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

Lovich, Mark A.; Wakim, Matthew G.; Wei, Abraham E.; Parker, Michael; Maslov, Mikhail Y.; Pezone, Matthew J.; Tsukada, Hisashi; Peterfreund, Robert A.

doi:10.1213/ane.0b013e3182a76f3b

Cited by 20 publications

(13 citation statements)

References 6 publications

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“…A novel drug infusion manifold (Edelveiss Multiline, Doran International, Toussieu, France) wherein all the medications flow coaxially down a multi-channeled tube and only meet at the distal tip, thus eliminating the manifold contribution to infusion system common-volume ( Figure 4B), was connected to the single lumen catheter (low V = 0.22 mL). In vitro data show that drug emerges from the infusion system and reaches steady state much faster with the low compared to the high common volume system ( Figure 5A) [30]. When the drug infusion is turned off, drug delivery ends within minutes with the low commonvolume infusion system, whereas with the high volume system, drug may still be delivered for over 20 min.…”

Section: In Vivo Modelsmentioning

confidence: 99%

“…In vitro data have been confirmed in vivo using large animal models, which allow measurement of pharmacodynamic endpoints. The simplest of these in vivo models utilizes infusions of catecholamines such as epinephrine or norepinephrine which have easily measured endpoints of blood pressure or indices of myocardial contractility (max dP/dt) [30]. In a series of in vivo experiments using healthy anesthetized adolescent swine, epinephrine was infused at 0.1 mcg/kg/ min (3 mL/hr) for 30 min and then turned off.…”

Section: In Vivo Modelsmentioning

confidence: 99%

“…In vivo data demonstrate that these delays in drug delivery are not just theoretical [30]. Biologic response was significantly delayed by using a high common- (A) The common-volume is modeled as a series of small discrete nodes, each with finite volume and homogenous concentrations.…”

Section: In Vivo Modelsmentioning

confidence: 99%

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

Lovich

Peterfreund

2017

Pharmaceutical Technology in Hospital Pharmacy

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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.

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Section: In Vivo Modelsmentioning

confidence: 99%

Section: In Vivo Modelsmentioning

confidence: 99%

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

Lovich

Peterfreund

2017

Pharmaceutical Technology in Hospital Pharmacy

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“…The architecture of the manifold impacts an in vivo biological response and drug delivery rate during changes in drug infusion rate set at the pump [74]. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 11 Plug-Flow model.…”

Section: Common Dead Volume Of Drugs Delivered Simultaneously and Conmentioning

confidence: 99%

Criteria for choosing an intravenous infusion line intended for multidrug infusion in anaesthesia and intensive care units

Maiguy-Foinard

Genay²,

Lannoy

et al. 2017

Anaesthesia Critical Care & Pain Medicine

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“…We and others have shown in a series of in vitro experiments how drug delivery rate does not always match intended dose. [1][2][3][4][5][6][7] By implication, infused drugs that enter into a manifold to be combined with an inert drug carrier flow would then require an interval of time to traverse the common volume (also known as the dead volume) before entering the patient's blood. Common volume is defined as the volume between the point where the drug and carrier streams meet and the patient's blood.…”

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confidence: 99%

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

et al. 2016

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Background 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. Methods 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. Results 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. Conclusions 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.

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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

Abstract: The architecture of the manifold impacts the in vivo biologic response, and the drug delivery rate, to changes in drug infusion rate set at the pump.

Cited by 20 publications

References 6 publications

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

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

Criteria for choosing an intravenous infusion line intended for multidrug infusion in anaesthesia and intensive care units

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

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