Drug Infusion System Manifold Dead-Volume Impacts the Delivery Response Time to Changes in Infused Medication Doses In Vitro and Also In Vivo in Anesthetized Swine

2013 ◽  
Vol 117 (6) ◽  
pp. 1313-1318 ◽  
Author(s):  
Mark A. Lovich ◽  
Matthew G. Wakim ◽  
Abraham Wei ◽  
Michael J. Parker ◽  
Mikhail Y. Maslov ◽  
...  
Keyword(s):  
Response Time ◽  
Dead Volume ◽  
Drug Infusion ◽  
Infusion System

Computer Control of Drug Delivery by Continuous Intravenous Infusion

2015 ◽  
Vol 122 (3) ◽  
pp. 647-658 ◽  
Author(s):  
Michael J. Parker ◽  
Mark A. Lovich ◽  
Amy C. Tsao ◽  
Abraham E. Wei ◽  
Matthew G. Wakim ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Steady State ◽  
Intravenous Infusion ◽  
Computer Control ◽  
Dead Volume ◽  
Dominant Factor ◽  
Drug Infusion ◽  
Temporal Lags

Abstract Background: Intravenous drug infusion driven by syringe pumps may lead to substantial temporal lags in achieving steady-state delivery at target levels when using very low flow rates (“microinfusion”). This study evaluated computer algorithms for reducing temporal lags via coordinated control of drug and carrier flows. Methods: Novel computer control algorithms were developed based on mathematical models of fluid flow. Algorithm 1 controlled initiation of drug infusion and algorithm 2 controlled changes to ongoing steady-state infusions. These algorithms were tested in vitro and in vivo using typical high and low dead volume infusion system architectures. One syringe pump infused a carrier fluid and a second infused drug. Drug and carrier flowed together via a manifold through standard central venous catheters. Samples were collected in vitro for quantitative delivery analysis. Parameters including left ventricular max dP/dt were recorded in vivo. Results: Regulation by algorithm 1 reduced delivery delay in vitro during infusion initiation by 69% (low dead volume) and 78% (high dead volume). Algorithmic control in vivo measuring % change in max dP/dt showed similar results (55% for low dead volume and 64% for high dead volume). Algorithm 2 yielded greater precision in matching the magnitude and timing of intended changes in vivo and in vitro. Conclusions: Compared with conventional methods, algorithm-based computer control of carrier and drug flows can improve drug delivery by pump-driven intravenous infusion to better match intent. For norepinephrine infusions, the amount of drug reaching the bloodstream per time appears to be a dominant factor in the hemodynamic response to infusion.

In Vivo vs. In Vitro Response Time of Trancutaneous Po2Electrodes A comparison of four devices in newborn infants

1978 ◽  
Vol 22 ◽  
pp. 40-48 ◽  
Author(s):  
H. T. Versmold ◽  
O. Linderkamp ◽  
K. H. Stuffer ◽  
M. Holzmann ◽  
K. P. Riegel
Keyword(s):  
Response Time ◽  
Newborn Infants ◽  
In Vitro Response

scholarly journals Modulation of FoxO1 Expression by miR-21 to Promote Growth of Pancreatic Ductal Adenocarcinoma

2015 ◽  
Vol 35 (1) ◽  
pp. 184-190 ◽  
Author(s):  
Weifeng Song ◽  
Qi Li ◽  
Lei Wang ◽  
Liwei Wang
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Underlying Mechanism ◽  
Ductal Adenocarcinoma ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Primary Tumors ◽  
Protein Levels ◽  
Infusion System

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal primary tumors in humans, with undetermined tumorigenesis. Although previous work by us, and by others, has clearly demonstrated an involvement of miR-21 in the growth of PDAC, the underlying mechanism has not been clarified. Methods: Here we analyzed the regulation of FoxO1 by miR-21 in vitro and in vivo, using luciferase-reporter assay and pancreatic intraductal infusion of antisense of miR-21, respectively. Results: We found that overexpression of miR-21 in PDAC cells decreased FoxO1 protein levels, whereas inhibition of miR-21 increased FoxO1 levels. Further, miR-21 bound to FoxO1 mRNA to prevent its translation through its 3'UTR. Moreover, administration of antisense of miR-21 through an intraductal infusion system significantly decreased miR-21 levels and increased FoxO1 levels in implanted PDAC, resulting in a significant decrease in PDAC growth. Conclusion: Taken together, our data highlight miR-21/FoxO1 axis as a novel therapeutic target for inhibiting the growth of PDAC.

scholarly journals Evidence for early recruitment of granulocyte precursors during high- dose methotrexate infusions in mice

Blood ◽  
1976 ◽  
Vol 48 (2) ◽  
pp. 301-307 ◽  
Author(s):  
HM Pinedo ◽  
BA Chabner ◽  
DS Zaharko ◽  
JM Bull
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Bone Marrow Cells ◽  
Stem Cell Population ◽  
High Dose ◽  
Mouse Bone Marrow ◽  
Drug Infusion ◽  
High Concentrations

Abstract The effects of constant exposure to high concentrations of methotrexate in vivo on the committed stem cell (CFU-C) were studied by in vitro culture of mouse bone marrow. Bone marrow samples were obstained from animals receiving a continuous infusion, and were cultured in a methotrexate-free semisolid gel system. The effects of methotrexate infusion on the pluripotent stem cell population (CFU-S) were studied as well. Constant exposure to 10(-5) M methotrexate produced a rapid decrease in total nucleated cells per femur, reaching 35% of control at 12 hr and remaining at approximately this level throughout 48 hr of drug infusion. A decrease in the number of both CFU-C and CFU-S per femur was observed, which paralleled the drop in nucleated cells during the first 24 hr. However, in contrast to an additional drop in the number of CFU-S, an increase of CFU-C number per femur was observed from 24 to 48 hr. These data indicated a self-limited cell kill of nucleated bone marrow cells, and suggested recruitment of CFU-C from the CFU-S pool between 24 and 48 hr of infusion despite continued methotrexate infusion.

scholarly journals Drug Flow Through Clinical Infusion Systems: How Modeling of the Common-volume Helps Explain Clinical Events

2017 ◽  
Vol 2 (2) ◽  
Author(s):  
Mark A. Lovich ◽  
Robert A. Peterfreund
Keyword(s):  
Drug Delivery ◽  
Computational Simulation ◽  
Hemodynamic Instability ◽  
Infusion Therapy ◽  
Drug Infusion ◽  
Infusion Systems ◽  
The Common ◽  
The Impact ◽  
Infusion System

AbstractThis review aims to describe analytic models of drug infusion that demonstrate the impact of the infusion system common-volume on drug delivery. The common-volume of a drug infusion system is defined as the volume residing between the point where drug and inert carrier streams meet and the patient’s blood. We describe 3 sets of models. The first is quantitative modeling which includes algebraic mathematical constructs and forward-difference computational simulation. The second set of models is with in vitro benchtop simulation of clinical infusion system architecture. This modeling employs devices including pumps, manifolds, tubing and catheters used in patient care. The final set of models confirms in vitro findings with pharmacodynamic endpoints in living large mammals. Such modeling reveals subtle but important issues inherent in drug infusion therapy that can potentially lead to patient instability and morbidity. The common-volume is an often overlooked reservoir of drugs, especially when infusions flows are slowed or stopped. Even with medications and carriers flowing, some mass of drug always resides within this common-volume. This reservoir of drug can be inadvertently delivered into patients. When infusions are initiated, or when dose rate or carrier flow is altered, there can be a significant lag between intended and actual drug delivery. In the case of vasoactive and inotropic drug infusions, these unappreciated time delays between intended and actual drug delivery can lead to iatrogenic hemodynamic instability. When a drug infusion is discontinued, drug delivery continues until the common-volume is fully cleared of residual drug by the carrier. The findings from all 3 sets of models described in this review indicate that minimizing the common-volume of drug infusion systems may enhance patient safety. The presented models may also be configured into teaching tools and possibly point to technological solutions that might mitigate sources of iatrogenic patient lability.

Effects of arterial hypoxia and isoproterenol on in vitro postnatal intestinal circulation

1988 ◽  
Vol 255 (5) ◽  
pp. H1144-H1148 ◽  
Author(s):  
P. T. Nowicki ◽  
C. E. Miller ◽  
S. E. Haun
Keyword(s):  
Age Groups ◽  
Response Characteristic ◽  
Similar Degree ◽  
Drug Infusion ◽  
Vascular Regulation ◽  
Relative Inability ◽  
Isoproterenol Infusion ◽  
Intestinal Circulation

We have previously speculated that intestinal vasodilation and hyperemia that occur in response to moderate arterial hypoxia in newborn swine in vivo are mediated by factors intrinsic to the intestinal circulation. To test this speculation, we vascularly perfused in vitro loops of jejunum from postnatal swine with control (PO2 98 +/- 4 mmHg) and hypoxic (PO2 38 +/- 2 mmHg) blood obtained from donor swine. In response to hypoxic perfusion, jejunal vascular resistance decreased 12 +/- 2, 13 +/- 3, 33 +/- 5, and 42 +/- 3% in in vitro loops from 1-, 7-, 14-, and 30-day-old swine, respectively, whereas jejunal oxygen uptake decreased 53 +/- 6, 29 +/- 6, 31 +/- 4, and 13 +/- 6% in these age groups. To clarify whether this age-dependent vasodilation was unique to the stimulus of arterial hypoxia or a response characteristic of the postnatal swine intestine to other vasodilator stimuli, we also determined the effect of intra-arterial isoproterenol infusion at rates of 0.01, 0.1, and 1.0 micrograms/min on jejunal hemodynamics and oxygenation in vitro. In jejunal loops taken from 7- and 30-day-old swine, isoproterenol caused a similar degree of vasodilation at each drug-infusion rate. We conclude that vasodilation of the postnatal swine intestine in response to moderate arterial hypoxia is mediated, at least in part, by intrinsic vascular regulation. We speculate that the age dependency of hypoxic vasodilation may reflect a relative inability of the intestine from very young swine to respond to the stimulus of arterial hypoxia.

Fast-responding flow-independent blood gas catheter for oxygen measurement

1980 ◽  
Vol 48 (2) ◽  
pp. 376-381 ◽  
Author(s):  
J. S. Lundsgaard ◽  
B. Jensen ◽  
J. Gronlund
Keyword(s):  
Response Time ◽  
Blood Gas ◽  
Background Ratio ◽  
Time Flow ◽  
Analytic Expressions ◽  
Flow Dependency ◽  
Oxygen Measurement

Analytic expressions were derived for the response time, flow dependency, and signal-to-background ratio of blood gas catheters. These expressions were utilized to optimize the design of a new catheter. The catheter was tested in vitro and in vivo, and shown to be fast responding and practically flow independent, with an acceptable signal-to-background ratio.

scholarly journals Formulation and Evaluation of Parenteral Sustained Release Microspheres of Diclofenac Sodium

2003 ◽  
Vol 71 (2) ◽  
pp. 101-111
Author(s):  
C. Sajeev ◽  
R. Archna ◽  
V. Gupta ◽  
A. Sobti ◽  
R. Saha
Keyword(s):  
Sustained Release ◽  
Response Time ◽  
Diclofenac Sodium ◽  
In Vitro Release ◽  
Tail Flick ◽  
Duration Of Action ◽  
Sustained Release Formulation ◽  
Vitro Release

The aim of this study was to formulate and evaluate microsphere based depot type parenteral sustained release formulation of diclofenac sodium (DFS). Drug was formulated in the form of microspheres, using varying proportion of ethylcellulose (EC) as the retardant material to extend the release, by phase separation-coacervation technique. The in vitro release pattern of the designed formulations was studied using modified Franz diffusion cell. In vivo pharmacodynamic study was carried out by determining the index of analgesia (increase in response time to thermal stress as percentage of basal response time). Tail flick method was employed to measure both the degree of analgesia and its duration of action. The prepared microspheres were white, free flowing, and spherical in shape with a mean particle size of 50 μm. In vitro release study of the micro-spheres in aqueous media was found to extend the release of DFS beyond 24 hours with DFS and EC ratio 1:3. The plot of log percentage remaining to be released vs. time gave a linear relationship indicating first-order release kinetics. The in vitro release rate constant (Kr) for different microspheres varied between 0.1448 hr-1 and 0.0256 hr-1. A good correlation was obtained between K, and proportion of EC in the microspheres. In vivo pharmacodynamic studies indicated that the duration of analgesic action is prolonged beyond 24 hrs in case of microsphere products of 1:3 ratio of DFS to EC, whereas administration of marketed parenteral preparation showed activity only up to 11hrs. Also, a good correlation was obtained between analgesic activity in vivo and cumulative percentage of drug release from the formulations.

In Vitro and In Vivo Performance of a Pre-Filled, Electrochemically-Actuated Infusion System

2015 ◽  
Vol 33 (1) ◽  
pp. 83-91 ◽  
Author(s):  
Assaf Shaked ◽  
Ella Tenenbaum-Koren ◽  
Jacob Atsmon ◽  
Peter Noymer
Keyword(s):  
Infusion System
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