, and continuous glucose monitoring pattern strongly suggesting need for a variable basal insulin infusion rate. In International Diabetes Foundation data released in 2009, estimated diabetes prevalence for 2010 is 285 million, representing 6.4% of the world's adult population, with a prediction that by 2030 the number of people with diabetes will have increased to 438 million. Considering this massive growth in T2DM and its propensity after 10–15 years to lead to an insulin-deficient state, available evidence from studies is a compelling indication not to deny the benefits of continuous subcutaneous insulin infusion in selected T2DM subjects. This article aims at suggesting guidelines based on clinical experience and cultural diversity for India and developing countries.

Use of Insulin Pumps in India: Suggested Guidelines Based on Experience and Cultural Differences

PubMed Central

Das, Ashok Kumar; Unnikrishnan, Ranjit; Joshi, Shashank R.; Ramachandran, Ambady; Shamsudeen, Jisha; Krishnan, Gopika; Jothydev, Sunitha; Mohan, Viswanathan

2010-01-01

Abstract All type 1 diabetes mellitus (T1DM) subjects and the majority of type 2 diabetes mellitus (T2DM) subjects at one time or another require insulin to sustain life. Syringes and pens are presently the most popular insulin delivery devices. Though in use for more than 3 decades, insulin pumps are now being more commonly used because of their unique ability to continuously infuse insulin, closely mimicking that of physiological secretion from a normal pancreas. Unlike insulin shots with syringes, pump infusion sites need to be changed less frequently. Scientific evidence from published studies have proven added benefit of insulin pumps in improving quality of life, normalizing sugars in recalcitrant diabetes, improving sexual function, and relieving the intractable pain of neuropathy. In the western world, pumps are commonly used with T1DM subjects, whereas in India 80% of pumpers are T2DM subjects. The success of insulin pump therapy depends on selection of the right candidate, extensive education, motivation, and implementing the sophisticated programs with skill. However, all affordable patients are not ideal candidates for pump therapy because for successful continuation of pump therapy other inclusion criteria should also be fulfilled. Among the other indications discussed are a high level of insulin resistance, brittle diabetes, chronic kidney disease on renal replacement therapy, and continuous glucose monitoring pattern strongly suggesting need for a variable basal insulin infusion rate. In International Diabetes Foundation data released in 2009, estimated diabetes prevalence for 2010 is 285 million, representing 6.4% of the world's adult population, with a prediction that by 2030 the number of people with diabetes will have increased to 438 million. Considering this massive growth in T2DM and its propensity after 10–15 years to lead to an insulin-deficient state, available evidence from studies is a compelling indication not to deny the benefits of continuous subcutaneous insulin infusion in selected T2DM subjects. This article aims at suggesting guidelines based on clinical experience and cultural diversity for India and developing countries. PMID:20807118

[Usefullness of transesophageal echocardiography in early detection of coronary spasm].

PubMed

Sagara, M; Haraguchi, M; Hamu, Y; Isowaki, S; Yoshimura, N

1996-04-01

Intraoperative transesophageal echocardiography (TEE) was performed on a 62-year-old man who underwent abdominal aortic replacement for abdominal aortic aneurysm under general anesthesia combined with epidural anesthesia. Coronary artery spasm occurred after unexpected massive hemorrhage, and TEE showed hypokinesis in the posterior-inferior left ventricular wall. The changes in TEE preceded the ST elevation in the ECG. Bolus infusion of isosorbide dinitrate and continuous infusion of nitroglycerin alleviated these changes. TEE enabled us to detect and evaluate coronary spasm before the appearance of ST changes in ECG.

The Future of Intensive Care Unit Sedation: A Report of Continuous Infusion Ketamine as an Alternative Sedative Agent.

PubMed

Benken, Scott T; Goncharenko, Alexandra

2017-10-01

This report describes a patient case utilizing a nontraditional sedative, continuous infusion ketamine, as an alternative agent for intensive care unit (ICU) sedation. A 27-year-old female presented for neurosurgical management of a coup contrecoup injury, left temporal fracture, epidural hemorrhage (EDH), and temporal contusion leading to sustained mechanical ventilation. The patient experienced profound agitation during mechanical ventilation and developed adverse effects with all traditional sedatives: benzodiazepines, dexmedetomidine, opioids, and propofol. Ketamine was titrated to effect and eliminated the need for other agents. This led to successful ventilator weaning, extubation, and transition of care. Given the unique side effect profile of ketamine, it is imperative that information is disseminated on potential utilization of this agent. More information is needed regarding dosing, monitoring, and long-term effects of utilizing ketamine as a continuous ICU sedative, but given the analgesia, anesthesia, and cardiopulmonary stability, future utilization of this medication for this indication seems promising.

Design and characterization of hydrogel-based microfluidic devices with biomimetic solute transport networks

PubMed Central

Koo, Hyung-Jun

2017-01-01

Hydrogel could serve as a matrix material of new classes of solar cells and photoreactors with embedded microfluidic networks. These devices mimic the structure and function of plant leaves, which are a natural soft matter based microfluidic system. These unusual microfluidic-hydrogel devices with fluid-penetrable medium operate on the basis of convective-diffusive mechanism, where the liquid is transported between the non-connected channels via molecular permeation through the hydrogel. We define three key designs of such hydrogel devices, having linear, T-shaped, and branched channels and report results of numerical simulation of the process of their infusion with solute carried by the incoming fluid. The computational procedure takes into account both pressure-driven convection and concentration gradient-driven diffusion in the permeable gel matrix. We define the criteria for evaluation of the fluid infusion rate, uniformity, solute loss by outflow and overall performance. The T-shaped channel network was identified as the most efficient one and was improved further by investigating the effect of the channel-end secondary branches. Our parallel experimental data on the pattern of solute infusions are in excellent agreement with the simulation. These network designs can be applied to a broad range of novel microfluidic materials and soft matter devices with distributed microchannel networks. PMID:28396708

Continuous subcutaneous use of levetiracetam: a retrospective review of tolerability and clinical effects.

PubMed

Rémi, Constanze; Lorenzl, Stefan; Vyhnalek, Birgit; Rastorfer, Karin; Feddersen, Berend

2014-12-01

To evaluate the tolerability and clinical effects of subcutaneous (SC) levetiracetam for the treatment of epileptic seizures in a palliative care setting, we conducted a retrospective chart review of patients treated with subcutaneous levetiracetam in the Department of Palliative Medicine at the University Munich, between September 2006 and March 2013. The following parameters were extracted from the charts: reason for antiepileptic drug treatment, daily dose, concentration, infusion rate, co-administration of other drugs, and clinical effects. Furthermore, the charts were screened for signs of adverse drug reactions, e.g., irritation or pain at the infusion site. We identified 20 patients that were treated with levetiracetam SC in the inpatient (n = 7) and outpatient (n = 13) settings. Most patients (n = 17) tolerated the subcutaneous infusion well. Nineteen patients (95%) received levetiracetam in combination with other drugs. These were mainly metamizol (80%), midazolam (75%), and morphine (45%). The median dose of levetiracetam was 95.8 mg/h (SD 37 mg/h), median osmolarity of the infusion solution 2203 mOsmol/L (SD 717 mOsmol/L), and infusion rate 2 mL/h (SD 2.4 ml/h). In 16 patients (80%), seizures were controlled and status epilepticus were interrupted, respectively. We conclude that SC levetiracetam is an effective treatment and well tolerated in the palliative care setting.

Extended infusion of beta-lactam antibiotics: optimizing therapy in critically-ill patients in the era of antimicrobial resistance.

PubMed

Rizk, Nesrine A; Kanafani, Zeina A; Tabaja, Hussam Z; Kanj, Souha S

2017-07-01

Beta-lactams are at the cornerstone of therapy in critical care settings, but their clinical efficacy is challenged by the rise in bacterial resistance. Infections with multi-drug resistant organisms are frequent in intensive care units, posing significant therapeutic challenges. The problem is compounded by a dearth in the development of new antibiotics. In addition, critically-ill patients have unique physiologic characteristics that alter the drugs pharmacokinetics and pharmacodynamics. Areas covered: The prolonged infusion of antibiotics (extended infusion [EI] and continuous infusion [CI]) has been the focus of research in the last decade. As beta-lactams have time-dependent killing characteristics that are altered in critically-ill patients, prolonged infusion is an attractive approach to maximize their drug delivery and efficacy. Several studies have compared traditional dosing to EI/CI of beta-lactams with regard to clinical efficacy. Clinical data are primarily composed of retrospective studies and some randomized controlled trials. Several reports show promising results. Expert commentary: Reviewing the currently available evidence, we conclude that EI/CI is probably beneficial in the treatment of critically-ill patients in whom an organism has been identified, particularly those with respiratory infections. Further studies are needed to evaluate the efficacy of EI/CI in the management of infections with resistant organisms.

Control Law Design for Propofol Infusion to Regulate Depth of Hypnosis: A Nonlinear Control Strategy

PubMed Central

Khaqan, Ali; Bilal, Muhammad; Ilyas, Muhammad; Ijaz, Bilal; Ali Riaz, Raja

2016-01-01

Maintaining the depth of hypnosis (DOH) during surgery is one of the major objectives of anesthesia infusion system. Continuous administration of Propofol infusion during surgical procedures is essential but increases the undue load of an anesthetist in operating room working in a multitasking setup. Manual and target controlled infusion (TCI) systems are not good at handling instabilities like blood pressure changes and heart rate variability arising due to interpatient variability. Patient safety, large interindividual variability, and less postoperative effects are the main factors to motivate automation in anesthesia. The idea of automated system for Propofol infusion excites the control engineers to come up with a more sophisticated and safe system that handles optimum delivery of drug during surgery and avoids postoperative effects. In contrast to most of the investigations with linear control strategies, the originality of this research work lies in employing a nonlinear control technique, backstepping, to track the desired hypnosis level of patients during surgery. This effort is envisioned to unleash the true capabilities of this nonlinear control technique for anesthesia systems used today in biomedical field. The working of the designed controller is studied on the real dataset of five patients undergoing surgery. The controller tracks the desired hypnosis level within the acceptable range for surgery. PMID:27293475

[High dose L-dopa infusion during general anesthesia for gastrectomy in a patient with parkinsonism].

PubMed

Horai, Tetsuya; Nishiyama, Tomoki; Yamamoto, Hirotoshi; Hanaoka, Kazuo

2002-01-01

A 68-year-old man with parkinsonism was scheduled for gastrectomy. Levodopa 1400 mg, droxidopa 300 mg and bromocriptine-mesylate 7.5 mg had been administered orally per day to control the symptom before surgery. On the day before surgery, oral medication was stopped and intravenous infusion of levodopa 100 mg.h-1 was started. Without any premedication but with levodopa infusion, anesthesia was induced with thiopental 175 mg and fentanyl 0.05 mg. Tracheal intubation was facilitated with vecuronium 6 mg and an epidural catheter was inserted. Anesthesia was maintained with O2, N2O and sevoflurane, combined with epidural block using mepivacaine. When blood pressure decreased, phenylephrine but not ephedrine was effective to increase blood pressure. Intravenous infusion of levodopa was continued for 19 days with decreasing doses from 8th postoperative day when injection of levodopa into the intestinal tube was started. On the 53rd day, he left the hospital without any complications. Serum concentrations of levodopa during and after surgery were 50 to 100 times higher than the therapeutic levels. However, he developed no complications, which suggests a wide safety range of levodopa. In conclusion, high dose levodopa infusion was effective in controlling the symptoms of Parkinsonism during general anesthesia.

Control Law Design for Propofol Infusion to Regulate Depth of Hypnosis: A Nonlinear Control Strategy.

PubMed

Khaqan, Ali; Bilal, Muhammad; Ilyas, Muhammad; Ijaz, Bilal; Ali Riaz, Raja

2015-01-01

Maintaining the depth of hypnosis (DOH) during surgery is one of the major objectives of anesthesia infusion system. Continuous administration of Propofol infusion during surgical procedures is essential but increases the undue load of an anesthetist in operating room working in a multitasking setup. Manual and target controlled infusion (TCI) systems are not good at handling instabilities like blood pressure changes and heart rate variability arising due to interpatient variability. Patient safety, large interindividual variability, and less postoperative effects are the main factors to motivate automation in anesthesia. The idea of automated system for Propofol infusion excites the control engineers to come up with a more sophisticated and safe system that handles optimum delivery of drug during surgery and avoids postoperative effects. In contrast to most of the investigations with linear control strategies, the originality of this research work lies in employing a nonlinear control technique, backstepping, to track the desired hypnosis level of patients during surgery. This effort is envisioned to unleash the true capabilities of this nonlinear control technique for anesthesia systems used today in biomedical field. The working of the designed controller is studied on the real dataset of five patients undergoing surgery. The controller tracks the desired hypnosis level within the acceptable range for surgery.

Stimulation of body weight increase and epiphyseal cartilage growth by insulin like growth factor

NASA Technical Reports Server (NTRS)

Ellis, S.

1981-01-01

The ability of insulin-like growth factor (IGF) to induce growth in hypophysectomized immature rats was tested by continuous infusion of the partially purified factor at daily doses of 6, 21, and 46 mU for an 8-day period. A dose-dependent growth of the proximal epiphyseal cartilage of the tibia and an associated stimulation of the primary spongiosa were produced by these amounts of IGF. The two highest doses of IGF also resulted in dose-dependent increases of body weight. Gel permeation of the sera at neutrality showed that the large-molecular-weight IGF binding protein was not induced by the infusion of IGF, whereas it ws generated in the sera of hypophysectomized rats that were infused with daily doses of 86 mU of human growth hormone.

Adjunct Ketamine Use in the Management of Severe Ethanol Withdrawal.

PubMed

Pizon, Anthony F; Lynch, Michael J; Benedict, Neal J; Yanta, Joseph H; Frisch, Adam; Menke, Nathan B; Swartzentruber, Greg S; King, Andrew M; Abesamis, Michael G; Kane-Gill, Sandra L

2018-05-08

Ketamine offers a plausible mechanism with favorable kinetics in treatment of severe ethanol withdrawal. The purpose of this study is to determine if a treatment guideline using an adjunctive ketamine infusion improves outcomes in patients suffering from severe ethanol withdrawal. Retrospective observational cohort study. Academic tertiary care hospital. Patients admitted to the ICU and diagnosed with delirium tremens by Diagnostic and Statistical Manual of Mental Disorders V criteria. Pre and post guideline, all patients were treated in a symptom-triggered fashion with benzodiazepines and/or phenobarbital. Postguideline, standard symptom-triggered dosing continued as preguideline, plus, the patient was initiated on an IV ketamine infusion at 0.15-0.3 mg/kg/hr continuously until delirium resolved. Based upon withdrawal severity and degree of agitation, a ketamine bolus (0.3 mg/kg) was provided prior to continuous infusion in some patients. A total of 63 patients were included (29 preguideline; 34 postguideline). Patients treated with ketamine were less likely to be intubated (odds ratio, 0.14; p < 0.01; 95% CI, 0.04-0.49) and had a decreased ICU stay by 2.83 days (95% CI, -5.58 to -0.089; p = 0.043). For ICU days outcome, correlation coefficients were significant for alcohol level and total benzodiazepine dosing. For hospital days outcome, correlation coefficients were significant for patient age, aspartate aminotransferase, and alanine aminotransferase level. Regression revealed the use of ketamine was associated with a nonsignificant decrease in hospital stay by 3.66 days (95% CI, -8.40 to 1.08; p = 0.13). Mechanistically, adjunctive therapy with ketamine may attenuate the demonstrated neuroexcitatory contribution of N-methyl-D-aspartate receptor stimulation in severe ethanol withdrawal, reduce the need for excessive gamma-aminobutyric acid agonist mediated-sedation, and limit associated morbidity. A ketamine infusion in patients with delirium tremens was associated with reduced gamma-aminobutyric acid agonist requirements, shorter ICU length of stay, lower likelihood of intubation, and a trend toward a shorter hospitalization.

Determination of minimal steady-state plasma level of diazepam causing seizure threshold elevation in rats.

PubMed

Dhir, Ashish; Rogawski, Michael A

2018-05-01

Diazepam, administered by the intravenous, oral, or rectal routes, is widely used for the management of acute seizures. Dosage forms for delivery of diazepam by other routes of administration, including intranasal, intramuscular, and transbuccal, are under investigation. In predicting what dosages are necessary to terminate seizures, the minimal exposure required to confer seizure protection must be known. Here we administered diazepam by continuous intravenous infusion to obtain near-steady-state levels, which allowed an assessment of the minimal levels that elevate seizure threshold. The thresholds for various behavioral seizure signs (myoclonic jerk, clonus, and tonus) were determined with the timed intravenous pentylenetetrazol seizure threshold test in rats. Diazepam was administered to freely moving animals by continuous intravenous infusion via an indwelling jugular vein cannula. Blood samples for assay of plasma levels of diazepam and metabolites were recovered via an indwelling cannula in the contralateral jugular vein. The pharmacokinetic parameters of diazepam following a single 80-μg/kg intravenous bolus injection were determined using a noncompartmental pharmacokinetic approach. The derived parameters V d , CL, t 1/2α (distribution half-life) and t 1/2β (terminal half-life) for diazepam were, respectively, 608 mL, 22.1 mL/min, 13.7 minutes, and 76.8 minutes, respectively. Various doses of diazepam were continuously infused without or with an initial loading dose. At the end of the infusions, the thresholds for various behavioral seizure signs were determined. The minimal plasma diazepam concentration associated with threshold elevations was estimated at approximately 70 ng/mL. The active metabolites nordiazepam, oxazepam, and temazepam achieved levels that are expected to make only minor contributions to the threshold elevations. Diazepam elevates seizure threshold at steady-state plasma concentrations lower than previously recognized. The minimally effective plasma concentration provides a reference that may be considered when estimating the diazepam exposure required for acute seizure treatment. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

Overnight closed-loop insulin delivery with model predictive control: assessment of hypoglycemia and hyperglycemia risk using simulation studies.

PubMed

Wilinska, Malgorzata E; Budiman, Erwin S; Taub, Marc B; Elleri, Daniela; Allen, Janet M; Acerini, Carlo L; Dunger, David B; Hovorka, Roman

2009-09-01

Hypoglycemia and hyperglycemia during closed-loop insulin delivery based on subcutaneous (SC) glucose sensing may arise due to (1) overdosing and underdosing of insulin by control algorithm and (2) difference between plasma glucose (PG) and sensor glucose, which may be transient (kinetics origin and sensor artifacts) or persistent (calibration error [CE]). Using in silico testing, we assessed hypoglycemia and hyperglycemia incidence during over-night closed loop. Additionally, a comparison was made against incidence observed experimentally during open-loop single-night in-clinic studies in young people with type 1 diabetes mellitus (T1DM) treated by continuous SC insulin infusion. Simulation environment comprising 18 virtual subjects with T1DM was used to simulate overnight closed-loop study with a model predictive control (MPC) algorithm. A 15 h experiment started at 17:00 and ended at 08:00 the next day. Closed loop commenced at 21:00 and continued for 11 h. At 18:00, protocol included meal (50 g carbohydrates) accompanied by prandial insulin. The MPC algorithm advised on insulin infusion every 15 min. Sensor glucose was obtained by combining model-calculated noise-free interstitial glucose with experimentally derived transient and persistent sensor artifacts associated with FreeStyle Navigator (FSN). Transient artifacts were obtained from FSN sensor pairs worn by 58 subjects with T1DM over 194 nighttime periods. Persistent difference due to FSN CE was quantified from 585 FSN sensor insertions, yielding 1421 calibration sessions from 248 subjects with diabetes. Episodes of severe (PG < or = 36 mg/dl) and significant (PG < or = 45 mg/dl) hypoglycemia and significant hyperglycemia (PG > or = 300 mg/dl) were extracted from 18,000 simulated closed-loop nights. Severe hypoglycemia was not observed when FSN CE was less than 45%. Hypoglycemia and hyperglycemia incidence during open loop was assessed from 21 overnight studies in 17 young subjects with T1DM (8 males; 13.5 +/- 3.6 years of age; body mass index 21.0 +/- 4.0 kg/m2; duration diabetes 6.4 +/- 4.1 years; hemoglobin A1c 8.5% +/- 1.8%; mean +/- standard deviation) participating in the Artificial Pancreas Project at Cambridge. Severe and significant hypoglycemia during simulated closed loop occurred 0.75 and 17.11 times per 100 person years compared to 1739 and 3479 times per 100 person years during experimental open loop, respectively. Significant hyperglycemia during closed loop and open loop occurred 75 and 15,654 times per 100 person years, respectively. The incidence of severe and significant hypoglycemia reduced 2300- and 200-fold, respectively, during stimulated overnight closed loop with MPC compared to that observed during open-loop overnight clinical studies in young subjects with T1DM. Hyperglycemia was 200 times less likely. Overnight closed loop with the FSN and the MPC algorithm is expected to reduce substantially the risk of hypoglycemia and hyperglycemia. 2009 Diabetes Technology Society.

Maintenance of plasma branched-chain amino acid concentrations during glucose infusion directs essential amino acids to extra-mammary tissues in lactating dairy cows.

PubMed

Curtis, Richelle V; Kim, Julie J M; Doelman, John; Cant, John P

2018-05-01

The objectives of this study were to investigate the effects of branched-chain AA (BCAA) supplementation when glucose is infused postruminally into lactating dairy cows consuming a diet low in crude protein (CP) and to test the hypothesis that low BCAA concentrations are responsible for the poor stimulation of milk protein yield by glucose. Twelve early-lactation Holstein cows were randomly assigned to 15% and 12% CP diets in a switchback design of 6-wk periods. Cows consuming the 12% CP diet received 96-h continuous jugular infusions of saline and 1 kg/d of glucose with 0, 75, or 150 g/d of BCAA in a Latin square sequence of treatments. Compared with saline, glucose infusion did not affect dry matter intake but increased milk yield by 2.2 kg/d and milk protein and lactose yields by 63 and 151 g/d, respectively. Mammary plasma flow increased 36% during glucose infusion compared with saline infusion, possibly because of a 31% decrease in total acetate plus β-hydroxybutyrate concentrations. Circulating concentrations of total essential AA and BCAA decreased 19 and 31%, respectively, during infusion of glucose, yet net mammary uptakes of AA remained unchanged compared with saline infusion. The addition of 75 and 150 g/d of BCAA to glucose infusions increased arterial concentrations of BCAA to 106 and 149%, respectively, of the concentrations in saline-infused cows, but caused a decrease in concentrations of non-branched-chain essential AA in plasma, as well as their mammary uptakes and milk protein yields. Plasma urea concentration was not affected by BCAA infusion, indicating no change in catabolism of AA. The lack of mammary and catabolic effects leads us to suggest that BCAA exerted their effects on plasma concentrations of the other essential AA by stimulating utilization in skeletal muscle for protein accretion. Results indicate that the glucose effect on milk protein yield was not limited by low BCAA concentrations, and that a stimulation of extra-mammary use of non-branched-chain essential amino acids by BCAA led to a decrease in milk protein yield. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

[Continuous low volume infusion of hydroxyethyl starch as an option of water balance correction in patients with gestosis].

PubMed

Zhurova, A A; Ekstrem, A V; Popov, A S

2010-01-01

The method of long-term continuous low-volume infusion of hydroxyethyl starch (low-flow low volume correction HES) is administrated for correction of fluid balance disorders. The method is aimed to improve the outcomes in preeclamsia patients with multiple organ dysfunction and failure, as the most severe manifestation of system inflammatory response syndrome. After 4 days of the intensive care with application of the developed method in patients with preeclamsia the total body water level is decreased to the normal physiological level, the oedemas are significantly reduced or ceased, the haemodynamics stabilizes, which leads to the reduce of neurologic symptoms. The suggested method of low-flow low volume correction HES, in dose of 15 ml/kg/day is a significant addition to the existing methods of homeostasis and preeclampsia correction.

Continuous subcutaneous infusion of opiates at end-of-life.

PubMed

Anderson, Stacey L; Shreve, Scott T

2004-06-01

To review pertinent controlled trials using the continuous subcutaneous infusion of opioids (CSIO) at end-of-life and offer insight to pharmacists and clinicians into the appropriate use of this route of administration. A MEDLINE search for information regarding the subcutaneous administration of opioids in terminally ill patients (1975-December 2002) was conducted using the key words subcutaneous, narcotics, morphine, hydromorphone, fentanyl, pain, hospices, and palliative care. Additional references were located through review of bibliographies of the articles cited. Case reports and postsurgical studies were excluded. Searches were limited to English-language studies using humans. Experimental and observational studies were evaluated, using prospective trials as the evidence base for conclusions and including pertinent retrospective trials as they relate to the subcutaneous infusion of opioids at end-of-life. CSIO is effective and safe for use in terminal illness. Appropriate situations for consideration of CSIO are when difficulties arise in using the oral route, standard oral opiate therapy has failed adequate trials, the patient has limited intravenous access, adequate supervision of the CSIO is present, and CSIO will not unduly limit the functional activity of the patient. CSIO has a proven role in the management of pain at end-of-life. CSIO should not be considered the first route for administration of opiates, but does offer distinct advantages in the appropriate setting. CSIO continues to be a choice for end-of-life patients and is gradually becoming a standard practice in palliative medicine.

Exercise limits the production of endothelin in the coronary vasculature

PubMed Central

de Beer, Vincent J.; Bender, Shawn B.; Taverne, Yannick J.; Gao, Fen; Duncker, Dirk J.; Laughlin, M. Harold

2011-01-01

We previously demonstrated that endothelin (ET)-mediated coronary vasoconstriction wanes with increasing exercise intensity via a nitric oxide- and prostacyclin-dependent mechanism (Ref. 23). Therefore, we hypothesized that the waning of ET coronary vasoconstriction during exercise is the result of decreased production of ET and/or decreased ET receptor sensitivity. We investigated coronary ET receptor sensitivity using intravenous infusion of ET and coronary ET production using intravenous infusion of the ET precursor Big ET, at rest and during continuous treadmill exercise at 3 km/h in 16 chronically instrumented swine. In the systemic vasculature, Big ET and ET induced similar changes in hemodynamic parameters at rest and during continuous exercise at 3 km/h, indicating that exercise does not alter ET production or receptor sensitivity in the systemic vasculature. In the coronary vasculature, infusion of ET resulted in similar dose-dependent decreases in coronary blood flow and coronary venous oxygen tension and saturation at rest and during exercise. In contrast, administration of Big ET resulted in dose-dependent decreases in coronary blood flow, as well as coronary venous oxygen tension and saturation at rest. These effects of Big ET were significantly reduced during exercise. Altogether, our data indicate that continuous exercise at 3 km/h attenuates ET-mediated coronary vasoconstriction through reduced production of ET from Big ET rather than through reduced ET sensitivity of the coronary vasculature. The decreased ET production during exercise likely contributes to metabolic coronary vasodilation. PMID:21317308

Efficacy and Safety of Continuous Micro-Pump Infusion of 3% Hypertonic Saline combined with Furosemide to Control Elevated Intracranial Pressure.

PubMed

Li, Yuqian; Li, Zhihong; Li, Min; Yang, Yanlong; Wang, Bao; Gao, Li; Zhang, Xingye; Cheng, Hongyu; Fang, Wei; Zhao, Bo; Wang, Boliang; Gao, Guodong; Li, Lihong

2015-06-17

Elevated intracranial pressure is one of the most common problems in patients with diverse intracranial disorders, leading to increased morbidity and mortality. Effective management for increased intracranial pressure is based mainly on surgical and medical techniques with hyperosmolar therapy as one of the core medical treatments. The study aimed to explore the effects of continuous micro-pump infusions of 3% hypertonic saline combined with furosemide on intracranial pressure control. We analyzed data on 56 eligible participants with intracranial pressure >20 mmHg from March 2013 to July 2014. The target was to increase and maintain plasma sodium to a level between 145 and 155 mmol/L and osmolarity to a level of 310 to 320 mOsmol/kg. Plasma sodium levels significantly increased from 138±5 mmol/L at admission to 151±3 mmol/L at 24 h (P<0.01). Osmolarity increased from 282±11 mOsmol/kg at baseline to 311±8 mOsmol/kg at 24 h (P<0.01). Intracranial pressure significantly decreased from 32±7 mmHg to 15±6 mmHg at 24 h (P<0.01). There was a significant improvement in CPP (P<0.01). Moreover, central venous pressure, mean arterial pressure, and Glasgow Coma Scale slightly increased. However, these changes were not statistically significant. Continuous infusion of 3% hypertonic saline + furosemide is effective and safe for intracranial pressure control.

In-hospital pediatric cardiac arrest in Spain.

PubMed

López-Herce, Jesús; del Castillo, Jimena; Cañadas, Sonia; Rodríguez-Núñez, Antonio; Carrillo, Angel

2014-03-01

The objective was to analyze the characteristics and prognostic factors of in-hospital pediatric cardiac arrest in Spain. A prospective observational study was performed to examine in-hospital pediatric cardiac arrest. Two hundred children were studied, aged between 1 month and 18 years, with in-hospital cardiac arrest. Univariate and multivariate logistic regression analyses were performed to assess the influence of each factor on survival to hospital discharge. Return of spontaneous circulation was achieved in 74% of the patients and 41% survived to hospital discharge. The survival rate was significantly higher than that reported in a previous Spanish study 10 years earlier (25.9%). In the univariate analysis, the factors related to mortality were body weight higher than 10 kg; continuous infusion of vasoactive drugs prior to cardiac arrest; sepsis and neurological disorders as causes of cardiac arrest, the need for treatment with adrenaline, bicarbonate, and volume expansion, and prolonged cardiopulmonary resuscitation. In the multivariate analysis, the factors related to mortality were hematologic/oncologic diseases, continuous infusion of vasoactive drugs prior to cardiac arrest, cardiopulmonary resuscitation for more than 20 min, and treatment with bicarbonate and volume expansion. Survival after in-hospital cardiac arrest in children has significantly improved in recent years. The factors related to in-hospital mortality were hematologic/oncologic diseases, continuous infusion of vasoactive drugs prior to cardiac arrest, the duration of cardiopulmonary resuscitation, and treatment with bicarbonate and volume expansion. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

GH Mediates Exercise-Dependent Activation of SVZ Neural Precursor Cells in Aged Mice

PubMed Central

Blackmore, Daniel G.; Vukovic, Jana; Waters, Michael J.; Bartlett, Perry F.

2012-01-01

Here we demonstrate, both in vivo and in vitro, that growth hormone (GH) mediates precursor cell activation in the subventricular zone (SVZ) of the aged (12-month-old) brain following exercise, and that GH signaling stimulates precursor activation to a similar extent to exercise. Our results reveal that both addition of GH in culture and direct intracerebroventricular infusion of GH stimulate neural precursor cells in the aged brain. In contrast, no increase in neurosphere numbers was observed in GH receptor null animals following exercise. Continuous infusion of a GH antagonist into the lateral ventricle of wild-type animals completely abolished the exercise-induced increase in neural precursor cell number. Given that the aged brain does not recover well after injury, we investigated the direct effect of exercise and GH on neural precursor cell activation following irradiation. This revealed that physical exercise as well as infusion of GH promoted repopulation of neural precursor cells in irradiated aged animals. Conversely, infusion of a GH antagonist during exercise prevented recovery of precursor cells in the SVZ following irradiation. PMID:23209615

Complication Rates of 3% Hypertonic Saline Infusion Through Peripheral Intravenous Access.

PubMed

Perez, Claudia Andira; Figueroa, Stephen A

2017-06-01

Hyperosmolar therapy with hypertonic saline (HTS) is a cornerstone in the management of intracranial hypertension and hyponatremia in the neurological intensive care unit. Theoretical safety concerns remain for infiltration, thrombophlebitis, tissue ischemia, and venous thrombosis associated with continuous 3% HTS administered via peripheral intravenous (pIV) catheters. It is common practice at many institutions to allow only central venous catheter infusion of 3% HTS. Hospital policy was changed to allow the administration of 3% HTS via 16- to 20-gauge pIVs to a maximum infusion rate of 50 mL/h in patients without central venous access. We prospectively monitored patients who received peripheral 3% HTS as part of a quality improvement project. We documented gauge, location, maximum infusion rate, and total hours of administration. Patients were assessed for infiltration, erythema, swelling, phlebitis, thrombosis, and line infection. There were 28 subjects across 34 peripheral lines monitored. Overall, subjects received 3% HTS for a duration between 1 and 124 hours with infusion rates of 30 to 50 mL/h. The rate of complications observed was 10.7% among all subjects. Documented complications included infiltration (n = 2), with an incidence of 6%, and thrombophlebitis (n = 1), with an incidence of 3%. There has been a long concern among healthcare providers, including nursing staff, in regard to pIV administration of prolonged 3% HTS infusion therapy. Our study indicates that peripheral administration of 3% HTS carries a low risk of minor, nonlimb, or life-threatening complications. Although central venous infusion may reduce the risk of these minor complications, it may increase the risk of more serious complications such as large vessel thrombosis, bloodstream infection, pneumothorax, and arterial injury. The concern regarding the risks of pIV administration of 3% HTS may be overstated and unfounded.

Analysis of the Environmental Impact of Insulin Infusion Sets Based on Loss of Resources with Waste

PubMed Central

Pfützner, Andreas; Musholt, Petra B; Malmgren-Hansen, Bjoern; Nilsson, Nils H; Forst, Thomas

2011-01-01

Insulin pump therapy [continuous subcutaneous insulin infusion (CSII)] requires regular change of infusion sets every 2-3 days in order to minimize the risk of skin irritations or other adverse events. This has been discussed to be a potential burden to the environment. The purpose of this analysis was to perform an environmental assessment of insulin pump infusion sets based on loss of resources occurring during incineration of the discarded products and by means of a lifecycle concept used to weight a material in relation to its rareness on earth and its consumption. In addition to five infusion sets (Inset30, InsetII, Comfort, Quick-set, and Cleo), a patch pump (Omnipod) was also included in this analysis. The annual loss in waste of the so called “person reserve” of 3 days of catheter use was compared with daily consumption of a cup of coffee in a disposable paper cup and to a soft drink in an aluminum can. The weight-based loss in resources through waste for the infusion sets (except for Cleo) corresponded to 70-200% of the loss of resources for a coffee cup (Cleo, 320%; Omnipod, 1,821,600%) and to 1-3% of the loss from an aluminum soft drink can (Cleo, 5%; Omnipod, 31,200%). The loss or resources by use of infusion sets used in insulin pump therapy appears to be low and is similar to the burden induced by the uptake of one cup of coffee per day. The loss or resources with regular CSII is considerably lower than the loss or resources induced by patch pumps. PMID:21880223

Periodic Extraction of Interstitial Fluid from the Site of Subcutaneous Insulin Infusion for the Measurement of Glucose: A Novel Single-Port Technique for the Treatment of Type 1 Diabetes Patients

PubMed Central

Lindpointner, Stefan; Korsatko, Stefan; Tutkur, Dina; Bodenlenz, Manfred; Pieber, Thomas R.

2013-01-01

Abstract Background Treatment of type 1 diabetes patients could be simplified if the site of subcutaneous insulin infusion could also be used for the measurement of glucose. This study aimed to assess the agreement between blood glucose concentrations and glucose levels in the interstitial fluid (ISF) that is extracted from the insulin infusion site during periodic short-term interruptions of continuous subcutaneous insulin infusion (CSII). Subjects and Methods A perforated cannula (24 gauge) was inserted into subcutaneous adipose tissue of C-peptide-negative type 1 diabetes subjects (n=13) and used alternately to infuse rapid-acting insulin (100 U/mL) and to extract ISF glucose during a fasting period and after ingestion of a standard oral glucose load (75 g). Results Although periodically interrupted for extracting glucose (every hour for approximately 10 min), insulin infusion with the cannula was adequate to achieve euglycemia during fasting and to restore euglycemia after glucose ingestion. Furthermore, the ISF-derived estimates of plasma glucose levels agreed well with plasma glucose concentrations. Correlation coefficient and median absolute relative difference values were found to be 0.95 and 8.0%, respectively. Error grid analysis showed 99.0% of all ISF glucose values within clinically acceptable Zones A and B (83.5% Zone A, 15.5% Zone B). Conclusions Results show that ISF glucose concentrations measured at the insulin infusion site during periodic short-term interruptions of CSII closely reflect blood glucose levels, thus suggesting that glucose monitoring and insulin delivery may be performed alternately at the same tissue site. A single-port device of this type could be used to simplify and improve glucose management in diabetes. PMID:23126579

Intra-VTA infusions of the substance P analogue, DiMe-C7, and intra-accumbens infusions of amphetamine induce analgesia in the formalin test for tonic pain.

PubMed

Altier, N; Stewart, J

1993-11-19

Experiments were designed to examine the analgesic effects of SP injected into the ventral tegmental area (VTA). Rats received bilateral intra-VTA infusions of 3.0 micrograms/0.5 microliter/side of the SP analogue, DiMe-C7, or the vehicle, either immediately prior to or 25 min following an injection of 0.05 ml of 2.5% formalin into one hind paw. Formalin-induced pain responses were continuously recorded for 75 min. DiMe-C7 attenuated pain responses for approximately 30 min; the analgesia was more potent and longer-lasting when DiMe-C7 was infused after, rather than prior to, the early pain phase. In another set of experiments, rats were tested in the formalin test immediately following bilateral infusions of amphetamine (1.5 or 2.5 micrograms/0.05 microliter/side) into either the medial prefrontal cortex (mPFC) or the nucleus accumbens septi (NAS). Amphetamine failed to alter pain responses when infused into the mPFC, but both doses attenuated pain responses during 25 min when infused into the NAS. There was no evidence for pain inhibition in the tail-flick test for phasic pain following either intra-VTA DiMe-C7 or intra-NAS amphetamine. The finding that intra-VTA DiMe-C7 and intra-NAS amphetamine produces analgesia in the formalin, but not the tail-flick test, suggests that activation of mesolimbic dopamine (DA) neurons contributes to suppression of tonic pain. Because stressors attenuate tonic pain responses, and are known to cause SP release in the VTA, we speculate that SP-induced activation of midbrain DA systems may mediate a form of pain- or stress-induced pain inhibitory system.

Combined enteral infusion of glutamine, carbohydrates, and antioxidants modulates gut protein metabolism in humans.

PubMed

Coëffier, Moïse; Claeyssens, Sophie; Lecleire, Stéphane; Leblond, Jonathan; Coquard, Aude; Bôle-Feysot, Christine; Lavoinne, Alain; Ducrotté, Philippe; Déchelotte, Pierre

2008-11-01

Available data suggest that nutrients can affect intestinal protein metabolism, which contributes to the regulation of gut barrier function. We aimed to assess whether an oral nutritional supplement (ONS) containing glutamine (as the dipeptide Ala-Gln), carbohydrates, and antioxidants would modulate duodenal protein metabolism in healthy humans. Thirty healthy control subjects were included and, over a period of 5 h, received by nasogastric tube either saline or ONS providing 11.7 kcal/kg as 0.877 g Ala-Gln/kg, 3.9 g carbohydrates/kg, and antioxidants (29.25 mg vitamin C/kg, 9.75 mg vitamin E/kg, 195 microg beta-carotene/kg, 5.85 mg Se/kg, and 390 microg Zn/kg) or glutamine (0.585 g/kg, 2.34 kcal/kg). Simultaneously, a continuous intravenous infusion of l-[1-(13)C]-leucine was done until endoscopy. Leucine enrichment was assessed by using gas chromatography-mass spectrometric analysis, and mucosal fractional synthesis rate was calculated by using intracellular amino acid enrichment as precursor. Mucosal proteolytic pathways were also evaluated. ONS infusion resulted in a doubling increase (P < 0.01) of duodenal fractional synthesis rate and a significant (P < 0.05) decrease in cathepsin D-mediated proteolysis compared with saline, whereas proteasome and Ca(2+)-dependent activities were unaffected. ONS infusion significantly (P < 0.01) decreased duodenal glutathione but not glutathione disulfide concentrations or the ratio of glutathione to glutathione disulfide. Insulinemia increased after ONS infusion, whereas plasma essential amino acids decreased. Infusion of glutamine alone did not reproduce ONS effects. ONS infusion improves duodenal protein balance in healthy humans. Further investigations are needed to study the origin of these effects and to evaluate ONS supply in stressed persons.

Role of poly-(ADP-ribose) synthetase in lipopolysaccharide-induced vascular failure and acute lung injury in pigs.

PubMed

Albertini, M; Clement, M G; Lafortuna, C L; Caniatti, M; Magder, S; Abdulmalek, K; Hussain, S N

2000-06-01

To assess the contribution of poly (adenosine 5'-diphosphate ribose) synthetase (PARS) to the development of bacterial lipopolysaccharide (LPS)-induced acute lung injury and vascular failure in pigs. Four groups of anesthetized, paralyzed, and mechanically ventilated domestic white pigs. Group 1 served as control, whereas Escherichia coli LPS (20 microg/kg/h) was continuously infused in group 2. Group 3 received 20 mg/kg injection of 3-aminobenzamide (a selective inhibitor of PARS activity) 15 minutes before LPS infusion. Only 3-aminobenzamide and not LPS was injected in group 4. All animals were examined for 180 minutes. Systemic and pulmonary hemodynamics and lung mechanics were measured during the experimental period. Lung wet/dry ratio, bronchoalveolar lavage (BAL) protein levels and cell counts and lung nitrotyrosine (footprint of peroxynitrite) immunostaining were also measured in a few animals. LPS infusion evoked a progressive decline in systemic arterial pressure, a small increase in cardiac output, and biphasic elevation of pulmonary arterial pressure. Lung compliance declined progressively, whereas lung and total respiratory resistance rose significantly after LPS infusion. Prominent nitrotyrosine immunostaining was detected around small airways and pulmonary endothelium of LPS-infused animals. No significant changes in lung wet/dry ratio and BAL protein levels and cell counts were produced by LPS infusion. Pretreatment with 3-aminobenzamide did not alter the systemic and pulmonary hemodynamic responses to LPS infusion but eliminated the rise in pulmonary and total respiratory resistance. We concluded that PARS activation plays an important role in the changes of lung mechanics associated with LPS-induced acute lung injury but had no role in vascular failure.

A dose-response study of dexmedetomidine administered as the primary sedative in infants following open heart surgery.

PubMed

Su, Felice; Nicolson, Susan C; Zuppa, Athena F

2013-06-01

To evaluate the dose-response relationship of dexmedetomidine in infants with congenital heart disease postoperative from open heart surgery. Prospective open-label dose-escalation pharmacokinetic-pharmacodynamic study. Tertiary pediatric cardiac ICU. Thirty-six evaluable infants, 1-24 months old, postoperative from open heart surgery requiring mechanical ventilation. Cohorts of 12 infants were enrolled sequentially to one of the three IV loading doses of dexmedetomidine (0.35, 0.7, and 1 mcg/kg) over 10 minutes followed by respective continuous infusions (0.25, 0.5, and 0.75 mcg/kg/hr) for up to 24 hours. Dexmedetomidine plasma concentrations were obtained at timed intervals during and following discontinuation of infusion. Pharmacodynamic variables evaluated included sedation scores, supplemental sedation and analgesia medication administration, time to tracheal extubation, respiratory function, and hemodynamic parameters. Infants achieved a deeper sedation measured by the University of Michigan Sedation Scale score (2.6 vs 1) despite requiring minimal supplemental sedation (0 unit doses/hr) and fewer analgesic medications (0.07 vs 0.15 unit doses/hr) while receiving dexmedetomidine compared with the 12-hour follow-up period. Thirty-one patients were successfully extubated while receiving the dexmedetomidine infusion. Only one patient remained intubated due to oversedation during the infusion. While receiving dexmedetomidine, there was a decrease in heart rate compared with baseline, 132 versus 161 bpm, but there was an increase in heart rate compared with postinfusion values, 132 versus 128 bpm. There was no statistically or clinically significant change in mean arterial blood pressure. Dexmedetomidine administration in infants following open heart surgery can provide improved sedation with reduction in supplemental medication requirements, leading to successful extubation while receiving a continuous infusion. The postoperative hemodynamic changes that occur in infants postoperative from open heart surgery are multifactorial. Although dexmedetomidine may play a role in decreasing heart rate immediately postoperative, the changes were not clinically significant and did not fall below postinfusion heart rates.

Doxorubicin: Comparison between 3-h continuous and bolus intravenous administration paradigms on cardio-renal axis, mitochondrial sphingolipids and pathology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kamendi, Harriet, E-mail: harriet_kamendi@kandih.com; Zhou, Ying, E-mail: yingzhou526@gmail.com; Crosby, Meredith, E-mail: Meredith.crosby@astrazeneca.com

Doxorubicin (DOX) is a potent and effective broad-spectrum anthracycline antitumor agent, but its clinical usefulness is restricted by cardiotoxicity. This study compared pharmacokinetic, functional, structural and biochemical effects of single dose DOX bolus or 3-h continuous iv infusion (3-h iv) in the Han–Wistar rat to characterize possible treatment-related differences in drug safety over a 72 h observation period. Both DOX dosing paradigms significantly altered blood pressure, core body temperature and QA interval (indirect measure of cardiac contractility); however, there was no recovery observed in the bolus iv treatment group. Following the 3-h iv treatment, blood pressures and QA interval normalizedmore » by 36 h then rose above baseline levels over 72 h. Both treatments induced biphasic changes in heart rate with initial increases followed by sustained decreases. Cardiac injury biomarkers in plasma were elevated only in the bolus iv treatment group. Tissue cardiac injury biomarkers, cardiac mitochondrial complexes I, III and V and cardiac mitochondrial sphingolipids were decreased only in the bolus iv treatment group. Results indicate that each DOX dosing paradigm deregulates sinus rhythm. However, slowing the rate of infusion allows for functional compensation of blood pressure and may decrease the likelihood of cardiac myocyte necrosis via a mechanism associated with reduced mitochondrial damage. - Highlights: • Despite damaging cardiomyocytes, continuous iv doxorubicin improves cardiovascular outcomes. • This study supports administration of doxorubicin via slow continuous iv infusion limits acute cardio-toxicity. • This study supports use of metabolomic-derived lipid biomarkers for improved quantification of cardiovascular risk. • This study supports systems-based physiological approach to generate a data that can greatly inform risk assessments.« less

Once-weekly exenatide as adjunct treatment of type 1 diabetes mellitus in patients receiving continuous subcutaneous insulin infusion therapy.

PubMed

Traina, Andrea N; Lull, Melinda E; Hui, Adrian C; Zahorian, Toni M; Lyons-Patterson, Jane

2014-08-01

The use of once-weekly exenatide in type 2 diabetes mellitus is well supported, but little is known about its effectiveness in type 1 diabetes. The objective of this study was to determine the clinical efficacy of once-weekly exenatide on glycemic control in patients with type 1 diabetes when added to basal-bolus insulin therapy. For this retrospective study, patients with type 1 diabetes, aged 18 years and older, receiving continuous subcutaneous insulin infusion, using a continuous glucose monitoring device or regularly measuring blood glucose levels and receiving 2 mg of exenatide once weekly for at least 3 months were included. Demographic information, glycated hemoglobin (A1C), body weight, body mass index, systolic and diastolic blood pressures, total daily insulin dose, basal and bolus insulin doses, 28-day continuous subcutaneous insulin infusion glucose average and incidence of hypoglycemia were collected at baseline and 3 months after beginning therapy with once-weekly exenatide. An electronic medical record search identified 11 patients with type 1 diabetes who met the inclusion criteria. Comparing baseline and 3 months after initiation of once-weekly exenatide revealed reductions of 0.6% in A1C (p=0.013), 3.7% in body weight (p=0.008), 1.7 kg/m(2) in body mass index (p=0.003), 13% in total daily insulin dose (p=0.011) and 9.3 units in bolus insulin dose (p=0.015). This study revealed that the addition of once-weekly exenatide to insulin therapy for type 1 diabetes patients leads to significant improvements in A1C, body weight, body mass index and insulin doses. Copyright © 2014 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Continuous intraperitoneal insulin infusion versus subcutaneous insulin therapy in the treatment of type 1 diabetes: effects on glycemic variability.

PubMed

van Dijk, Peter R; Groenier, Klaas H; DeVries, J Hans; Gans, Reinold O B; Kleefstra, Nanno; Bilo, Henk J G; Logtenberg, Susan J J

2015-06-01

As continuous intraperitoneal insulin infusion (CIPII) results in a more physiologic action of insulin than subcutaneous (SC) insulin administration, we hypothesized that CIPII would result in less glycemic variability (GV) than SC insulin therapy among type 1 diabetes mellitus (T1DM) patients. Data from 5-day blind continuous glucose monitoring (CGM) measurements performed during a 26-week, prospective, observational case-control study were analyzed. The coefficient of variation (CV) was the primary measure of GV. In addition, the SD of the mean glucose level, mean of daily differences, and mean amplitude of glycemic excursions were calculated. In total, 176 patients (36% male; mean age, 49 [SD 13] years; median diabetes duration, 24 [interquartile range, 17, 35] years; glycated hemoglobin level, 63 [10] mmol/mmol), of which 37 used CIPII and 139 SC insulin therapy, were analyzed. CGM data were available for 169 patients at baseline (CIPII, n=35; SC, n=134) and for 164 patients at 26 weeks (CIPII, n=35; SC, n=129). After adjustment for baseline differences, the CV was 4.9% (95% confidence interval, 1.0, 8.8) lower with CIPII- compared with SC-treated patients, irrespective of the use of multiple daily injections or continuous SC insulin infusion. There were no differences in other indices of GV between groups. Despite higher blood glucose, the CV was slightly lower with CIPII compared with SC insulin therapy in T1DM patients, and other measures of GV were identical. Future studies are needed to confirm these findings and investigate whether this results in prevention of hypoglycemia and even perhaps (less) microvascular complications.

Insulin pump use compared with intravenous insulin during labour and delivery: the INSPIRED observational cohort study.

PubMed

Drever, E; Tomlinson, G; Bai, A D; Feig, D S

2016-09-01

To assess the safety and efficacy of pump therapy (continuous subcutaneous insulin infusion; CSII) during labour and delivery in women with Type 1 diabetes. A retrospective cohort study of 161 consecutive Type 1 diabetic pregnancies delivered during 2000-2010 at Mount Sinai Hospital, Toronto, Canada. Capillary blood glucose levels during labour and delivery and time in/out of target (target: 4-6 mmol/l) were compared along with neonatal outcomes for three groups: (1) women on pumps who stayed on pumps during labour (pump/pump n = 31), (2) women on pumps who switched to intravenous (IV) insulin infusion during labour (pump/IVn = 25), and (3) women on multiple daily injections who switched to IV insulin infusion during labour (MDIn = 105). There were no significant differences between the mean or median glucose values during labour and delivery across all three groups, and no significant difference in time spent hypoglycaemic. However, women in the pump/pump group had significantly better glycaemic control as defined by mean glucose (5.5 vs. 6.4 mmol/l; P = 0.01), median glucose (5.4 vs. 6.3 mmol/l; P = 0.02), and more time spent in target (60.9% vs. 39.2%; P = 0.06) compared with women in the pump/IV group (after removing one outlier). This study demonstrates that the continuation of CSII therapy during labour and delivery appears safe and efficacious. Moreover, women who choose to continue CSII have better glucose control during delivery than those who switch to IV insulin, suggesting that it should be standard practice to allow women the option of continuing CSII during labour and delivery. © 2016 Diabetes UK.

Controlled hypotension for middle ear surgery: a comparison between remifentanil and magnesium sulphate.

PubMed

Ryu, J-H; Sohn, I-S; Do, S-H

2009-10-01

This prospective, randomized study was designed to compare remifentanil and magnesium sulphate during middle ear surgery in terms of postoperative pain and other complications. Eighty patients undergoing middle ear surgery were enrolled in the study. Patients were randomized into two groups of 40 to receive remifentanil (Group R) or magnesium sulphate (Group M) infusion. Propofol 2 mg kg(-1) was administered to induce anaesthesia, which was maintained using sevoflurane. Group R received a continuous infusion of remifentanil titrated between 3 and 4 ng ml(-1) using target-controlled infusion, whereas Group M received an i.v. magnesium sulphate bolus of 50 mg kg(-1) followed by a 15 mg kg(-1) h(-1) continuous infusion to maintain a mean arterial pressure (MAP) between 60 and 70 mm Hg. Haemodynamic variables, surgical conditions, postoperative pain, and adverse effects, such as postoperative nausea and vomiting (PONV) and shivering, were recorded. Controlled hypotension was well maintained in both groups. MAP and heart rate were higher in Group R than in Group M after operation. Surgical conditions were not different between the two groups. Postoperative pain scores were significantly lower in Group M than in Group R (P<0.05). Seventeen patients in Group R (43%) and seven patients in Group M (18%) developed PONV (P=0.01). Both magnesium sulphate and remifentanil when combined with sevoflurane provided adequate controlled hypotension and proper surgical conditions for middle ear surgery. However, patients administered magnesium sulphate had a more favourable postoperative course with better analgesia and less shivering and PONV.

Nitric oxide released by Lactobacillus farciminis improves TNBS-induced colitis in rats.

PubMed

Lamine, F; Fioramonti, J; Bueno, L; Nepveu, F; Cauquil, E; Lobysheva, I; Eutamène, H; Théodorou, V

2004-01-01

Beneficial effects of lactobacilli have been reported in experimental colitis. On the other hand, despite the controversial role of nitric oxide (NO) in the inflammatory gut process, a protective action of exogenous NO in inflammation has been suggested. Consequently, this study aimed to determine the effect of (i) sodium nitroprusside (SNP), a NO donor and (ii) treatment with Lactobacillus farciminis, which produces NO in vitro, on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats and to evaluate the role of exogenous NO in this effect. Rats were divided into three groups receiving one of the following: (i) a continuous intracolonic (IC) infusion of SNP for 4 days, (ii) L. farciminis orally for 19 days, or (iii) saline. On day 1 and day 15, respectively, TNBS and saline were administrated IC, followed by a continuous IC infusion of saline or haemoglobin, a NO scavenger. At the end of treatments, the following parameters were evaluated: macroscopic damage of colonic mucosa, myeloperoxidase and nitric oxide synthase activities and colonic luminal NO production. In colitic rats, SNP and L. farciminis treatment significantly (P < 0.05) reduced macroscopic damage scores, myeloperoxidase and nitric oxide synthase activities compared to controls. Haemoglobin infusion abolished the anti-inflammatory effect of both NO donor treatments, but had no effect per se on colitis. NO released intraluminally by SNP infusion or by L. farciminis given orally improves TNBS-induced colitis in rats. These results indicate a protective role of NO donation in colonic inflammation and show for the first time a mechanism involving NO delivery by a bacterial strain reducing an experimental colitis.

Alfaxalone for maintenance of anaesthesia in ponies undergoing field castration: continuous infusion compared with intravenous boluses.

PubMed

Deutsch, Julia; Ekiri, Abel; de Vries, Annemarie

2017-07-01

To compare alfaxalone as continuous intravenous (IV) infusion with intermittent IV injections for maintenance of anaesthesia in ponies undergoing castration. Prospective, randomized, 'blinded' clinical study. A group of 33 entire male Welsh ponies undergoing field castration. After preanaesthetic medication with IV detomidine (10 μg kg -1 ) and butorphanol (0.05 mg kg -1 ), anaesthesia was induced with IV diazepam (0.05 mg kg -1 ) followed by alfaxalone (1 mg kg -1 ). After random allocation, anaesthesia was maintained with either IV alfaxalone 2 mg kg -1  hour -1 (group A; n = 16) or saline administered at equal volume (group S; n = 17). When necessary, additional alfaxalone (0.2 mg kg -1 ) was administered IV. Ponies were breathing room air. Using simple descriptive scales, surgical conditions and anaesthesia recovery were scored. Total amount of alfaxalone, ponies requiring additional alfaxalone and time to administration, time from induction to end of infusion and end of infusion to standing were noted. Indirect arterial blood pressure, pulse and respiratory rates, end-expiratory carbon dioxide partial pressure and arterial haemoglobin oxygen saturation were recorded every 5 minutes. Data were analysed using Student t, Mann-Whitney U and chi-square tests, where appropriate (p < 0.05). Total amount of alfaxalone administered after induction of anaesthesia (0.75 ± 0.27 versus 0.17 ± 0.23 mg kg -1 ; p < 0.0001) and time to standing (14.8 ± 4 versus 11.6 ± 4 minutes; p = 0.044) were higher in group A compared to group S. Ponies requiring additional alfaxalone boluses [four (group A) versus seven (group S)] and other measured variables were similar between groups; five ponies required oxygen supplementation [three (group A) versus two (group S)]. Continuous IV infusion and intermittent administration of alfaxalone provided similar anaesthesia quality and surgical conditions in ponies undergoing field castration. Less alfaxalone is required when used intermittently. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

Effects of exposure to simulated microgravity on neuronal catecholamine release and blood pressure responses to norepinephrine and angiotensin

NASA Technical Reports Server (NTRS)

Convertino, V. A.; Ludwig, D. A.; Gray, B. D.; Vernikos, J.

1998-01-01

We tested the hypothesis that exposure to microgravity reduces the neuronal release of catecholamines and blood pressure responses to norepinephrine and angiotensin. Eight men underwent 30 days of 6 degrees head-down tilt (HDT) bedrest to simulate exposure to microgravity. Plasma norepinephrine and mean arterial blood pressure (MAP) were measured before and after a cold pressor test (CPT) and graded norepinephrine infusion (8, 16 and 32 ng/kg/min) on day 6 of a baseline control period (C6) and on days 14 and 27 of HDT. MAP and plasma angiotensin II (Ang-II) were measured during graded Ang-II infusion (1, 2 and 4 ng/kg/min) on C8 and days 16 and 29 of HDT. Baseline total circulating norepinephrine was reduced from 1017ng during the baseline control period to 610 ng at day 14 and 673ng at day 27 of HDT, confirming a hypoadrenergic state. An elevation of norepinephrine (+178 ng) to the CPT during the baseline control period was eliminated by HDT days 14 and 27. During norepinephrine infusion, similar elevations in plasma norepinephrine (7.7 pg/ml/ng/kg/min) caused similar elevations in MAP (0.12 mmHg/ng/kg/min) across all test days. Ang-II infusion produced higher levels of plasma Ang-II during HDT (47.3 pg/ml) than during baseline control (35.5 pg/ml), while producing similar corresponding elevations in blood pressure. While vascular responsiveness to norepinephrine appears unaffected, impaired neuronal release of norepinephrine and reduced vascular responsiveness to Ang-II might contribute to the lessened capacity to vasoconstrict after spaceflight. The time course of alterations indicates effects that occur within two weeks of exposure.

Murine intracochlear drug delivery: reducing concentration gradients within the cochlea.

PubMed

Borkholder, David A; Zhu, Xiaoxia; Hyatt, Brad T; Archilla, Alfredo S; Livingston, William J; Frisina, Robert D

2010-09-01

Direct delivery of compounds to the mammalian inner ear is most commonly achieved by absorption or direct injection through the round window membrane (RWM), or infusion through a basal turn cochleostomy. These methods provide direct access to cochlear structures, but with a strong basal-to-apical concentration gradient consistent with a diffusion-driven distribution. This gradient limits the efficacy of therapeutic approaches for apical structures, and puts constraints on practical therapeutic dose ranges. A surgical approach involving both a basal turn cochleostomy and a posterior semicircular canal canalostomy provides opportunities for facilitated perfusion of cochlear structures to reduce concentration gradients. Infusion of fixed volumes of artificial perilymph (AP) and sodium salicylate were used to evaluate two surgical approaches in the mouse: cochleostomy-only (CO), or cochleostomy-plus-canalostomy (C+C). Cochlear function was evaluated via closed-system distortion product otoacoustic emissions (DPOAE) threshold level measurements from 8 to 49 kHz. AP infusion confirmed no surgical impact to auditory function, while shifts in DPOAE thresholds were measured during infusion of salicylate and AP (washout). Frequency dependent shifts were compared for the CO and C+C approaches. Computer simulations modeling diffusion, volume flow, interscala transport, and clearance mechanisms provided estimates of drug concentration as a function of cochlear position. Simulated concentration profiles were compared to frequency-dependent shifts in measured auditory responses using a cochlear tonotopic map. The impact of flow rate on frequency dependent DPOAE threshold shifts was also evaluated for both surgical approaches. Both the C+C approach and a flow rate increase were found to provide enhanced response for lower frequencies, with evidence suggesting the C+C approach reduces concentration gradients within the cochlea. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Murine Intracochlear Drug Delivery: Reducing Concentration Gradients within the Cochlea

PubMed Central

Borkholder, David A.; Zhu, Xiaoxia; Hyatt, Brad T.; Archilla, Alfredo S.; Livingston, William J.; Frisina, Robert D.

2010-01-01

Direct delivery of compounds to the mammalian inner ear is most commonly achieved by absorption or direct injection through the round window membrane (RWM), or infusion through a basal turn cochleostomy. These methods provide direct access to cochlear structures, but with a strong basal-to-apical concentration gradient consistent with a diffusion-driven distribution. This gradient limits the efficacy of therapeutic approaches for apical structures, and puts constraints on practical therapeutic dose ranges. A surgical approach involving both a basal turn cochleostomy and a posterior semicircular canal canalostomy provides opportunities for facilitated perfusion of cochlear structures to reduce concentration gradients. Infusion of fixed volumes of artificial perilymph (AP) and sodium salicylate were used to evaluate two surgical approaches in the mouse: cochleostomy-only (CO), or cochleostomy-plus-canalostomy (C+C). Cochlear function was evaluated via closed-system distortion product otoacoustic emissions (DPOAE) threshold level measurements from 8-49 kHz. AP infusion confirmed no surgical impact to auditory function, while shifts in DPOAE thresholds were measured during infusion of salicylate and AP (washout). Frequency dependent shifts were compared for the CO and C+C approaches. Computer simulations modeling diffusion, volume flow, interscala transport, and clearance mechanisms provided estimates of drug concentration as a function of cochlear position. Simulated concentration profiles were compared to frequency-dependent shifts in measured auditory responses using a cochlear tonotopic map. The impact of flow rate on frequency dependent DPOAE threshold shifts was also evaluated for both surgical approaches. Both the C+C approach and a flow rate increase were found to provide enhanced response for lower frequencies, with evidence suggesting the C+C approach reduces concentration gradients within the cochlea. PMID:20451593

Subanesthetic, Subcutaneous Ketamine Infusion Therapy in the Treatment of Chronic Nonmalignant Pain.

PubMed

Zekry, Olfat; Gibson, Stephen B; Aggarwal, Arun

2016-06-01

This study was designed to describe the efficacy and toxicity of subcutaneous ketamine infusions and sublingual ketamine lozenges for the treatment of chronic nonmalignant pain. Data were collected prospectively on 70 subjects managed in an academic, tertiary care hospital between 2007 and 2012 who received between 3 and 7 days of subanesthetic, subcutaneous ketamine infusion. Data were analyzed for efficacy, adverse effects, and reduction in use of opioid medication. We also analyzed whether subsequent treatment with sublingual ketamine lozenges resulted in longer-term efficacy of the beneficial effects of the initial ketamine infusion. There was a significant reduction in pain intensity measured by numerical rating scale (NRS) from mean of 6.38 before ketamine to 4.60 after ketamine (P < .005) that was sustained for between 3 months and 6 years. In subjects on opioids, there was a significant reduction in opioid use at the end of the ketamine infusion from a mean morphine equivalent dose (MMED) of 216 mg/day before ketamine to 89 mg/day after ketamine (P < .005). The overall reduction in opioid use after ketamine infusion was 59%. No subjects increased their use of opioids during their hospitalization for the ketamine infusion. A small proportion of subjects who responded to the infusion were continued on ketamine lozenges. This group was followed for between 3 months and 2 years. The use of ketamine lozenges after the infusion resulted in 31% of these subjects being able to cease their use of opioids compared with only 6% who did not receive ketamine lozenges. Eleven percent of subjects who received lozenges subsequently increased their opioid usage. Adverse effects were fairly common, but only mild, with 46% of patients experiencing light-headedness and dizziness, 25% tiredness and sedation, 12% headaches, 12% hallucinations, and 8% vivid dreams. Adverse effects were easily managed by reducing the rate of the ketamine infusion. The administration of subanesthetic, subcutaneous ketamine infusion was well tolerated, with mostly mild adverse effects and no serious adverse effects. The infusion provided significant pain relief in subjects who had failed a wide range of pharmacological and cognitive behavioral therapies. In addition, the results indicate that sublingual ketamine lozenges offer a promising therapeutic option for longer-term relief of chronic nonmalignant pain. The ketamine lozenges have been shown to have acceptable storage stability, and the sublingual bioavailability is sufficiently high and reproducible to support its use in this context.

A physiological increase in the hepatic glycogen level does not affect the response of net hepatic glucose uptake to insulin.

PubMed

Winnick, Jason J; An, Zhibo; Moore, Mary Courtney; Ramnanan, Christopher J; Farmer, Ben; Shiota, Masakazu; Cherrington, Alan D

2009-08-01

To determine the effect of an acute increase in hepatic glycogen on net hepatic glucose uptake (NHGU) and disposition in response to insulin in vivo, studies were performed on two groups of dogs fasted 18 h. During the first 4 h of the study, somatostatin was infused peripherally, while insulin and glucagon were replaced intraportally in basal amounts. Hyperglycemia was brought about by glucose infusion, and either saline (n = 7) or fructose (n = 7; to stimulate NHGU and glycogen deposition) was infused intraportally. A 2-h control period then followed, during which the portal fructose and saline infusions were stopped, allowing NHGU and glycogen deposition in the fructose-infused animals to return to rates similar to those of the animals that received the saline infusion. This was followed by a 2-h experimental period, during which hyperglycemia was continued but insulin infusion was increased fourfold in both groups. During the initial 4-h glycogen loading period, NHGU averaged 1.18 +/- 0.27 and 5.55 +/- 0.53 mg x kg(-1) x min(-1) and glycogen synthesis averaged 0.72 +/- 0.24 and 3.98 +/- 0.57 mg x kg(-1) x min(-1) in the saline and fructose groups, respectively (P < 0.05). During the 2-h hyperinsulinemic period, NHGU rose from 1.5 +/- 0.4 and 0.9 +/- 0.2 to 3.1 +/- 0.6 and 2.5 +/- 0.5 mg x kg(-1) x min(-1) in the saline and fructose groups, respectively, a change of 1.6 mg x kg(-1) x min(-1) in both groups despite a significantly greater liver glycogen level in the fructose-infused group. Likewise, the metabolic fate of the extracted glucose (glycogen, lactate, or carbon dioxide) was not different between groups. These data indicate that an acute physiological increase in the hepatic glycogen content does not alter liver glucose uptake and storage under hyperglycemic/hyperinsulinemic conditions in the dog.

Effects of Dopamine Donor Pretreatment on Graft Survival after Kidney Transplantation: A Randomized Trial.

PubMed

Schnuelle, Peter; Schmitt, Wilhelm H; Weiss, Christel; Habicht, Antje; Renders, Lutz; Zeier, Martin; Drüschler, Felix; Heller, Katharina; Pisarski, Przemyslaw; Banas, Bernhard; Krämer, Bernhard K; Jung, Matthias; Lopau, Kai; Olbricht, Christoph J; Weihprecht, Horst; Schenker, Peter; De Fijter, Johan W; Yard, Benito A; Benck, Urs

2017-03-07

Donor dopamine improves initial graft function after kidney transplantation due to antioxidant properties. We investigated if a 4 µ g/kg per minute continuous dopamine infusion administered after brain-death confirmation affects long-term graft survival and examined the exposure-response relationship with treatment duration. Five-year follow-up of 487 renal transplant patients from 60 European centers who had participated in the randomized, multicenter trial of dopamine donor pretreatment between 2004 and 2007 (ClinicalTrials.gov identifier: NCT00115115). Follow-up was complete in 99.2%. Graft survival was 72.6% versus 68.7% ( P =0.34), and 83.3% versus 80.4% ( P =0.42) after death-censoring in treatment and control arms according to trial assignment. Although infusion times varied substantially in the treatment arm (range 0-32.2 hours), duration of the dopamine infusion and all-cause graft failure exhibited an exposure-response relationship (hazard ratio, 0.96; 95% confidence interval [95% CI], 0.92 to 1.00, per hour). Cumulative frequency curves of graft survival and exposure time of the dopamine infusion indicated a maximum response rate at 7.10 hours (95% CI, 6.99 to 7.21), which almost coincided with the optimum infusion time for improvement of early graft function (7.05 hours; 95% CI, 6.92 to 7.18). Taking infusion time of 7.1 hours as threshold in subsequent graft survival analyses indicated a relevant benefit: Overall, 81.5% versus 68.5%; P =0.03; and 90.3% versus 80.2%; P =0.04 after death-censoring. We failed to show a significant graft survival advantage on intention-to-treat. Dopamine infusion time was very short in a considerable number of donors assigned to treatment. Our finding of a significant, nonlinear exposure-response relationship disclosed a threshold value of the dopamine infusion time that may improve long-term kidney graft survival. Copyright © 2017 by the American Society of Nephrology.

Interrupted intracarotid artery cold saline infusion as an alternative method for neuroprotection after ischemic stroke.

PubMed

Ji, Ya-Bin; Wu, Yong-Ming; Ji, Zhong; Song, Wei; Xu, Sui-Yi; Wang, Yao; Pan, Su-Yue

2012-07-01

Intracarotid artery cold saline infusion (ICSI) is an effective method for protecting brain tissue, but its use is limited because of undesirable secondary effects, such as severe decreases in hematocrit levels, as well as its relatively brief duration. In this study, the authors describe and investigate the effects of a novel ICSI pattern (interrupted ICSI) relative to the traditional method (uninterrupted ICSI). Ischemic strokes were induced in 85 male Sprague-Dawley rats by occluding the middle cerebral artery for 3 hours using an intraluminal filament. Uninterrupted infusion groups received an infusion at 15 ml/hour for 30 minutes continuously. The same infusion speed was used in the interrupted infusion groups, but the whole duration was divided into trisections, and there was a 20-minute interval without infusion between sections. Forty-eight hours after reperfusion, H & E and silver nitrate staining were utilized for morphological assessment. Infarct sizes and brain water contents were determined using H & E staining and the dry-wet weight method, respectively. Levels of neuron-specific enolase (NSE), S100β protein, and matrix metalloproteinase 9 (MMP-9) in the serum were determined using enzyme-linked immunosorbent assay. Neurological deficits were also evaluated. Histology showed that interrupted ICSI did not affect neurons or fibers in rat brains, which suggests that this method is safe for brain tissues with ischemia. The duration of hypothermia induced by interrupted ICSI was longer than that induced via the traditional method, and the decrease in hematocrit levels was less pronounced. There were no differences in infarct size or brain water content between uninterrupted and interrupted ICSI groups, but neuron-specific enolase and matrix metalloproteinase 9 serum levels were more reduced after interrupted ICSI than after the traditional method. Interrupted ICSI is a safe method. Compared with traditional ICSI, the interrupted method has a longer duration of hypothermia and less effect on hematocrit and offers more potentially improved neuroprotection, thereby making it more attractive as an infusion technique in the clinic.

Model-Driven Safety Analysis of Closed-Loop Medical Systems

PubMed Central

Pajic, Miroslav; Mangharam, Rahul; Sokolsky, Oleg; Arney, David; Goldman, Julian; Lee, Insup

2013-01-01

In modern hospitals, patients are treated using a wide array of medical devices that are increasingly interacting with each other over the network, thus offering a perfect example of a cyber-physical system. We study the safety of a medical device system for the physiologic closed-loop control of drug infusion. The main contribution of the paper is the verification approach for the safety properties of closed-loop medical device systems. We demonstrate, using a case study, that the approach can be applied to a system of clinical importance. Our method combines simulation-based analysis of a detailed model of the system that contains continuous patient dynamics with model checking of a more abstract timed automata model. We show that the relationship between the two models preserves the crucial aspect of the timing behavior that ensures the conservativeness of the safety analysis. We also describe system design that can provide open-loop safety under network failure. PMID:24177176

Model-Driven Safety Analysis of Closed-Loop Medical Systems.

PubMed

Pajic, Miroslav; Mangharam, Rahul; Sokolsky, Oleg; Arney, David; Goldman, Julian; Lee, Insup

2012-10-26

In modern hospitals, patients are treated using a wide array of medical devices that are increasingly interacting with each other over the network, thus offering a perfect example of a cyber-physical system. We study the safety of a medical device system for the physiologic closed-loop control of drug infusion. The main contribution of the paper is the verification approach for the safety properties of closed-loop medical device systems. We demonstrate, using a case study, that the approach can be applied to a system of clinical importance. Our method combines simulation-based analysis of a detailed model of the system that contains continuous patient dynamics with model checking of a more abstract timed automata model. We show that the relationship between the two models preserves the crucial aspect of the timing behavior that ensures the conservativeness of the safety analysis. We also describe system design that can provide open-loop safety under network failure.

Infusing and selecting V&V activities

NASA Technical Reports Server (NTRS)

Feather, M. S.

2002-01-01

The evolving nature of software development poses a continuing series of challenges for V&V. In response, the V&V community selectively adapts the use of existing V&V activities, and introduces new and improved ones.

Improved usability of a multi-infusion setup using a centralized control interface: A task-based usability test

PubMed Central

Cnossen, Fokie; Dieperink, Willem; Bult, Wouter; de Smet, Anne Marie; Touw, Daan J.; Nijsten, Maarten W.

2017-01-01

The objective of this study was to assess the usability benefits of adding a bedside central control interface that controls all intravenous (IV) infusion pumps compared to the conventional individual control of multiple infusion pumps. Eighteen dedicated ICU nurses volunteered in a between-subjects task-based usability test. A newly developed central control interface was compared to conventional control of multiple infusion pumps in a simulated ICU setting. Task execution time, clicks, errors and questionnaire responses were evaluated. Overall the central control interface outperformed the conventional control in terms of fewer user actions (40±3 vs. 73±20 clicks, p<0.001) and fewer user errors (1±1 vs. 3±2 errors, p<0.05), with no difference in task execution times (421±108 vs. 406±119 seconds, not significant). Questionnaires indicated a significant preference for the central control interface. Despite being novice users of the central control interface, ICU nurses displayed improved performance with the central control interface compared to the conventional interface they were familiar with. We conclude that the new user interface has an overall better usability than the conventional interface. PMID:28800617

Optimal intravenous infusion to decrease the haematocrit level in patient of DHF infection

NASA Astrophysics Data System (ADS)

Handayani, D.; Nuraini, N.; Saragih, R.; Wijaya, K. P.; Naiborhu, J.

2014-02-01

The optimal control of infusion model for Dengue Hemorrhagic Fever (DHF) infection is formulated here. The infusion model will be presented in form of haematocrit level. The input control aim to normalize the haematocrit level and is expressed as infusion volume on mL/day. The stability near the equilibrium points will be analyzed. Numerical simulation shows the dynamic of each infection compartments which gives a description of within-host dynamic of dengue virus. These results show particularly that infected compartments tend to be vanished in ±15days after the onset of the virus. In fact, without any control added, the haematocrit level will decrease but not up to the normal level. Therefore the effective haematocrit normalization should be done with the treatment control. Control treatment for a fixed time using a control input can bring haematocrit level to normal range 42-47%. The optimal control in this paper is divided into three cases, i.e. fixed end point, constrained input, and tracking haematocrit state. Each case shows different infection condition in human body. However, all cases require that the haematocrit level to be in normal range in fixed final time.

Improved usability of a multi-infusion setup using a centralized control interface: A task-based usability test.

PubMed

Doesburg, Frank; Cnossen, Fokie; Dieperink, Willem; Bult, Wouter; de Smet, Anne Marie; Touw, Daan J; Nijsten, Maarten W

2017-01-01

The objective of this study was to assess the usability benefits of adding a bedside central control interface that controls all intravenous (IV) infusion pumps compared to the conventional individual control of multiple infusion pumps. Eighteen dedicated ICU nurses volunteered in a between-subjects task-based usability test. A newly developed central control interface was compared to conventional control of multiple infusion pumps in a simulated ICU setting. Task execution time, clicks, errors and questionnaire responses were evaluated. Overall the central control interface outperformed the conventional control in terms of fewer user actions (40±3 vs. 73±20 clicks, p<0.001) and fewer user errors (1±1 vs. 3±2 errors, p<0.05), with no difference in task execution times (421±108 vs. 406±119 seconds, not significant). Questionnaires indicated a significant preference for the central control interface. Despite being novice users of the central control interface, ICU nurses displayed improved performance with the central control interface compared to the conventional interface they were familiar with. We conclude that the new user interface has an overall better usability than the conventional interface.

Six Reasons To Infuse Science with Technology.

ERIC Educational Resources Information Center

Devitt, Terry

1997-01-01

Discusses six ways in which technology is transforming science education in classrooms across America. Discusses jet fuel for science reform, access to inaccessible worlds, thinking like scientists, turning data into pictures, exploration through simulation, and bringing teachers up to speed. (JRH)

Measurements of evaporated perfluorocarbon during partial liquid ventilation by a zeolite absorber.

PubMed

Proquitté, Hans; Rüdiger, Mario; Wauer, Roland R; Schmalisch, Gerd

2004-01-01

During partial liquid ventilation (PLV) the knowledge of the quantity of exhaled perfluorocarbon (PFC) allows a continuous substitution of the PFC loss to achieve a constant PFC level in the lungs. The aim of our in vitro study was to determine the PFC loss in the mixed expired gas by an absorber and to investigate the effect of the evaporated PFC on ventilatory measurements. To simulate the PFC loss during PLV, a heated flask was rinsed with a constant airflow of 4 L min(-1) and PFC was infused by different speeds (5, 10, 20 mL h(-1)). An absorber filled with PFC selective zeolites was connected with the flask to measure the PFC in the gas. The evaporated PFC volume and the PFC concentration were determined from the weight gain of the absorber measured by an electronic scale. The PFC-dependent volume error of the CO2SMO plus neonatal pneumotachograph was measured by manual movements of a syringe with volumes of 10 and 28 mL with a rate of 30 min(-1). Under steady state conditions there was a strong correlation (r2 = 0.999) between the infusion speed of PFC and the calculated PFC flow rate. The PFC flow rate was slightly underestimated by 4.3% (p < 0.01). However, this bias was independent from PFC infusion rate. The evaporated PFC volume was precisely measured with errors < 1%. The volume error of the CO2SMO-Plus pneumotachograph increased with increasing PFC content for both tidal volumes (p < 0.01). However for PFC flow rates up to 20 mL/h the error of the measured tidal volumes was < 5%. PFC selective zeolites can be used to quantify accurately the evaporated PFC volume during PLV. With increasing PFC concentrations in the exhaled air the measurement errors of ventilatory parameters have to be taken into account.

Continuation of Employment Training for Students in the Shell Fisheries Industry. Final Report. 1981-1982.

ERIC Educational Resources Information Center

Cape May County Vocational Schools, NJ.

A project to provide training in the shell fishing industries was continued into its second year to develop entry-level skills for employment and provide instruction and hands-on experience through infusing the existing Marine Science program. Results from a survey of instructors and individuals involved in the industry were used to develop a…

[A mathematic analysis of different manners of replacement fluid infusion in continuous veno-venous hemofiltration].

PubMed

Wu, Yunzhen; Wang, Chunting

2015-05-01

To establish a mathematical formula for choosing the manner of replacement fluid infusion in continuous renal replacement therapy (CRRT), so as to provide the basis for improving the treatment effect. A mathematical formula for choosing the manner of replacement fluid infusion with continuous veno-venous hemofiltration (CVVH) was taken as an example, and it was compared with the result of standard replacement fluid in order to analyze the effect of different manners of infusion. (1) Comparison parameters: the plasma volume ("Vreturn") and some electrolyte concentration ("Creturn") in back way of CRRT ( if other thing was solute, filter coefficient should be 1.0). (2) Research objects: the actual replacement fluid (for example, the most complex should be sorted into A and B type) mode (pre or post) was compared with the standard replacement fluid (the A and B in one). (3) Based on the formula of standard replacement, four equations in different conditions were derived: pre-dilution and post-dilution mode; same direction and same ratio; same direction and different ratio; different direction and same ratio; different direction and different ratio. The calculated results of "Vreturn" (except hematocrit) and "Creturn" were same to the standard only following the rule of same direction and ratio for A and B no matter pre-dilution mode or post-dilution mode, and it was different from the standard in others. In pre-dilution mode and post-dilution mode, it showed: (1) A and B in same direction and different ratio: "Vreturn" and "Creturn" were different from the standard for the alterative ratio of B. (2) A and B in different direction and same ratio: "Vreturn" was same to the standard, but "Creturn" was different from the standard for the completely different and more complex computational formula. (3) A and B in different direction and different ratio: both "Vreturn" and "Creturn" were different from the standard. The different "Vreturn" was due to the different ratio of B. The different "Creturn" was caused by different ratio of B and the completely different computational formula. (1) For parts of replacement fluid which must be separated (for example, bicarbonate formula), the result is same to the standard, and is predicted and mastered only following the rule of same direction and ratio. Otherwise, we need to calculate the two parameters over and over again. The result will run out of our judgment. The wrongness of losing water and electrolyte disorders maybe come out. (2) Accordingly,the formula could be used to analyze the same case like the separated replacement infusion, for example, a large number of citrates as regional anticoagulation were infused only in the front of filter, while the replacement fluid can be done in varied forms.

Prolonged continuous intravenous infusion of the dipeptide L-alanine- L-glutamine significantly increases plasma glutamine and alanine without elevating brain glutamate in patients with severe traumatic brain injury

PubMed Central

2014-01-01

Introduction Low plasma glutamine levels are associated with worse clinical outcome. Intravenous glutamine infusion dose- dependently increases plasma glutamine levels, thereby correcting hypoglutaminemia. Glutamine may be transformed to glutamate which might limit its application at a higher dose in patients with severe traumatic brain injury (TBI). To date, the optimal glutamine dose required to normalize plasma glutamine levels without increasing plasma and cerebral glutamate has not yet been defined. Methods Changes in plasma and cerebral glutamine, alanine, and glutamate as well as indirect signs of metabolic impairment reflected by increased intracranial pressure (ICP), lactate, lactate-to-pyruvate ratio, electroencephalogram (EEG) activity were determined before, during, and after continuous intravenous infusion of 0.75 g L-alanine-L-glutamine which was given either for 24 hours (group 1, n = 6) or 5 days (group 2, n = 6) in addition to regular enteral nutrition. Lab values including nitrogen balance, urea and ammonia were determined daily. Results Continuous L-alanine-L-glutamine infusion significantly increased plasma and cerebral glutamine as well as alanine levels, being mostly sustained during the 5 day infusion phase (plasma glutamine: from 295 ± 62 to 500 ± 145 μmol/ l; brain glutamine: from 183 ± 188 to 549 ± 120 μmol/ l; plasma alanine: from 327 ± 91 to 622 ± 182 μmol/ l; brain alanine: from 48 ± 55 to 89 ± 129 μmol/ l; p < 0.05, ANOVA, post hoc Dunn’s test). Plasma glutamate remained unchanged and cerebral glutamate was decreased without any signs of cerebral impairment. Urea and ammonia were significantly increased within normal limits without signs of organ dysfunction (urea: from 2.7 ± 1.6 to 5.5 ± 1.5 mmol/ l; ammonia: from 12 ± 6.3 to 26 ± 8.3 μmol/ l; p < 0.05, ANOVA, post hoc Dunn’s test). Conclusions High dose L-alanine-L-glutamine infusion (0.75 g/ kg/ d up to 5 days) increased plasma and brain glutamine and alanine levels. This was not associated with elevated glutamate or signs of potential glutamate-mediated cerebral injury. The increased nitrogen load should be considered in patients with renal and hepatic dysfunction. Trial registration Clinicaltrials.gov NCT02130674. Registered 5 April 2014 PMID:24992948

Pseudoaneurysm embolization and vasopressin infusion for lower gastrointestinal bleeding due to recurrence of urinary bladder carcinoma.

PubMed

Kakizawa, Hideaki; Toyota, Naoyuki; Mita, Koji; Fujimura, Yoshio; Hieda, Masashi; Hirai, Nobuhiko; Tachikake, Toshihiro; Ito, Katsuhide

2006-05-01

We report a case that was successfully treated for massive lower gastrointestinal (LGI) bleeding due to a recurrent urinary bladder carcinoma. Treatment consisted of combination therapy including embolization of an inferior gluteal artery (IGA) pseudoaneurysm and low-dose arterial vasopressin infusion via a sigmoid artery (SA). A 57-year-old man presented with life-threatening sudden, massive LGI bleeding due to an obturator lymph node (LN) metastasis from a urinary bladder carcinoma. Computed tomography showed that the LN recurrence had invaded all the way to the sigmoid colon, and there was a pseudoaneurysm with extravasation inside the recurrence. An angiogram revealed a left IGA pseudoaneurysm. We therefore excluded the pseudoaneurysm by embolization with microcoils. Following this treatment the bleeding decreased, but intermittent LGI bleeding continued. Endoscopic examination showed the tumor with a huge ulcer inside the colonic lumen, and continuous oozing was confirmed. A second angiogram showed no recurrence of the IGA pseudoaneurysm and no apparent findings of bleeding. Then a 3F microcatheter was placed in the SA selectively using a coaxial catheter system, and vasopressin was infused at a rate 0.05 U/min for 12 h. Bleeding completely ceased 2 days later. There were no signs of ischemic gastrointestinal complications. Massive LGI bleeding has not recurred in 5 months.

The Effect of Milrinone on the Right Ventriclular Function in Patients with Reduced Right Ventricular Function Undergoing Off-pump Coronary Artery Bypass Graft Surgery

PubMed Central

Lee, Jong Hwa; Oh, Young Jun; Shim, Yon Hee; Hong, Yong Woo; Yi, Gijong

2006-01-01

This investigation evaluated the effect of continuous milrinone infusion on right ventriclular (RV) function during off-pump coronary artery bypass graft (OPCAB) surgery in patients with reduced RV function. Fifty patients scheduled for OPCAB, with thermodilution RV ejection fraction (RVEF) <35% after anesthesia induction, were randomly allocated to either milrinone (0.5 µg/kg/min) or control (saline) group. Hemodynamic variables and RV volumetric data measured by thermodilution method were collected as follows: after anesthesia induction (T1); 10 min after heart displacement for obtuse marginal artery anastomosis (T2); after pericardial closure (T3). Cardiac index and heart rate increased and systemic vascular resistance significantly decreased in milrinone group at T2. Initially lower RVEF of milrinone group was eventually comparable to control group after milrinone infusion. RVEF did not significantly change at T2 and T3 in both groups. RV end-diastolic volume in milrinone group consistently decreased from the baseline at T2 and T3. Continuous infusion of milrinone without a bolus demonstrated potentially beneficial effect on cardiac output and RV afterload in patients with reduced RV function during OPCAB. However, aggressive augmentation of intravascular volume seems to be necessary to maximize the effect of the milrinone in these patients. PMID:17043419

Pharmacokinetics of Colistin Methansulphonate (CMS) and Colistin after CMS Nebulisation in Baboon Monkeys.

PubMed

Marchand, Sandrine; Bouchene, Salim; de Monte, Michèle; Guilleminault, Laurent; Montharu, Jérôme; Cabrera, Maria; Grégoire, Nicolas; Gobin, Patrice; Diot, Patrice; Couet, William; Vecellio, Laurent

2015-10-01

The objective of this study was to compare two different nebulizers: Eflow rapid® and Pari LC star® by scintigraphy and PK modeling to simulate epithelial lining fluid concentrations from measured plasma concentrations, after nebulization of CMS in baboons. Three baboons received CMS by IV infusion and by 2 types of aerosols generators and colistin by subcutaneous infusion. Gamma imaging was performed after nebulisation to determine colistin distribution in lungs. Blood samples were collected during 9 h and colistin and CMS plasma concentrations were measured by LC-MS/MS. A population pharmacokinetic analysis was conducted and simulations were performed to predict lung concentrations after nebulization. Higher aerosol distribution into lungs was observed by scintigraphy, when CMS was nebulized with Pari LC® star than with Eflow Rapid® nebulizer. This observation was confirmed by the fraction of CMS deposited into the lung (respectively 3.5% versus 1.3%).CMS and colistin simulated concentrations in epithelial lining fluid were higher after using the Pari LC star® than the Eflow rapid® system. A limited fraction of CMS reaches lungs after nebulization, but higher colistin plasma concentrations were measured and higher intrapulmonary colistin concentrations were simulated with the Pari LC Star® than with the Eflow Rapid® system.

Drugs given by a syringe driver: a prospective multicentre survey of palliative care services in the UK.

PubMed

Wilcock, Andrew; Jacob, Jayin K; Charlesworth, Sarah; Harris, Elayne; Gibbs, Margaret; Allsop, Helen

2006-10-01

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.

Propofol-Related Infusion Syndrome in Critically Ill Pediatric Patients: Coincidence, Association, or Causation?

PubMed Central

Timpe, Erin M.; Eichner, Samantha F.; Phelps, Stephanie J.

2006-01-01

Over the past two decades numerous reports have described the development of a propofol-related infusion syndrome (PRIS) in critically ill adult and pediatric patients who received continuous infusion propofol for anesthesia or sedation. The syndrome is generally characterized by progressive metabolic acidosis, hemodynamic instability and bradyarrhythmias that are refractory to aggressive pharmacological treatments. PRIS may occur with or without the presence of hepatomegaly, rhabdomyolysis or lipemia. To date, the medical literature contains accounts of 20 deaths in critically ill pediatric patients who developed features consistent with PRIS. These reports have generated considerable discussion and debate regarding the relationship, if any, between propofol and a constellation of clinical symptoms and features that have been attributed to its use in critically ill pediatric patients. This paper reviews the literature concerning PRIS, its clinical presentation, proposed mechanisms for the syndrome, and potential management should the syndrome occur. PMID:23118644

Infusing Software Assurance Research Techniques into Use

NASA Technical Reports Server (NTRS)

Pressburger, Thomas; DiVito, Ben; Feather, Martin S.; Hinchey, Michael; Markosian, Lawrence; Trevino, Luis C.

2006-01-01

Research in the software engineering community continues to lead to new development techniques that encompass processes, methods and tools. However, a number of obstacles impede their infusion into software development practices. These are the recurring obstacles common to many forms of research. Practitioners cannot readily identify the emerging techniques that may benefit them, and cannot afford to risk time and effort evaluating and trying one out while there remains uncertainty about whether it will work for them. Researchers cannot readily identify the practitioners whose problems would be amenable to their techniques, and, lacking feedback from practical applications, are hard-pressed to gauge the where and in what ways to evolve their techniques to make them more likely to be successful. This paper describes an ongoing effort conducted by a software engineering research infusion team established by NASA s Software Engineering Initiative to overcome these obstacles. .

An Invitation to the Dance: From Dragons to Wolves.

ERIC Educational Resources Information Center

Berube', Barney

1992-01-01

Multicultural education occurs in environments that consciously recognize the existence of racism, celebrate all cultures, infuse diversity in the curriculum, make it a continuous spiraling process, encourage critical thinking, and seek reform and change. (SK)

Levofloxacin Cures Experimental Pneumonic Plague in African Green Monkeys

PubMed Central

McDonald, Jacob D.; Brasel, Trevor L.; Barr, Edward B.; Gigliotti, Andrew P.; Koster, Frederick

2011-01-01

Background Yersinia pestis, the agent of plague, is considered a potential bioweapon due to rapid lethality when delivered as an aerosol. Levofloxacin was tested for primary pneumonic plague treatment in a nonhuman primate model mimicking human disease. Methods and Results Twenty-four African Green monkeys (AGMs, Chlorocebus aethiops) were challenged via head-only aerosol inhalation with 3–145 (mean = 65) 50% lethal (LD50) doses of Y. pestis strain CO92. Telemetered body temperature >39°C initiated intravenous infusions to seven 5% dextrose controls or 17 levofloxacin treated animals. Levofloxacin was administered as a “humanized” dose regimen of alternating 8 mg/kg and 2 mg/kg 30-min infusions every 24-h, continuing until animal death or 20 total infusions, followed by 14 days of observation. Fever appeared at 53–165 h and radiographs found multilobar pneumonia in all exposed animals. All control animals died of severe pneumonic plague within five days of aerosol exposure. All 16 animals infused with levofloxacin for 10 days survived. Levofloxacin treatment abolished bacteremia within 24 h in animals with confirmed pre-infusion bacteremia, and reduced tachypnea and leukocytosis but not fever during the first 2 days of infusions. Conclusion Levofloxacin cures established pneumonic plague when treatment is initiated after the onset of fever in the lethal aerosol-challenged AGM nonhuman primate model, and can be considered for treatment of other forms of plague. Levofloxacin may also be considered for primary presumptive-use, multi-agent antibiotic in bioterrorism events prior to identification of the pathogen. PMID:21347450

Inhaled nitrite reverses hemolysis-induced pulmonary vasoconstriction in newborn lambs without blood participation

PubMed Central

Blood, Arlin B.; Schroeder, Hobe J.; Terry, Michael H.; Merrill-Henry, Jeanette; Bragg, Shannon L.; Vrancken, Kurt; Liu, Taiming; Herring, Jason L.; Sowers, Lawrence C.; Wilson, Sean M.; Power, Gordon G.

2011-01-01

Background Nitrite can be converted to nitric oxide (NO) by a number of different biochemical pathways. In newborn lambs an aerosol of inhaled nitrite has been found to reduce pulmonary blood pressure, possibly acting via conversion to NO by reaction with intraerythrocytic deoxyhemoglobin. If so, the vasodilating effects of nitrite would be attenuated by free hemoglobin in plasma that would rapidly scavenge NO. Methods and Results Pulmonary vascular pressures and resistances to flow were measured in anesthetized newborn lambs. Plasma hemoglobin concentrations were then elevated, resulting in marked pulmonary hypertension. This effect was attenuated if infused hemoglobin was first oxidized to methemoglobin which does not scavenge NO. These results further implicate NO as a tonic pulmonary vasodilator. Next, while free hemoglobin continued to be infused, the lambs were given inhaled NO gas (20 ppm), inhaled sodium nitrite aerosol (0.87 M), or an intravascular nitrite infusion (3 mg·hr−1 bolus, 5 mg·kg−1·hr−1 infusion). Inhaled NO and inhaled nitrite aerosol both resulted in pulmonary vasodilation. Intravascular infusion of nitrite, however, did not. Increases in exhaled NO gas were observed while breathing the nitrite aerosol (~20 ppb NO) but not during intravascular infusion of nitrite. Conclusions We conclude that the pulmonary vasodilating effect of inhaled nitrite results from its conversion to NO in airway and parenchymal lung tissue and is not dependent on reactions with deoxyhemoglobin in the pulmonary circulation. Inhaled nitrite aerosol remains a promising candidate to reduce pulmonary hypertension in clinical application. PMID:21282501

Evaluating the use of the Cleo 90 infusion set for patients on a palliative care unit.

PubMed

Schneider, Michael; Hoffmann, Martin; Lorenzl, Stefan

2009-08-01

Although the use of subcutaneous infusion is common in palliative care, problems can occur. Normally, butterfly needles are used; however, there are occasional issues with patients being able to walk around or with restless patients who suffer from delirium. In these cases, needles often dislocate; therefore, a small observational study was undertaken to evaluate the use of the Cleo 90 infusion set. The use of this needle system has been well established in diabetic patients who require continuous subcutaneous infusion of insulin, but has never been tested in a wider range of patients with other medications. In this 6-month study, 45 patients were identified for subcutaneous infusion and a total of 112 needles were used for this study, since we initially changed each site after 2 days to control the local site for adverse reactions. We have not observed any complications with drug combinations delivered via the attached tube and the needle, and have used up to five different drugs mixed together in a single syringe. Needles could be used for a mean time of 5 +/- 2 days (range 2-12 days). Local site reactions have been observed only with sodium chloride infusions, which were not delivered via a pump system. Reddening and induration of the skin occurred, but they were reversible after removing the needle. As this was a small study in only one unit, without standardization the results can only be observational. However, it has shown, for the first time, that the Cleo 90 needle can be safe and comfortable.

The Effect of Systemic Steroid on Hearing Preservation After Cochlear Implantation via Round Window Approach: A Guinea Pig Model.

PubMed

Chang, Mun Young; Rah, Yoon Chan; Choi, Jun Jae; Woo, Shin Wook; Hwang, Yu-Jung; Eastwood, Hayden; O'Leary, Stephen J; Lee, Jun Ho

2017-08-01

When administered perioperatively, systemic dexamethasone will reduce the hearing loss associated with cochlear implantation (CI) performed via the round window approach. The benefits of electroacoustic stimulation have led to interest in pharmacological interventions to preserve hearing after CI. Thirty guinea pigs were randomly divided into three experimental groups: a control group; a 3-day infusion group; and a 7-day infusion group. Dexamethasone was delivered via a mini-osmotic pump for either 3 or 7 days after CI via the round window. Pure tone-evoked auditory brainstem response (ABR) thresholds were monitored for a period of 12 weeks after CI. The cochleae were then collected for histology. At 4 and 12 weeks after CI, ABR threshold shifts were significantly reduced in both 7-day and 3-day infusion groups compared with the control group. Furthermore, the 7-day infusion group has significantly reduced ABR threshold shifts compared with the 3-day infusion group. The total tissue response, including fibrosis and ossification, was significantly reduced in the 7-day infusion group compared with the control group. On multiple regression the extent of fibrosis predicted hearing loss across most frequencies, while hair cell counts predicted ABR thresholds at 32 kHz. Hearing protection after systemic administration of steroids is more effective when continued for at least a week after CI. Similarly, this treatment approach was more effective in reducing the fibrosis that encapsulates the CI electrode. Reduced fibrosis seemed to be the most likely explanation for the hearing protection.

[Palliative sedation].

PubMed

Verhagen, E H; Hesselmann, G M; Besse, T C; de Graeff, A

2005-02-26

Palliative sedation is the intentional lowering of the level of consciousness ofa patient in the last phase of life by means of the administration of sedatives. The objective of palliative sedation is to relieve severe physical or psychological suffering that is otherwise untreatable. Sedation is used in 12% of all patients dying in the Netherlands. Refractory delirium, dyspnoea or pain are the most common indications. If deep palliative sedation is used, the estimated life expectancy should be a few days to at most one week. Midazolam is used most often for continuous sedation, usually by subcutaneous infusion; if the response is insufficient, a combination of midazolam with levomepromazine or phenobarbital or monotreatment with propofol may be used. If continuous infusion is not desired or feasible, intermittent administration of midazolam, diazepam, lorazepam or chlorpromazine may be considered. Provided that it is used under the right circumstances, palliative sedation does not shorten life.

IL15 Infusion of Cancer Patients Expands the Subpopulation of Cytotoxic CD56bright NK Cells and Increases NK-Cell Cytokine Release Capabilities.

PubMed

Dubois, Sigrid; Conlon, Kevin C; Müller, Jürgen R; Hsu-Albert, Jennifer; Beltran, Nancy; Bryant, Bonita R; Waldmann, Thomas A

2017-10-01

The cytokine IL15 is required for survival and activation of natural killer (NK) cells as well as expansion of NK-cell populations. Here, we compare the effects of continuous IL15 infusions on NK-cell subpopulations in cancer patients. Infusions affected the CD56 bright NK-cell subpopulation in that the expansion rates exceeded those of CD56 dim NK-cell populations with a 350-fold increase in their total cell numbers compared with 20-fold expansion for the CD56 dim subset. CD56 bright NK cells responded with increased cytokine release to various stimuli, as expected given their immunoregulatory functions. Moreover, CD56 bright NK cells gained the ability to kill various target cells at levels that are typical for CD56 dim NK cells. Some increased cytotoxic activities were also observed for CD56 dim NK cells. IL15 infusions induced expression changes on the surface of both NK-cell subsets, resulting in a previously undescribed and similar phenotype. These data suggest that IL15 infusions expand and arm CD56 bright NK cells that alone or in combination with tumor-targeting antibodies may be useful in the treatment of cancer. Cancer Immunol Res; 5(10); 929-38. ©2017 AACR . ©2017 American Association for Cancer Research.

Effect of bile salt binding or protease inactivation on plasma cholecystokinin and gallbladder responses to bombesin.

PubMed

Thimister, P W; Hopman, W P; Sloots, C E; Rosenbusch, G; Tangerman, A; Willems, H L; Lamers, C B; Jansen, J B

1994-12-01

Bombesin-stimulated plasma cholecystokinin levels decrease after an initial increase despite continuous infusion of bombesin. The aim of this study was to determine if a feedback mechanism, mediated by bile salts or proteolytic enzymes, is responsible for this decline. Bombesin (1.0 ng.kg-1.min-1) was infused into volunteers for 180 minutes on separate occasions. Cholestyramine, colestipol, camostate, or saline were perfused intraduodenally during the second hour of the tests. Cholestyramine was also administered without infusion of bombesin. Colestipol and cholestyramine, dependent on their bile salt-binding capacity, markedly enhanced (P < 0.05) bombesin-stimulated plasma cholecystokinin from 2.1 +/- 0.5 pmol/L to 6.4 +/- 2.2 pmol/L and 12.1 +/- 3.3 pmol/L (P < 0.05 vs. colestipol), respectively, and further decreased gallbladder volume (P < 0.05) from 9.4 +/- 1.6 mL to 2.0 +/- 0.4 mL and 2.2 +/- 0.5 mL, respectively. The protease inhibitor camostate had no effect. Bile salt precipitation also enhanced plasma pancreatic polypeptide responses (P < 0.01) but did not alter gastrin responses. Plasma cholecystokinin responses to cholestyramine without bombesin infusion varied considerably, but increments were highly correlated to decreases in gallbladder volume (r = 0.91; P < 0.005). Bile salt sequestration but not protease inactivation enhances plasma cholecystokinin and gallbladder responses to bombesin infusion in humans.

Impaired Upper Esophageal Sphincter Reflexes in Patients with Supra-Esophageal Reflux Disease

PubMed Central

Babaei, Arash; Venu, Mukund; Naini, Sohrab Rahimi; Gonzaga, Jason; Lang, Ivan; Massey, Benson; Jadcherla, Sudarshan; Shaker, Reza

2015-01-01

Background & Aims Normal responses of the upper esophageal sphincter (UES) and esophageal body to liquid reflux events prevent esophagopharyngeal reflux and its complications, but abnormal responses have not been characterized. We investigated whether patients with supra-esophageal reflux disease (SERD) have impaired UES and esophageal body responses to simulated reflux events. Methods We performed a prospective study of 25 patients with SERD (19–82 y old, 13 female) and complaints of regurgitation and supra-esophageal manifestations of reflux. We also included 10 patients with gastroesophageal reflux disease (GERD; 32–60 y old, 7 female) without troublesome regurgitation and supra-esophageal symptoms and 24 healthy asymptomatic individuals (controls; 19–49 y old, 13 female). UES and esophageal body pressure responses, along with luminal distribution of infusate during esophageal rapid and slow infusion of air or liquid, were monitored by concurrent high-resolution manometry and intraluminal impedance. Results A significantly smaller proportion of patients with SERD had UES contractile reflexes in response to slow esophageal infusion of acid than controls or patients with GERD. Only patients with SERD had abnormal UES relaxation responses to rapid distension with saline. Diminished esophageal peristaltic contractions resulted in esophageal stasis in patients with GERD or SERD. Conclusions Patients with SERD and complaints of regurgitation have impaired UES and esophageal responses to simulated liquid reflux events. These patterns could predispose them to esophagopharyngeal reflux. PMID:26188682

Investigations on the effect of forage source, grinding, and urea supplementation on ruminal fermentation and microbial protein flow in a semi-continuous rumen simulation system.

PubMed

Hildebrand, Bastian; Boguhn, Jeannette; Rodehutscord, Markus

2011-10-01

The objective of the present study was to compare the effect of maize silage and grass silage on microbial fermentation and protein flow in a semi-continuous rumen simulation system (Rusitec) when milling screen size (MSS) during grinding was varied. Oven-dried silages were milled through screens of 1, 4 or 9 mm pore size and incubated for 48 h in a Rusitec system. Furthermore, the effect of N supplementation to maize silage (MSS: 4 mm) was investigated and single dose vs. continuous infusion of urea-N were compared. Degradation of organic matter (OM), crude protein (CP), fibre fractions and non-structural carbohydrates (NSC) as well as short-chain fatty acid production differed significantly between forage sources. Urea-N supplementation improved the degradation of NSC, but not that of fibre fractions in maize silage. The way of urea supply had only marginal effects on fermentation characteristics. An increase in MSS, and consequently in mean feed particle size, led to an improvement in the degradation of OM, CP and NSC, but efficiency of microbial net protein synthesis (EMPS; mg microbial N flow/g degraded OM) and the microbial amino acid profile were less affected. EMPS was higher in grass silage than in maize silage and was improved by urea-N supplementation in maize silage. This study indicates that fermentation of NSC as well as EMPS during incubation of maize silage was limited by availability of NH3-N. Furthermore, an increase in MSS above 1 mm seems to improve fermentation of silages in the Rusitec system.

Reducing the radiation dose from inhaled americium-241 using continuously administered DTPA therapy.

PubMed

Guilmette, R A; Muggenburg, B A

1988-02-01

Accelerating the removal of a radionuclide from the body of a contaminated individual is the only available approach to decreasing the radiation dose from such exposures. In this study, continuous infusion of a chelating agent, DTPA, was given to dogs that had inhaled a moderately soluble aerosol, 241 AmO2, not only to accelerate clearance of the radionuclide from the lung but also to prevent its deposition in liver and bone. Treatment was begun with an intravenous injection of CaDTPA 1 h after exposure, and was continued for 64 days after exposure by implanting subcutaneously osmotic pumps containing ZnDTPA at 1 day after exposure. The results showed that the infusion therapy was effective in blocking the translocation of 99.5 per cent of the 241Am that would have been deposited in liver, and 98.3 per cent of the 241Am that would have been deposited in bone. This result was significantly better than the result achieved using repeated intravenous injections of DTPA, the method of treatment in current use for actinide contamination cases.

High-dose phenobarbital with intermittent short-acting barbiturates for acute encephalitis with refractory, repetitive partial seizures.

PubMed

Uchida, Takashi; Takayanagi, Masaru; Kitamura, Taro; Nishio, Toshiyuki; Numata, Yurika; Endo, Wakaba; Haginoya, Kazuhiro; Ohura, Toshihiro

2016-08-01

Acute encephalitis with refractory, repetitive partial seizures (AERRPS) is characterized by repetitive seizures during the acute and chronic phases and has a poor neurological outcome. Burst-suppression coma via continuous i.v. infusion of a short-acting barbiturate is used to terminate refractory seizures, but the severe side-effects of short-acting barbiturates are problematic. We report on a 9-year-old boy with AERRPS who was effectively treated with very-high-dose phenobarbital (VHDPB) combined with intermittent short-acting barbiturates. VHDPB side-effects were mild, especially compared with those associated with continuous i.v. infusion of short-acting barbiturates (dosage, 40-75 mg/kg/day; maximum blood level, 290 μg/mL). Using VHDPB as the main treatment, short-acting barbiturates were used intermittently and in small amounts. This is the first report to show that VHDPB, combined with intermittent short-acting barbiturates, can effectively treat AERRPS. After treatment, convulsions were suppressed and daily life continued, but intellectual impairment and high-level dysfunction remained. © 2016 Japan Pediatric Society.

Half-molar sodium lactate infusion improves cardiac performance in acute heart failure: a pilot randomised controlled clinical trial.

PubMed

Nalos, Marek; Leverve, Xavier; Huang, Stephen; Weisbrodt, Leonie; Parkin, Ray; Seppelt, Ian; Ting, Iris; Mclean, Anthony

2014-03-25

Acute heart failure (AHF) is characterized by inadequate cardiac output (CO), congestive symptoms, poor peripheral perfusion and end-organ dysfunction. Treatment often includes a combination of diuretics, oxygen, positive pressure ventilation, inotropes and vasodilators or vasopressors. Lactate is a marker of illness severity but is also an important metabolic substrate for the myocardium at rest and during stress. We tested the effects of half-molar sodium lactate infusion on cardiac performance in AHF. We conducted a prospective, randomised, controlled, open-label, pilot clinical trial in 40 patients fulfilling two of the following three criteria for AHF: (1) left ventricular ejection fraction <40%, (2) acute pulmonary oedema or respiratory failure of predominantly cardiac origin requiring mechanical ventilation and (3) currently receiving vasopressor and/or inotropic support. Patients in the intervention group received a 3 ml/kg bolus of half-molar sodium lactate over the course of 15 minutes followed by 1 ml/kg/h continuous infusion for 24 hours. The control group received only a 3 ml/kg bolus of Hartmann's solution without continuous infusion. The primary outcome was CO assessed by transthoracic echocardiography 24 hours after randomisation. Secondary outcomes included a measure of right ventricular systolic function (tricuspid annular plane systolic excursion (TAPSE)), acid-base balance, electrolyte and organ function parameters, along with length of stay and mortality. The infusion of half-molar sodium lactate increased (mean ± SD) CO from 4.05 ± 1.37 L/min to 5.49 ± 1.9 L/min (P < 0.01) and TAPSE from 14.7 ± 5.5 mm to 18.3 ± 7 mm (P = 0.02). Plasma sodium and pH increased (136 ± 4 to 146 ± 6 and 7.40 ± 0.06 to 7.53 ± 0.03, respectively; both P < 0.01), but potassium, chloride and phosphate levels decreased. There were no significant differences in the need for vasoactive therapy, respiratory support, renal or liver function tests, duration of ICU and hospital stay or 28- and 90-day mortality. Infusion of half-molar sodium lactate improved cardiac performance and led to metabolic alkalosis in AHF patients without any detrimental effects on organ function. Clinicaltrials.gov NCT01981655. Registered 13 August 2013.

Insulin production rate in normal man as an estimate for calibration of continuous intravenous insulin infusion in insulin-dependent diabetic patients.

PubMed

Waldhäusl, W K; Bratusch-Marrain, P R; Francesconi, M; Nowotny, P; Kiss, A

1982-01-01

This study examines the feasibility of deriving the 24-h insulin requirement of insulin-dependent diabetic patients who were devoid of any endogenous insulin release (IDD) from the insulin-production rate (IPR) of healthy man (basal, 17 mU/min; stimulated 1.35 U/12.5 g glucose). To this end, continuous intravenous insulin infusion (CIVII) was initiated at a precalculated rate of 41.2 +/- 4.6 (SD) U/24 h in IDD (N - 12). Blood glucose profiles were compared with those obtained during intermittent subcutaneous (s.c.) insulin therapy (IIT) and those of healthy controls (N = 7). Regular insulin (Hoechst CS) was infused with an adapted Mill Hill Infuser at a basal infusion rate of 1.6 U/h (6:00 a.m. to 8:00 p.m.), and of 0.8 U/h from 8:00 p.m. to 6:00 a.m. Preprandial insulin (3.2-6.4 U) was added for breakfast, lunch, and dinner. Daily individual food intake totaled 7688 +/- 784 kJ (1836 +/- 187 kcal)/24 h including 184 +/- 37 g of glucose. Proper control of blood glucose (BG) (mean BG 105 +/- 10 mg/dl; mean amplitude of glycemic excursions 54 +/- 18 mg/dl; and 1 h postprandial BG levels not exceeding 160 mg/dl) and of plasma concentrations of beta-hydroxybutyrate and lactate was maintained by 41.4 +/- 4.4 U insulin/24 h. Although BG values only approximated the upper normal range as seen in healthy controls, they were well within the range reported by others during CIVII. Therefore, we conclude that in adult IDD completely devoid of endogenous insulin (1) the IPR of normal man can be used during CIVII as an estimate for the patient's minimal insulin requirement per 24 h, and (2) this approach allows for a blood glucose profile close to the upper range of a normal control group. Thus, deriving a patient's daily insulin dose from the insulin production rate of healthy man may add an additional experimental protocol which aids in making general calculations of a necessary insulin dose instead of using trial and error or a closed-loop insulin infusion system.

Effects of acetic acid or sodium acetate infused into the rumen or abomasum on feeding behavior and metabolic response of cows in the postpartum period.

PubMed

Gualdrón-Duarte, Laura B; Allen, Michael S

2018-03-01

Effects of continuous isomolar infusions of acetic acid (AcA) or sodium acetate (NAc) infused into the rumen (RU) or into the abomasum (AB) on feeding behavior, dry matter intake (DMI), and metabolic response of cows in the early postpartum period were evaluated. Six rumen-cannulated multiparous Holstein cows (11.8 ± 3.9 d in milk; mean ± SD) were utilized in a 6 × 6 Latin square design experiment balanced for carryover effects with a 2 × 3 factorial arrangement of treatments. Treatments were AcA and NAc, with sodium chloride (CON) as a control, infused at a rate of ˜0.75 mol/h (0.5 L/h) into the RU or AB for the first 8 h following feeding, with a rest day between infusion days. Treatment sequences were assigned randomly to cows. Feeding behavior was recorded by a computerized data acquisition system and blood was sampled at 0, 4, and 8 h relative to the start of infusion. We hypothesized that AcA is more hypophagic than NAc, and that infusion into the AB is more hypophagic than infusion into the RU. Dry matter intakes (DMI) for the CON treatments were similar at 6.2 kg/8 h for RU and 6.1 kg/8 h for AB, and the AcA and NAc treatments interacted with site of infusion to affect DMI. The NAc-RU treatment did not reduce DMI (7.0 kg/8 h), whereas AcA-RU (2.6 kg/8 h), AcA-AB (3.7 kg/8 h), and NAc-AB (4.0 kg/8 h) decreased DMI compared with CON. Following infusions of AcA compared with NAc, there was a residual effect on DMI for the remainder of the day, but treatments did not affect DMI during the rest day. Treatments increased plasma acetate and β-hydroxybutyrate concentrations over time (interaction) and decreased plasma insulin concentration compared with CON. Plasma glucose concentration decreased over time after AcA-AB infusion compared with other treatments and CON. Plasma nonesterified fatty acid concentration increased over time for AcA compared with NAc and CON, suggesting an increase in lipolysis to compensate the decrease in DMI. In contrast to the other treatments, NAc-RU did not decrease DMI compared with control but we cannot determine the reason for this from the data available from the current study. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Globe stability during simulated vitrectomy with valved and non-valved trocar cannulas

PubMed Central

Abulon, Dina Joy; Charles, Martin; Charles, Daniel E

2015-01-01

Purpose To compare the effects of valved and non-valved cannulas on intraocular pressure (IOP), fluid leakage, and vitreous incarceration during simulated vitrectomy. Methods Three-port pars plana incisions were generated in six rubber eyes using 23-, 25-, and 27-gauge valved and non-valved trocar cannulas. The models were filled with air and IOP was measured. Similar procedures were followed for 36 acrylic eyes filled with saline solution. Vitreous incarceration was analyzed in eleven rabbit and twelve porcine cadaver eyes. Results In the air-filled model, IOP loss was 89%–94% when two non-valved cannulas were unoccupied versus 1%–5% when two valved cannulas were unoccupied. In the fluid-filled model, with non-valved cannulas, IOP dropped while fluid leaked from the open ports. With two open ports, the IOP dropped to 20%–30% of set infusion pressure, regardless of infusion pressure and IOP compensation. The IOP was maintained in valved cannulas when one or two ports were left open, regardless of IOP compensation settings. There was no or minimal fluid leakage through open ports at any infusion pressure. Direct microscopic analysis of rabbit eyes showed that vitreous incarceration was significantly greater with 23-gauge non-valved than valved cannulas (P<0.005), and endoscopy of porcine eyes showed that vitreous incarceration was significantly greater with 23-gauge (P<0.05) and 27-gauge (P<0.05) non-valved cannulas. External observation of rabbit eyes showed vitreous prolapse through non-valved, but not valved, cannulas. Conclusion Valved cannulas surpassed non-valved cannulas in maintaining IOP, preventing fluid leakage, and reducing vitreous incarceration during simulated vitrectomy. PMID:26445520

Effect of different surgical procedures on the accuracy of prediction of the plasma concentration of fentanyl: comparison between mastectomy and laparoscopic prostatectomy.

PubMed

Fujita, Yoshihito; Yoshizawa, Saya; Hoshika, Maiko; Inoue, Koichi; Matsushita, Shoko; Oka, Hisao; Sobue, Kazuya

2017-01-01

The accuracy of simulation-predicted fentanyl concentration in different types of surgical procedure is not fully understood. We wished to estimate the effect of different types of surgical procedure on the accuracy of such simulations. Fifty patients who had undergone elective mastectomy or laparoscopic prostatectomy (American Society of Anesthesiologists physical status = I-II) were enrolled. Anesthesia was maintained throughout surgery with sevoflurane and a bolus infusion of fentanyl. A maintenance infusion was administered with 8 mL/kg/h Ringer's acetate solution from the start of anesthesia to completion of blood sampling. An infusion to compensate for blood loss was administered (one to two volumes of hydroxyethyl starch). A blood sample was drawn every 30 min during anesthesia.We measured the plasma concentration of fentanyl in 358 samples from 50 patients. The plasma concentration of fentanyl was correlated significantly with the simulated predicted fentanyl concentration ( r  = 0.734, P  < 0.01) but 36.0% of all samples had a difference greater than ±0.5 ng/mL. Approximately 0.3 ng/mL of a fixed bias was shown throughout mastectomy. During laparoscopic prostatectomy, the fixed bias gradually became negative from ≈0.3 to -0.3 ng/mL as the sampling stage proceeded. The predicted concentration of fentanyl was significantly correlated with the plasma concentration of fentanyl ( r  = 0.734). However, there were different patterns of a fixed bias between mastectomy and laparoscopic prostatectomy groups. We should pay attention to this tendency among different surgical procedures. UMIN000005110.

Comparison between a disposable and an electronic PCA device for labor epidural analgesia.

PubMed

Sumikura, Hiroyuki; van de Velde, Marc; Tateda, Takeshi

2004-01-01

The aims of the present study were (1) to investigate if a disposable patient-controlled analgesia (PCA) device can be used for labor analgesia and (2) to evaluate the device by midwives and parturients. Forty healthy parturients were divided into two groups and received combined spinal epidural analgesia for labor pain relief. Following intrathecal administration of 3 mg ropivacaine and 1.5 microg sufentanil, either a disposable PCA device (Coopdech Syrinjector; Daiken Medical, Osaka, Japan) or an electronic PCA device (IVAC PCAM PCA Syringe Pump; Alaris, Basingstoke, UK) was connected to the epidural catheter, and 0.15% ropivacaine with sufentanil 0.75 microg/ml was used for continuous infusion and PCA. For an electronic PCA device, continuous infusion rate, bolus dose, lockout time, and hourly limit were set at 4 ml/h, 3 ml, 15 min, and 16 ml, respectively. For a disposable PCA device, continuous infusion rate, bolus dose, and an hourly limit were set at 4 ml/h, 3 ml, and 16 ml, respectively, but lockout function was not available. No differences were observed between the groups concerning demographic data, obstetric data, and outcome of labor. Anesthetic requirements (disposable, 9.7 +/- 4.7 ml/h; electronic, 8.2 +/- 4.0 ml/h) and VAS score during the delivery (disposable, 26 +/- 25; electronic, 21 +/- 22) were similar between the groups. Midwives praised the disposable PCA device as well as the electronic one. The present results imply that the disposable PCA device can be an alternative to the electronic PCA device for labor analgesia.

[Vasopressin intravenous infusion causes dose dependent adverse cardiovascular effects in anesthetized dogs.

PubMed

Martins, Luiz Cláudio; Sabha, Maricene; Paganelli, Maria Ondina; Coelho, Otávio Rizzi; Ferreira-Melo, Silvia Elaine; Moreira, Marcos Mello; Cavalho, Adriana Camargo de; Araujo, Sebastião; Moreno Junior, Heitor

2010-01-15

BACKGROUND: Arginine vasopressin (AVP) has been broadly used in the management of vasodilatory shock. However, there are many concerns regarding its clinical use, especially in high doses, as it can be associated with adverse cardiovascular events. OBJECTIVE: To investigate the cardiovascular effects of AVP in continuous IV infusion on hemodynamic parameters in dogs. METHODS: Sixteen healthy mongrel dogs, anesthetized with pentobarbital were intravascularly catheterized, and randomly assigned to: control (saline-placebo; n=8) and AVP (n=8) groups. The study group was infused with AVP for three consecutive 10-minute periods at logarithmically increasing doses (0.01; 0.1 and 1.0U/kg/min), at them 20-min intervals. Heart rate (HR) and intravascular pressures were continuously recorded. Cardiac output was measured by the thermodilution method. RESULTS: No significant hemodynamic effects were observed during 0.01U/kg/min of AVP infusion, but at higher doses (0.1 and 1.0U/kg/min) a progressive increase in mean arterial pressure (MAP) and systemic vascular resistance index (SVRI) were observed, with a significant decrease in HR and the cardiac index (CI). A significant increase in the pulmonary vascular resistance index (PVRI) was also observed with the 1.0U/kg/min dose, mainly due to the decrease in the CI. CONCLUSION: AVP, when administered at doses between 0.1 and 1.0U/kg/min, induced significant increases in MAP and SVRI, with negative inotropic and chronotropic effects in healthy animals. Although these doses are ten to thousand times greater than those routinely used for the management of vasodilatory shock, our data confirm that AVP might be used carefully and under strict hemodynamic monitoring in clinical practice, especially if doses higher than 0.01 U/kg/min are needed. Martins, LC et al.

Lumbar paravertebral blockade as intractable pain management method in palliative care

PubMed Central

Zaporowska-Stachowiak, Iwona; Kotlinska-Lemieszek, Aleksandra; Kowalski, Grzegorz; Kosicka, Katarzyna; Hoffmann, Karolina; Główka, Franciszek; Łuczak, Jacek

2013-01-01

Optimal symptoms control in advanced cancer disease, with refractory to conventional pain treatment, needs an interventional procedure. This paper presents coadministration of local anesthetic (LA) via paravertebral blockade (PVB) as the alternative to an unsuccessful subcutaneous fentanyl pain control in a 71-year old cancer patient with pathological fracture of femoral neck, bone metastases, and contraindications to morphine. Bupivacaine in continuous infusion (0.25%, 5 mL · hour−1) or in boluses (10 mL of 0.125%–0.5% solution), used for lumbar PVB, resulted in pain relief, decreased demand for opioids, and led to better social interactions. The factors contributing to an increased risk of systemic toxicity from LA in the patient were: renal impairment; heart failure; hypoalbuminemia; hypocalcemia; and a complex therapy with possible drug-drug interactions. These factors were taken into consideration during treatment. Bupivacaine’s side effects were absent. Coadministered drugs could mask LA’s toxicity. Elevated plasma α1-acid glycoprotein levels were a protective factor. To evaluate the benefit-risk ratio of the PVB treatment in boluses and in constant infusion, bupivacaine serum levels were determined and the drug plasma half-lives were calculated. Bupivacaine’s elimination was slower when administered in constant infusion than in boluses (t½ = 7.80 hours versus 2.64 hours). Total drug serum concentrations remained within the safe ranges during the whole treatment course (22.9–927.4 ng mL−1). In the case presented, lumbar PVB with bupivacaine in boluses (≤ 137.5 mg · 24 hours−1) was an easy to perform, safe, effective method for pain control. Bupivacaine in continuous infusion (≤150 mg · 12 hours−1) had an acceptable risk-benefits ratio, but was ineffective. PMID:24043944

Lumbar paravertebral blockade as intractable pain management method in palliative care.

PubMed

Zaporowska-Stachowiak, Iwona; Kotlinska-Lemieszek, Aleksandra; Kowalski, Grzegorz; Kosicka, Katarzyna; Hoffmann, Karolina; Główka, Franciszek; Luczak, Jacek

2013-01-01

Optimal symptoms control in advanced cancer disease, with refractory to conventional pain treatment, needs an interventional procedure. This paper presents coadministration of local anesthetic (LA) via paravertebral blockade (PVB) as the alternative to an unsuccessful subcutaneous fentanyl pain control in a 71-year old cancer patient with pathological fracture of femoral neck, bone metastases, and contraindications to morphine. Bupivacaine in continuous infusion (0.25%, 5 mL · hour(-1)) or in boluses (10 mL of 0.125%-0.5% solution), used for lumbar PVB, resulted in pain relief, decreased demand for opioids, and led to better social interactions. The factors contributing to an increased risk of systemic toxicity from LA in the patient were: renal impairment; heart failure; hypoalbuminemia; hypocalcemia; and a complex therapy with possible drug-drug interactions. These factors were taken into consideration during treatment. Bupivacaine's side effects were absent. Coadministered drugs could mask LA's toxicity. Elevated plasma α1-acid glycoprotein levels were a protective factor. To evaluate the benefit-risk ratio of the PVB treatment in boluses and in constant infusion, bupivacaine serum levels were determined and the drug plasma half-lives were calculated. Bupivacaine's elimination was slower when administered in constant infusion than in boluses (t½ = 7.80 hours versus 2.64 hours). Total drug serum concentrations remained within the safe ranges during the whole treatment course (22.9-927.4 ng mL(-1)). In the case presented, lumbar PVB with bupivacaine in boluses (≤ 137.5 mg · 24 hours(-1)) was an easy to perform, safe, effective method for pain control. Bupivacaine in continuous infusion (≤150 mg · 12 hours(-1)) had an acceptable risk-benefits ratio, but was ineffective.

Effects of low-dose IV ketamine on peripheral and central pain from major limb injuries sustained in combat.

PubMed

Polomano, Rosemary C; Buckenmaier, Chester C; Kwon, Kyung H; Hanlon, Alexandra L; Rupprecht, Christine; Goldberg, Cynthia; Gallagher, Rollin M

2013-07-01

Examine response patterns to low-dose intravenous (IV) ketamine continuous infusions on multiple pain outcomes, and demonstrate effectiveness, safety, and tolerability of ketamine administration on general wards. Retrospective case series of consecutive patients given low-dose IV ketamine continuous infusions. Walter Reed Army Medical Center, Washington, DC. Nineteen eligible inpatients with neuropathic pain from major limb injuries sustained in combat with inadequate pain control from multimodal analgesia. A 3-day IV infusion of ketamine at doses ≤ 120 μg/kg/h. Daily present (PPI), average (API), and worst (WPI) pain intensity (0-10), global pain relief (GPR) (1 "no relief" to 5 "complete relief"), daily assessments of adverse events, and daily opioid requirements measured during therapy. A significant reduction in PPI (P < 0.001) and improvement in GPR (P = 0.031) was noted over time. Higher baseline WPI (≥ 7; N = 4) was associated with a significant decrease in WPI (P = 0.0388), but lower baseline WPI (N = 5) was not. Significant mean percent decreases in PPI with higher baseline PPI (N = 8; P = 0.0078) and WPI with no phantom limb pain (PLP) (N = 10; P = 0.0436) were observed. Mean percent increase in overall GPR was better for those reporting GPR scores ≤ 3 (N = 13) in the first 24 hours of therapy (P = 0.0153). While not significant, mean opioid requirement (IV morphine equivalents) decreased from 129.9 mgs ± 137.3 on day 1 to 112.14 ± 86.3 24 hours after therapy. Low-dose ketamine infusions for complex combat injury pain were safe and effective, and demonstrated response patterns over time and by baseline pain score stratification and presence or absence of PLP. Wiley Periodicals, Inc.

Continuous Subcutaneous Insulin Infusion versus Multiple Daily Injections of Insulin for the Management of Type 1 Diabetes Mellitus in Pregnancy: Association with Neonatal Chemical Hypoglycemia.

PubMed

Sargent, James A; Roeder, Hilary A; Ward, Kristy K; Moore, Thomas R; Ramos, Gladys A

2015-12-01

We hypothesized that patients with type 1 diabetes mellitus (T1DM) who were managed during their pregnancy with a continuous subcutaneous insulin infusion (CSII) would have a lower incidence of neonatal hypoglycemia (NH) than patients managed with multiple daily injections (MDI) of insulin. This was a retrospective cohort of 95 women with T1DM who delivered singleton, term neonates between 2007 and 2014. The primary outcome was incidence of NH (capillary plasma glucose ≤ 45 mg/dL) in the first 24 hours after birth. The incidence of NH was 66.0% (62/95). The NH rate was significantly higher in women managed with CSII versus MDI (62 vs. 38%, p = 0.024). Neonates with NH had a higher birth weight (3,867 ± 658 vs. 3,414 ± 619 g, p = 0.002). When analyzing intrapartum glucose management, mothers of neonates with NH had significantly less time managed on an insulin infusion (median interquartile range 7 [3.5-30.5] vs. 17.5 [2.0-17.5] hours, p = 0.014). In multivariable analysis, only maternal body mass index (BMI) (p = 0.035) and time on an insulin infusion (p = 0.043) were significantly associated with NH. In our population of patients with T1DM, CSII was more prevalent in the NH group; however, when controlling for other factors, intrapartum glucose management and early maternal BMI were the only variables associated with NH. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The chronic infusion of hexamethonium and phenylephrine to effectively clamp sympathetic vasomotor tone. A novel approach.

PubMed

Collister, J P; Osborn, J W

1999-11-01

There are several ways to assess the sympathetic nervous system (i.e. , nerve recording, sympathectomy, etc.), each of which has its own limitations. The present study was conducted to establish a standard, testable chronic ganglionic blockade protocol with a fixed level of adrenergic vasomotor tone. Rats were instrumented with radio telemetry pressure transducers and venous catheters for continuous measurement of arterial pressure and infusion of pharmacologic agents, respectively. After 3 days of control measurements, rats were infused for 9 days with a continuous dose of the ganglionic blocking agent, hexamethonium and the alpha-adrenergic agonist, phenylephrine. In this way, sympathetic tone was effectively "clamped," which maintained a normal level of arterial pressure. Control pressure between hexamethonium + phenylephrine (HEX + PE) treated rats (101+/-2 mm Hg) and saline (VEHICLE) treated rats (101+/-2 mmHg) was not different. By day 9 of the infusion, there was no difference in arterial pressure between groups (VEHICLE: 101+/-3 mm Hg, HEX + PE: 103+/-3 mm Hg) or from the control period, although heart rate was significantly less in HEX + PE rats (VEHICLE: 406+/-9 beats/min vs. HEX + PE: 343+/-6 beats/min). The effectiveness of this technique was validated by measuring cardiac baroreceptor reflex sensitivity, as well as the pressor response to the direct ganglionic stimulating agent, 1, 1-dimethyl-4-phenylpiperazinium iodide (DMPP). Compared to VEHICLE rats, HEX + PE rats showed no tachycardic response to depressor stimuli and an absence of a pressor response to DMPP. We conclude that this protocol is a useful technique to chronically, yet reversibly, block the sympathetic nervous system in experimental settings.

Comparison of intracoronary versus intravenous administration of adenosine for measurement of coronary fractional flow reserve.

PubMed

Schlundt, Christian; Bietau, Christian; Klinghammer, Lutz; Wiedemann, Ricarda; Rittger, Harald; Ludwig, Josef; Achenbach, Stephan

2015-05-01

Measurement of fractional flow reserve (FFR) constitutes the current gold standard to evaluate the hemodynamic significance of coronary stenoses. Limited data validate the intracoronary application of adenosine against standard intravenous infusion. We systematically compared FFR measurements during intracoronary and intravenous application of adenosine about agreement and reproducibility. We included 114 patients with an intermediate degree of stenosis in coronary angiography. Two FFR measurements were performed during intracoronary bolus injection (40 μg for the right and 80 μg for the left coronary artery, FFRic), and 2 FFR measurements during continuous intravenous infusion of adenosine (140 μg/kg per minute, FFRiv). FFR value, the time to reach FFR and patient discomfort (on a subjective scale from 0 for no symptoms to 5 for maximal discomfort) were recorded for each measurement. Mean time to FFR was 100 ± 27 s for continuous intravenous infusion versus 23 ± 14 s for intracoronary bolus administration of adenosine (P < 0.001). Reported discomfort after intracoronary application was significantly lower compared with intravenous adenosine (subjective scale > 0 in 35.1% versus 87.7% of the patients; P < 0.001). Correlation between FFRiv and FFRic was extremely close (r = 0.99; P < 0.001) with no systematic bias in Bland-Altman analysis (bias 0.002 [confidence interval, -0.001 to 0.005]) and low intermethod variability (1.56%). Intramethod variability was not different between intravenous and intracoronary administration (1.47% versus 1.33%; P=0.5). Intracoronary bolus injection of adenosine (40 μg for the right and 80 μg for the left coronary artery) yields identical FFR results compared with intravenous infusion (140 μg/kg per minute), while requiring less time and offering superior patient comfort. © 2015 American Heart Association, Inc.

Bedside red cell volumetry by low-dose carboxyhaemoglobin dilution using expiratory gas analysis.

PubMed

Sawano, M; Mato, T; Tsutsumi, H

2006-02-01

We developed a non-invasive, continuous, high-resolution method of measuring carboxyhaemoglobin fraction (COHb%) using expiratory gas analysis (EGA). We assessed whether application of EGA to carboxyhaemoglobin dilution provides red cell volume (RCV) measurement with accuracy equivalent to that of CO-haemoximetry, with a smaller infusion volume of carbon-monoxide-saturated autologous blood (COB). Method. We assessed the agreement between repeated COHb% measurements by EGA and simultaneous measurement by CO-haemoximetry, using Bland and Altman plot, in healthy subjects and patients with artificially controlled ventilation and no radiological evidence of pulmonary oedema or atelectasis. We assessed the agreement between RCV measurements by EGA with infusion of 20 ml of COB (RCVEGA) and RCV measurements by CO-haemoximetry with infusion of 100 ml of COB (RCVHEM), in healthy subjects. The 'limits of agreement' between COHb% measurement by EGA (1 min average) and CO-haemoximetry were -0.09 and 0.08% in healthy subjects, and -0.11 and 0.09% in patients. Given the resolution of CO-haemoximetry (0.1%), the accuracy of EGA was equivalent to or greater than that of CO-haemoximetry. The 'limits of agreement' between RCVEGA and RCVHEM were -0.14 and 0.15 litre. Given the average resolution of RCVHEM (0.14 litre), the accuracy of RCVEGA was equivalent to that of RCVHEM. EGA provided non-invasive, accurate, continuous, high-resolution COHb% measurements. Applying EGA to carboxyhaemoglobin dilution, we achieved RCV measurements with accuracy equivalent to that of CO-haemoximetry, with one-fifth of the COB infusion volume. However, clinical application of the method is limited to patients with no radiological evidence of pulmonary oedema or atelectasis.

The effect of on-demand vs deep neuromuscular relaxation on rating of surgical and anaesthesiologic conditions in patients undergoing thoracolaparoscopic esophagectomy (DEPTH trial): study protocol for a randomized controlled trial.

PubMed

Veelo, Denise P; Gisbertz, Suzanne S; Hannivoort, Rebekka A; van Dieren, Susan; Geerts, Bart F; van Berge Henegouwen, Mark I; Hollmann, Markus W

2015-08-05

Deep muscle relaxation has been shown to facilitate operating conditions during laparoscopic surgery. Minimally invasive esophageal surgery is a high-risk procedure in which the use of deep neuromuscular block (NMB) may improve conditions in the thoracic phase as well. Neuromuscular antagonists can be given on demand or by continuous infusion (deep NMB). However, the positioning of the patient often hampers train-of-four (TOF) monitoring. A continuous infusion thus may result in a deep NMB at the end of surgery. The use of neostigmine not only is insufficient for reversing deep NMB but also may be contraindicated for this procedure because of its cholinergic effects. Sugammadex is an effective alternative but is rather expensive. This study aims to evaluate the use of deep versus on-demand NMB on operating, anaesthesiologic conditions, and costs in patients undergoing a two- or three-phase thoracolaparoscopic esophageal resection. We will conduct a single-center randomized controlled double-blinded intervention study. Sixty-six patients undergoing a thoracolaparoscopic esophageal resection will be included. Patients will receive either continuous infusion of rocuronium 0.6 mg/kg per hour (group 1) or continuous infusion of NaCl 0.9 % 0.06 ml/kg per hour (group 2). In both groups, on-demand boluses of rocuronium can be given (open-label design). The primary aim of this study is to compare the surgical rating scale (SRS) during the abdominal phase. Main secondary aims are to evaluate SRS during the thoracic phase, to evaluate anesthesiologic conditions, and to compare costs (in euros) associated with use of rocuronium, sugammadex, and duration of surgery. This study is the first to evaluate the benefits of deep neuromuscular relaxation on surgical and anaesthesiologic conditions during thoracolaparoscopic esophageal surgery. This surgical procedure is unique because it consists of both an abdominal phase and a thoracic phase taking place in different order depending on the subtype of surgery (a two- or three-stage transthoracic esophagectomy). In addition, possible benefits associated with deep NMB, such as decrease in operating time, will be weighed against costs. European Clinical Trials Database (EudraCT) number: 2014-002147-18 (obtained 19 May 2014) ClinicalTrials.gov: NCT02320734 (obtained 18 Dec. 2014).

Drug Delivery: Enabling Technology for Drug Discovery and Development. iPRECIO® Micro Infusion Pump: Programmable, Refillable, and Implantable

PubMed Central

Tan, Tsung; Watts, Stephanie W.; Davis, Robert Patrick

2011-01-01

Successful drug delivery using implantable pumps may be found in over 12,500 published articles. Their versatility in delivering continuous infusion, intermittent or complex infusion protocols acutely or chronically has made them ubiquitous in drug discovery and basic research. The recent availability of iPRECIO®, a programmable, refillable, and implantable infusion pump has made it possible to carry out quantitative pharmacology (PKPD) in single animals. When combined with specialized catheters, specific administration sites have been selected. When combined with radiotelemetry, the physiologic gold standard, more sensitive and powerful means of detecting drug induced therapeutic, and/or adverse effects has been possible. Numerous application examples are cited from iPRECIO® use in Japan, United States, and Europe with iPRECIO® as an enabling drug delivery device where the refillable and programmability functionality were key benefits. The ability to start/stop drug delivery and to have control periods prior dosing made it possible to have equivalent effects at a much lower dose than previously studied. Five different iPRECIO® applications are described in detail with references to the original work where the implantable, refillable, and programmable benefits are demonstrated with their different end-points. PMID:21863140

A fuzzy logic controller for hormone administration using an implantable pump

NASA Technical Reports Server (NTRS)

Coles, L. Stephen; Wells, George H., Jr.

1994-01-01

This paper describes the requirements for a Fuzzy Logic Controller for the physiologic administration of hormones by means of a FDA-approved surgically implantable infusion pump. Results of a LabVIEW computer simulation for the administration of insulin for diabetic adult patients as well as human growth hormone for pediatric patients are presented. A VHS video tape of the simulation in action has been prepared and is available for viewing.

Temporary quadriplegia following continuous thoracic paravertebral block.

PubMed

Calenda, Emile; Baste, Jean Marc; Danielou, Eric; Michelin, Paul

2012-05-01

A case of temporary quadriplegia following a continuous thoracic paravertebral block in an adult patient scheduled for video-assisted thoracoscopy is presented. An 18-gauge Tuohy needle was inserted under direct vision by the surgeon but the tip of the catheter was not localized. Postoperatively, the patient developed temporary quadriplegia 90 minutes after the start of a continuous infusion of ropivacaine 0.2%. Imaging studies showed that the catheter was localized in the intrathecal space. Copyright © 2012 Elsevier Inc. All rights reserved.

[Methods for increasing the immunogenicity of vaccines].

PubMed

Kündig, T M

2000-09-14

In the past years, enormous efforts have been undertaken to develop vaccine strategies against cancer. The aim is to have the immune system generate what are called killer cells that can specifically recognize the tumor. The surface of tumor cells contains MHC/HLA antigens which present short-chain peptides of tumor specific antigens. A large number of these oligopeptide antigens have been characterized in recent years. They are now available for use as tumor-specific vaccines. The problem is, however, that the immune response of producing T killer cells is very inefficient when these oligopeptide antigens are injected. As the physiological function of these killer cells virus-infected cells, a process associated with substantial tissue damage, the immune system has learned to use these killer cells with reticence over the course of evolution, in other words, when the life of the host is threatened. This does not happen until pathogens start to spread via lymphogenous or hematogenous pathways. And then it takes a certain amount of time after the invader is present for replication to take place. Since the oligopeptide antigens used as vaccines have a very short half-life in the tissue, not enough of them get to the lymph nodes and stay there for enough time to efficiently induce an immune response. Using a mouse model, we were able to show that the efficiency of the vaccine can be increased a million-fold by directly injecting the vaccine into a lymph node or the spleen which imitates lymphogenous or hematogenous spread. The efficiency of the "inactivated vaccine" can be enhanced even more by continuous administration of the vaccine over several days, simulating an especially dangerous virus replication. The evidence gathered in this mouse model was transferred to a clinical trial. The melanoma-specific inactivated vaccine is infused directly into a lymph node of tumor patients. The infusion is continued for several days. Booster vaccines are given every two weeks.

Colonic motor and vascular responses to pelvic nerve stimulation and their relation to local peptide release in the cat.

PubMed Central

Andersson, P O; Bloom, S R; Järhult, J

1983-01-01

1. The effects of stimulation of the pelvic nerves in atropinized cats at continuous, low frequencies from 1 to 16 Hz (continuous stimulation) were compared with those of stimulation at higher frequencies (10-160 Hz) delivered in 1 s bursts at 10 s intervals (stimulation in bursts), the latter simulating a commonly observed discharge pattern in vivo. Both types of stimulation evoked a transient vasodilatation. Stimulation in bursts at 20 and 40 Hz evoked more pronounced vasodilatations than continuous stimulation delivering exactly the same number of impulses over the whole period of excitation. 2. Stimulation of the pelvic nerves in bursts failed to elicit an effective contraction of the colon at any frequency tested, whereas continuous stimulation invariably evoked a contraction. 3. There was a clear-cut increase in the output of vasoactive intestinal polypeptide during both continuous and intermittent stimulation of the pelvic nerves. Stimulation in bursts caused a small but significant increase in the output of somatostatin but there was no change in the output of substance P in response to either type of pelvic nerve stimulation. 4. The colonic muscular contraction in response to continuous stimulation of the pelvic nerves was not affected by somatostatin when infused intra-arterially at the large dose of 1.0 microgram/min. 5. It is concluded that the colonic responses of atropinized cats to pelvic nerve stimulation can be substantially altered merely by changing the pattern of stimulation. Thus, whereas continuous stimulation produces both muscular contraction and vasodilatation, stimulation in bursts favours vasodilatation but is ineffective in eliciting colonic contraction. PMID:6191025

Evaluation of propylene glycol and glycerol infusions as treatments for ketosis in dairy cows.

PubMed

Piantoni, P; Allen, M S

2015-08-01

To evaluate propylene glycol (PG) and glycerol (G) as potential treatments for ketosis, we conducted 2 experiments lasting 4 d each in which cows received one bolus infusion per day. Blood was collected before infusion, over 240min postinfusion, as well as 24 h postinfusion. Experiment 1 used 6 ruminally cannulated cows (26±7 d in milk) randomly assigned to 300-mL infusions of PG or G (both ≥99.5% pure) in a crossover design experiment with 2 periods. Within each period, cows were assigned randomly to infusion site sequence: abomasum (A)-cranial reticulorumen (R) or the reverse, R-A. Glucose precursors were infused into the R to simulate drenching and the A to prevent metabolism by ruminal microbes. Glycerol infused in the A increased plasma glucose concentration the most (15.8mg/dL), followed by PG infused in the R (12.6mg/dL), PG infused in the A (9.11mg/dL), and G infused in the R (7.3mg/dL). Infusion of PG into the R increased plasma insulin and insulin area under the curve (AUC) the most compared with all other treatments (7.88 vs. 2.13μIU/mL and 321 vs. 31.9min×μIU/mL, respectively). Overall, PG decreased plasma BHBA concentration after infusion (-6.46 vs. -4.55mg/dL) and increased BHBA AUC (-1,055 vs. -558min ×mg/dL) compared with G. Plasma NEFA responses were not different among treatments. Experiment 2 used 8 ruminally cannulated cows (22±5 d in milk) randomly assigned to treatment sequence in a Latin square design experiment balanced for carryover effects. Treatments were 300mL of PG, 300mL of G, 600mL of G (2G), and 300mL of PG + 300mL of G (GPG), all infused into the R. Treatment contrasts compared PG with each treatment containing glycerol (G, 2G, and GPG). Propylene glycol increased plasma glucose (14.0 vs. 5.35mg/dL) and insulin (7.59 vs. 1.11μIU/mL) concentrations compared with G, but only tended to increase glucose and insulin concentrations compared with 2G. Propylene glycol increased AUC for glucose (1,444 vs. 94.3mg/dL) and insulin (326 vs. 6.58min×μIU/mL) compared with G, and tended to increase insulin AUC compared with 2G. Propylene glycol was not different from GPG for glucose, insulin, or BHBA responses. Propylene glycol decreased plasma BHBA concentration (-10.3 vs. -4.21mg/dL) and increased BHBA AUC (-1,578 vs. -1.42min ×mg/dL) compared with G, but not compared with 2G. In general, and compared with G, GPG decreased plasma NEFA concentrations after infusions and PG decreased plasma NEFA concentrations early but not late after infusions. We conclude that a 300-mL dose of PG is more effective at increasing plasma glucose concentration than G and at least as effective as 600mL of G or a combination of G and PG when administered in the cranial reticulorumen. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Conventional insulin vs insulin infusion therapy in acute coronary syndrome diabetic patients

PubMed Central

Arvia, Caterina; Siciliano, Valeria; Chatzianagnostou, Kyriazoula; Laws, Gillian; Quinones Galvan, Alfredo; Mammini, Chiara; Berti, Sergio; Molinaro, Sabrina; Iervasi, Giorgio

2014-01-01

AIM: To evaluate the impact on glucose variability (GLUCV) of an nurse-implemented insulin infusion protocol when compared with a conventional insulin treatment during the day-to-day clinical activity. METHODS: We enrolled 44 type 2 diabetic patients (n = 32 males; n = 12 females) with acute coronary syndrome (ACS) and randomy assigned to standard a subcutaneous insulin treatment (n = 23) or a nurse-implemented continuous intravenous insulin infusion protocol (n = 21). We utilized some parameters of GLUCV representing well-known surrogate markers of prognosis, i.e., glucose standard deviation (SD), the mean daily δ glucose (mean of daily difference between maximum and minimum glucose), and the coefficient of variation (CV) of glucose, expressed as percent glucose (SD)/glucose (mean). RESULTS: At the admission, first fasting blood glucose, pharmacological treatments (insulin and/or anti-diabetic drugs) prior to entering the study and basal glycated hemoglobin (HbA1c) were observed in the two groups treated with subcutaneous or intravenous insulin infusion, respectively. When compared with patients submitted to standard therapy, insulin-infused patients showed both increased first 24-h (median 6.9 mmol/L vs 5.7 mmol/L P < 0.045) and overall hospitalization δ glucose (median 10.9 mmol/L vs 9.3 mmol/L, P < 0.028), with a tendency to a significant increase in first 24-h glycaemic CV (23.1% vs 19.6%, P < 0.053). Severe hypoglycaemia was rare (14.3%), and it was observed only in 3 patients receiving insulin infusion therapy. HbA1c values measured during hospitalization and 3 mo after discharge did not differ in the two groups of treatment. CONCLUSION: Our pilot data suggest that no real benefit in terms of GLUCV is observed when routinely managing blood glucose by insulin infusion therapy in type 2 diabetic ACS hospitalized patients in respect to conventional insulin treatment PMID:25126402

Intravenous nicotine self-administration and cue-induced reinstatement in mice: Effects of nicotine dose, rate of drug infusion and prior instrumental training

PubMed Central

Fowler, Christie D.; Kenny, Paul J.

2011-01-01

Intravenous nicotine self-administration is the most direct measure of nicotine reinforcement in laboratory animals, but this procedure has proven difficult to establish in mice. We found that stable responding for nicotine in C57BL6/J mice was facilitated by prior instrumental training for food reward, initial exposure of mice to a lower unit dose of nicotine (0.03 mg/kg/infusion) before access to higher doses, a slower rate of drug delivery (3-sec versus 1-sec infusion), consistency in schedule of daily testing, and low extraneous noise during testing. Under these conditions, we found that mice lever-pressing for nicotine (0.03–0.4 mg/kg/infusion; 60-min test sessions) under a fixed-ratio 5 time-out 20-sec (FR5TO20) reinforcement schedule consumed the drug according to an inverted ‘U’-shaped dose-response curve. Mice switched their responding onto a previously non-reinforced lever to continue earning nicotine infusions when the active/inactive lever assignment was reversed. The nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine decreased responding for nicotine, but not food rewards, verifying that nAChRs regulate nicotine self-administration in mice. The cue-light paired with nicotine delivery did not support responding when delivered independently of nicotine infusions, further verifying that mice responded selectivity for the drug. Nicotine-seeking responses extinguished when nicotine infusions and the cue-light were withheld, and exposure to the cue-light reinstated responding. Finally, mice without prior instrumental food training acquired stable responding for nicotine under the FR5TO20 schedule, but required a greater number of sessions. These data demonstrate that nicotine is an effective reinforcer in mice and establish conditions under which the drug is reliably self-administered by mice. PMID:21640128

Comparative effects of glycerol and Urografin on cochlear blood flow and serum osmolarity.

PubMed

Noi, O; Makimoto, K

1998-09-01

Glycerol, an osmotic diuretic, has been used for the diagnosis and treatment of endolymphatic hydrops. Hearing improvements in hydropic ears are attributed to its dehydrating effect. In addition to this effect, glycerol also increases cochlear blood flow. Urografin, another hyperosmotic agent used for vasography, is similarly known to increase local blood flow. The present study compared these two hyperosmotic agents, glycerol and Urografin, in their effects on cochlear blood flow and serum osmolarity. Laser Doppler flowmetry on the lateral wall of the cochlea revealed that the increase in cochlear blood flow with a 30-min infusion (0.025 ml/min) of 76% Urografin continued for a longer time than with a 30-min infusion (0.025 ml/min) of 50% (v/v) glycerol. The significant increases appeared at 20 and 30 min after the infusion with the former; 10, 20, 30, 40, 50 and 60 min after the infusion with the latter. Intravenous infusion of these agents also caused elevation in serum osmolarity. This elevation was appreciably greater with Urografin infusion (maximal increase: about 30 mOsm on average) than with glycerol infusion (maximal increase: about 6 mOsm on average), and the former elevation appeared to be longer lasting than the latter. These differences were ascribed to differences between glycerol and Urografin with respect to the creation of an osmotic gradient across the capillary walls of cochlear blood vessels. Since glycerol penetrates the interstitial space and moves into inner ear fluids, the gradient may decline faster. It would be assumed that a higher concentration of the hyperosmotic agent in the capillary blood causes more vasodilatation and lowering of blood viscosity. Alternatively, direct action of these agents on the vascular wall may affect some biological processes, leading to vasodilatation in different degrees and durations with different agents. Hearing improvement with glycerol administration in hydropic ears was also discussed from the perspective of cochlear blood flow.

Prolonged infusion versus intermittent boluses of β-lactam antibiotics for treatment of acute infections: a meta-analysis.

PubMed

Teo, Jocelyn; Liew, Yixin; Lee, Winnie; Kwa, Andrea Lay-Hoon

2014-05-01

The clinical advantages of prolonged (extended/continuous) infusion remain controversial. Previous studies and reviews have failed to show consistent clinical benefits of extending the infusion time. This meta-analysis sought to determine whether prolonged β-lactam infusions were associated with a reduction in mortality and improvement in clinical success. A search of PubMed, EMBASE and The Cochrane Library for randomised controlled trials (RCTs) and observational studies comparing prolonged infusion with intermittent bolus administration of the same antibiotic in hospitalised adult patients was conducted. Primary outcomes evaluated were mortality and clinical success. A total of 29 studies with 2206 patients (18 RCTs and 11 observational studies) were included in the meta-analysis. Compared with intermittent boluses, use of prolonged infusion appeared to be associated with a significant reduction in mortality [pooled relative risk (RR) = 0.66, 95% confidence interval (CI) 0.53-0.83] and improvement in clinical success (RR = 1.12, 95% CI 1.03-1.21). Statistically significant benefit was supported by non-randomised studies (mortality, RR = 0.57, 95% CI 0.43-0.76; clinical success, RR = 1.34, 95% CI 1.02-1.76) but not by RCTs (mortality, RR = 0.83, 95% CI 0.57-1.21; clinical success, RR = 1.05, 95% CI 0.99-1.12). The positive results from observational studies, especially in the face of increasing antibiotic resistance, serve to justify the imperative need to conduct a large-scale, well-designed, multicentre RCT involving critically ill patients infected with high minimum inhibitory concentration pathogens to clearly substantiate this benefit. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Effect of increasing Helicobacter pylori ammonia production by urea infusion on plasma gastrin concentrations.

PubMed Central

Chittajallu, R S; Neithercut, W D; Macdonald, A M; McColl, K E

1991-01-01

It has been proposed that the hypergastrinaemia in subjects with Helicobacter pylori infection is caused by the action of the ammonia produced by the organism's urease activity on the antral G cells. To investigate this hypothesis we examined the effect on plasma gastrin of increasing the bacterium's ammonia production by infusing urea intragastrically to eight H pylori positive duodenal ulcer patients. After a 60 minute control intragastric infusion of dextrose solution at 2 ml/minute, a similar infusion containing urea (50 mmol/l) was continued for four hours. During the urea infusion, the median gastric juice urea concentration rose from 1.1 mmol/l (range 0.3-1.6) to 15.5 mmol/l (range 7.9-21.3) and this resulted in an increase in the ammonium concentration from 2.3 mmol/l (range 1.3-5.9) to 6.1 mmol/l (range 4.2-11.9) (p less than 0.01). This appreciable rise in ammonia production did not result in any change in the plasma gastrin concentration. The experiment was repeated one month after eradication of H pylori, at which time the median basal gastrin was 20 ng/l (range 15-25), significantly less than the value before eradication (30 ng/l range 15-60) (p less than 0.05). On this occasion, the gastric juice ammonium concentration was considerably reduced at 0.4 mmol/l (range 0.1-0.9) and the urea infusion did not raise the ammonium concentration or change the plasma gastrin concentration. In conclusion, augmenting H pylori ammonia production does not cause any early change in plasma gastrin. PMID:1991633

Beta-endorphin-induced inhibition and stimulation of insulin secretion in normal humans is glucose dependent.

PubMed

Giugliano, D; Cozzolino, D; Salvatore, T; Torella, R; D'Onofrio, F

1988-09-01

This study evaluated the effect of human beta-endorphin on pancreatic hormone levels and their responses to nutrient challenges in normal subjects. Infusion of 0.5 mg/h beta-endorphin caused a significant rise in plasma glucose concentrations preceded by a significant increase in peripheral glucagon levels. No changes occurred in the plasma concentrations of insulin and C-peptide. Acute insulin and C-peptide responses to intravenous pulses of different glucose amounts (0.33 g/kg and 5 g) and arginine (3 g) were significantly reduced by beta-endorphin infusion (P less than .01). This effect was associated with a significant reduction of the glucose disappearance rates, suggesting that the inhibition of insulin was of biological relevance. beta-Endorphin also inhibited glucose suppression of glucagon levels and augmented the glucagon response to arginine. To verify whether the modification of prestimulus glucose level could be important in these hormonal responses to beta-endorphin, basal plasma glucose concentrations were raised by a primed (0.5 g/kg) continuous (20 mg kg-1.min-1) glucose infusion. After stabilization of plasma glucose levels (350 +/- 34 mg/dl, t = 120 min), beta-endorphin infusion caused an immediate and marked increase in plasma insulin level (peak response 61 +/- 9 microU/ml, P less than .01), which remained elevated even after the discontinuation of opioid infusion. Moreover, the acute insulin response to a glucose pulse (0.33 g/kg i.v.) given during beta-endorphin infusion during hyperglycemia was significantly higher than the response obtained during euglycemia (171 +/- 32 vs. 41 +/- 7 microU/ml, P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in arterial stiffness during continued infliximab treatment in patients with inflammatory arthropathies.

PubMed

Angel, Kristin; Provan, Sella Aarrestad; Hammer, Hilde Berner; Mowinckel, Petter; Kvien, Tore Kristian; Atar, Dan

2011-08-01

Chronic inflammatory arthropathies such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) are associated with an increased risk of cardiovascular disease. TNF-α antagonists may improve vascular function in these patients and thus be beneficial with regard to cardiovascular disease. This study evaluated arterial stiffness and disease activity between two infusions with a TNF-α antagonist (infliximab) in patients with inflammatory arthropathies on long-term infliximab therapy. Augmentation index (AIx), aortic pulse wave velocity (aPWV), and disease activity were measured in 17 patients with RA, AS, or PsA who had been treated with infliximab for at least 12 months. The patients were examined immediately before their infliximab infusion and thereafter every 10th day until their next infusion scheduled at week 4-8. AIx and aPWV did not change during the period between two infliximab infusions. The patients had a temporary improvement in the general disease activity assessed on visual analogue scales by the patients (P = 0.04) and the investigator (P = 0.02) after the infusion. In the group of patients with RA, the Disease Activity Score (DAS28) changed significantly in a similar manner (P = 0.003). C-reactive protein and erythrocyte sedimentation rate remained unchanged. Infliximab infusions did not alter aortic pulse wave velocity or augmentation index in patients with inflammatory arthropathies who were on long-term infliximab therapy. Reductions in the general disease activity and DAS28 were not reflected in alterations of aortic stiffness or augmentation index. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.