Infusing Liquids Into Veins And Other...
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Infusing LiquidsInto Veins
And Other Tissues
Header
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Infusing LiquidsInto Veins
And Other Tissues
Copyright
© 2004 James H Philip, all rights reserved.No part of this lecture can be used for anything but
learning without express permission
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Infusing LiquidsInfusing Liquidsin Veinsin Veins
and Other Tissuesand Other TissuesJames H. Philip, ME(E), MD, CCE
Anesthesiologist and Director of BioengineeringDepartment of Anesthesia
Brigham and Women's HospitalAssociate Professor of Anesthesia
Harvard Medical School
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Collaborators at BWH
Beverly Philip MDJohn Fox MDDan Raemer PhDJohn Lehr PhDDavid Joseph MDJP Warner MDGL Brodsky MDTom Thornhill MDDavid Gissen MDSanjay Datta MDDavid Leith MDRichard Morris MDDavid Scott MD
Tulie Canaan PhDMaryanne Palleiko RNLeonard Lind MDJohn Stelling MDAngelo Rocco MDRobert Boas MDNile Hughs MDMark Johnson MDDavid Goodie MDXin Bao Xi PhDStewart Dunbar MDIggy Calalang MS
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History
Clinical IV SystemsConduits - tubing and catheters
VeinsCollapsible tubes of latex
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History of Clinical IV Systems1960 Common use - Elevated bottle, roller clamp.
Flow - Visual measure, manual control1966 La Cour & Ferechak -
Drops are an inaccurate volume measure.Size = F{Temp,Composition, Orifice diameter, Orifice shape}
1974 Flack & Whyte -Tubing creeps (cold-flow of plastic), varies flow, usually decreases flow
1984 Philip & Philip -Constant high pressure provides high flow
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Studies of Fluid Flow in Veins
1912 Starling -Used tubing collapse to produce constant pressureUsed for afterload on the heartIncorrectly claimed "resistance"Produced constant pressure - "Starling Resistor"
1941-1963 Numerous Authors -Physical model for vein collapsePenrose Drain
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Studies of Fluid Flow in Veins
1963 Permutt and Riley -Defined “Critical Closing Pressure”Showed Flow is independent of pressure dropCoined the name “Vascular Waterfall”
1977 Shapiro (at MIT) -Developed “One dimensional theory ofsteady flow in thin-walled tubes partly collapsedby negative intramural pressure.Explained the collapse of rubber tubes
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IronyResearchers studied latex tubesLatex tubes (Penrose Drains) don’t
collapse
That’s why they’re “surgical drains”
Veins do collapse completelyIn vivo and in vitro
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Compress a Vein
Veins
Collapse
Completely
Pressure
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Compress Tubing
Pressure
Tubes
Collapse
Incompletely
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Compress Tubing
Pressure
Tubes
Collapse
IncompletelyTwo
TubesRemain
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Make Tubing CollapseTwo Small
Tubes
Filled withSiliconeClose
Completely
Big TubeCollapses
Completely
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Latex Tubes vs. VeinsLatex Tubes (Penrose Drains)
Complex Behavior Collapse Incompletely1 big tube becomes two small tubes
VeinsSimple BehaviorCollapse Completely
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VeinsCan be collapsed
Can be compressed
Cartoon depiction
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Vein
Require additional pressure for flowPvein = P0 + R F
If compressed, require opening pressurePvein = P0 = Tourniquet Pressure
Can open widely
Can open partly
Can collapse completelyWould require pressure
Pvein
Ptourn
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Vein
Pvein = R FPvein
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Vein
Require additional pressure for flowPvein = P0 + R F
If compressed, require opening pressurePvein = P0 = Tourniquet Pressure
Pvein
Ptourn
Pvein = R F
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Pressure-Flow Relationship (PFR)and appearance of a VeinFlow
PressurePo-
G = ∆ Pressure
∆ Flow
AppearanceDescriptioncollapsed
no flowopeningfluttering Fully open flowing fast
= Conductance = 1 / Resistance
(transmural = Pin- Poot )
F = 0 if P < Po
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Non- Linearity
Another one Grand Rounds 2 weeks agoVaporizer with a liquid that almost boilsPhase transition or a State Transition Liquid to Gas
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openingfluttering
Fully open
flowing fast
PoR =
∆ Pressure
∆ Flow = Resistance = 1 / Conductance
-
Flow
Pressure
F = 0 if P < Po
Flow - Pressure Relationship (FPR)and appearance of a Vein
collapsed
no flow
Appearance
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The Pressure-Flow Relationshipand Clinical Systems
SciencePhilip JH. Model of the Physics andPhysiology of Fluid Administration. Journal of Clinical Monitoring.1989; 5:123-134.
Easy read: ftp://jphilip.bwh.harvard.edu/technology/fluids/Philip JH. Intravenous Access and Delivery Principles. In: Rogers MC, Tinker JH,Covino BG, Longnecker DE.Principles and Practice of Anesthesiology.St Louis: Mosby. 1992: 1183-1196.
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Model ElementsPressure Source - Elevated Bag (P=ht)Flow Source - Pump
Resistors - tubing, catheter, vein, roller clamp, tissue
Obstructers - Starling Resistors Tourniquet, BP Cuff,Compressed Veins, water falls
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Graphs of relationshipsbetween P and F
Pressure
Flow
Flow
Pressure
Elevated bagand Flow Measure(drop rate)
Pressure-driven
PFR
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Graphs of relationshipsbetween P and F
Pressure
Flow
Flow
Pressure
Infusion Pumpand Pressure Transducer
Flow-driven
FPR
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Pressure = free-air surface height above reference levelminus (-) height of air gaps.
Po P = Po = (at any flow, + or -) = Bag Height
P(mmHg )
F ( mL / hr )
Pressure Source - Elevated Bag
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Flow Source - Infusion Pump
F = Fset
P(mmHg )
F ( L / hr )
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Flow Source - Infusion PumpInfuse at set rate (e.g., 0.1 - 999 mL/hr)
Despite impedimentstubing, catheter, patientR = 2, 6-17, 5-100 mmHg/L/hr
May require or provide high pressure5 psi = 250 mmHg, 10 psi = 500 mmHg
1 psi = 50 mmHg - rememberMay convert infiltration to injury
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Linear peristaltic mechanismflow comprised of one microliter volumes
Pressure TransducerJust distal to pumping mechanismpresses against in-line pressure-sensing diskDisk is in IV tubing
P ± 2 mm Hg accuracy (mmHg) with or without flowR units are P / F = mmHg/L/hr = mmHg • hr / LIVAC Alaris Model 560 and later
Pressure-Monitoring Pump
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500 100 200 300150 2500
5
10
15
20
R = Resistance [mmHg/L/hr]
R = ∆ P∆ F
Resistors and Resistance
Pre
ssur
e (m
mH
g)
F (m L / hr )
F ( L / hr )0.30.20.1
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500 100 200 300150 2500
5
10
15
20
R = Resistance [mmHg/L/hr]
F (m L / hr )
R = ∆ P∆ F
Resistors and Resistance
Pre
ssur
e (m
mH
g)
F ( L / hr )0.30.20.1
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500 100 200 300150 2500
5
10
15
20
R = Resistance [mmHg/L/hr]
R = ∆ P∆ F
∆ P
= Slope
Resistance = Slope of PFR
Pre
ssur
e (m
mH
g)
F (m L / hr )
F ( L / hr )0.30.20.1 ∆ F
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500 100 200 300150 2500
5
10
15
20
R = Resistance [mmHg/L/hr]
R = ∆ P∆ F
∆ P = 4
= Slope = 4 mmHg0.1 L/hr
= 40mmHgL/hr
7
3
Resistors resist flow
Pre
ssur
e (m
mH
g)
F (m L / hr )
F ( L / hr )0.30.1 0.2∆ F = 0.1 L/hr
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500 100 200 300150 250tubing(3)#16 (6)#18 (6)#20(17)
#22(34)
#24(66)
0
5
10
15
20catheters
R = Resistance [mmHg/L/hr]
F (mL / hr )
Catheters are Resistors
Pre
ssur
e (m
mH
g)
#Ga(R )mmHg
L/hr
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500 100 200 300150 250tubing(3)#16 (6)#18 (6)#20(17)
#22(34)
#24(66)
0
5
10
15
20catheters
R = Resistance [mmHg/L/hr]
#Ga(R )
F (mL / hr )
Tubings are Resistors
Pre
ssur
e (m
mH
g)
mmHg
L/hr
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500 100 200 300150 250tubing(3)#16 (6)#18 (6)#20(17)
#22(34)
#24(66)
0
5
10
15
20
roller clamp(800) (300)
catheters
R = Resistance [mmHg/L/hr]
F ( mL / hr )
Roller Clamps are Resistors
Pre
ssur
e (m
mH
g)
#Ga(R )mmHg
L/hr
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500 100 200 300150 250tubing(3)#16 (6)#18 (6)#20(17)
#22(34)
#24(66)
0
5
10
15
20
roller clamp(800) (300)
catheters
R = Resistance [mmHg/L/hr]veins (5-100)
vein (22)
F ( mL / hr )
Wideresistancerange
Veins are Resistors
Pre
ssur
e (m
mH
g)
#Ga(R )mmHg
L/hr
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Resistances in Series Add
Total Resistance = Sum of Individual Resistances
TubingCatheterRoller ClampOther DevicesPatient Vein
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Resistances in Series Add
Total Resistance =Sum of Individual Resistances(Units = mmHg/L/hr)
Tubing = 3Catheter = 6 - 16Roller Clamp = 0 or 800Other Devices are smallPatient Vein = 0 - 100, Average = 22
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Total Resistance
Dominated by patient veinAffected by tubing and catheter
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0 50 100 150 200 250 300
Normal VeinR = 22 mmHg/L/hr
Low resistance
F (m L / hr )
Veins are predominantly ResistorsP
ress
ure
(mm
Hg)
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0 50 100 150 200 250 300
Normal VeinR = 22 mmHg/L/hr
Po = CVP
Po
Low opening pressure
F ( mL / hr )
Veins have low Opening PressureP
ress
ure
(mm
Hg)
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Resistance to fluid flow 0 - 200 mmHg/L/hr
Opening pressure at zero flow
Opening pressure = PoObstructs veinDepends on tissue forces outside the veinStarling Resistor
Veins alter fluid flow two ways
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0
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0 50 100 150 200 250 300
With Tourniquet
Normal Vein
Po = Tourniquet pressure
R = 22 mmHg/mL/hr
R = 22 mmHg/mL/hrCVP
Po
Elevated opening pressure
F ( mL / hr )
Tourniquets obstruct veinsP
ress
ure
(mm
Hg)
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0
10
20
30
40
50
60
70
80
90
100
0 50 100 150 200 250 300
R = 22 mmHg/mL/hr
R = 22 mmHg/mL/hrCVP
Po
Elevated opening pressure
F ( mL / hr )
Fat compresses and obstructs veinsP
ress
ure
(mm
Hg)
PT
With Tourniquet
Normal Vein
PF = Fat pressure Obese Arm
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0
10
20
30
40
50
60
70
80
90
100
0 50 100 150 200 250 300
Pext = 0
Pext = 75
Pext = 10
Pext = 100
Pext = 50
Po = Pext
F ( mL / hr )
Opening pressure = Cuff Pressure, almostBP Cuffs obstruct veins
Pre
ssur
e (m
mH
g)
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020406080
100120140160180200220240260
0 100 200 300 400 500 600 700 800 900 1000
PO = 80 mmHg
F (mL/ hr )
Catheter malposition can obstruct veinsP
ress
ure
(mm
Hg)
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R tissue >> Rvein
Rtissue = 1125 ± 1376 (SD) RU
Rvein = 22 ± 20 (SD) RU
Tissue Resistance is large
Scott DA, Fox JA, Philip BK, Lind LJ, Cnaan T, Palleiko MA, Stelling JM, Philip JH. Detection of Intravenous Fluid Extravasation Using Resistance Measurements. J Clin Monit. 1996; 12:325-330.
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Distribution of vein resistance for 46 surgical patients
0
2
4
6
8
10
12
14
16
0 200
Distribution of Vein Resistance
100
Veins
RESISTANCE (mmHg/l/hr)
CO
UN
T
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Distributions of Vein and Tissue Resistances
0
2
4
6
8
10
12
14
16
Veins
0 200 400 600 800
Tissues
RESISTANCE (mmHg/l/hr)>1000
Distribution of Vein Resistance
Distribution of Tissue Resistance
CO
UN
T
More R
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100
200
300
400
500
00 100 200 300 400 500 600 700 800 900 1000
100
200
300
400
500
0
Normal vein R = 22, Po = 10
Infiltrated Tissue R = 500, Po = ?
Obstructed vein R = 22, Po = 80
F (m L / hr )
Normal Vein, Obstructed Vein, Infiltrated TissueP
ress
ure
(mm
Hg)
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100
200
300
400
500
00 100 200 300 400 500 600 700 800 900 1000
100
200
300
400
500
0
Normal vein R = 22, Po = 10
Obstructed vein R = 22, Po = 80
F (m L / hr )
Obstructed Vein and Infiltrated Tissuecan appear similar
Infiltrated Tissue R = 500At F = 200 here,Infiltrated Tissueand obstructed vein cannot bedistinguished
Pre
ssur
e (m
mH
g)
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Requirements to Monitor an IV infusion
FLOW - controlledPRESSURE - measuredor the reverseP - F RELATIONSHIP - analyzedRESISTANCE - computed as R = ∆P / ∆FOBSTRUCTING PRESSURE - measured as PoRESULTS - trended and analyzed
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Requirements to Monitor an IV infusionFLOW - controlledPRESSURE - measuredor the reverseP - F RELATIONSHIP - analyzedRESISTANCE - computed as R = ∆P / ∆FOBSTRUCTING PRESSURE - measured as PoRESULTS - trended and analyzedPATENT - J Philip.BWH Licensed to IVAC,1985PRODUCT - IVAC/Alaris Signature Edition
Monitors Resistance
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Alaris (IVAC) Signature Pumpmonitors Hydraulic Resistance
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Alaris (IVAC) Signature Pumpmonitors Hydraulic Resistance
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Present Clinical Applications
of ResistanceDevice evaluation (catheters, tubing,..)
Site AssessmentCatheter Size SelectionFluid Resuscitation OptimizationSpace Identification (epidural, axillary,..)
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Goodie DB, Philip JH, Is the IV obstructed or infiltrated? A simple clinical test. J Clin Monit. 1995; 11:47- 50
Site Assessment
R measured by eye - Bag Elevation
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R measured by eye - Bag Elevation
10 20 30 40
60 120
(drops/min)
(ml/hr) 180 2400
20
40
60
80
100
120Infiltrated
Obstructed
Flow
+10 cm
Tissue
Vein
R = ∆ P/∆ F
Goodie DB, Philip JH, Is the IV obstructed or infiltrated? A simple clinical test. J Clin Monit. 1995; 11:47- 50
Site A
sses
smen
t
Pre
ssur
e (c
mH
2O)
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R measured by Bag Elevationeven in the presence of a venous tourniquet
Goodie DB, Philip JH, Is the IV obstructed or infiltrated? A simple clinical test. J Clin Monit. 1995; 11:47- 50
10 20 30 40
60 120
(drops/min)
(ml/hr) 180 2400
20
40
60
80
100
120
+3 drops / min
+24 drops / min
Infiltrated
Obstructed
Flow
+10 cm
Tissue
Vein
R = ∆ P/∆ FP
ress
ure
(cm
H2O
)
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Choice of Catheter Size20 ga catheter allows a steady IV flow stream.
If flow is lower, vein is impeded or system is malfunctioning
When a 20 ga IV catheter produces low flow, the major flow impediment is probably the patient’s vein, not the IV catheter
Starting a second IV in a different vein increases flow more than placing a larger cannula because venous resistance dominates
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Choice of Catheter Size
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Which usually provides greater flow, One 14 g catheter or Two 20 g catheters in different veins?Two 20 gauge catheters !
One 14 g catheterR = R(14g) + R(vein) = 5 + 22 = 28
Two 20 g catheters: Each R = R(20g) + R(vein) = 17 + 22 = 392 in parallel, R = 39 / 2 = 19.5R is 1.4 times lower,Flow is 1.4 times as high = 40% higher
Goodie DB, Philip JH, An analysis of the effect of venous resistance on the performance of gravity-fed intravenous systems. J Clin Monit. 1994; 10: 222-226.
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Catheter size
“The only thing wrong with a 20 g catheter
is that it’s probably in a 20 g vein”
Goodie DB, Philip JH, An analysis of the effect of venous resistance on the performance of gravity-fed intravenous systems. J Clin Monit. 1994; 10: 222-226.
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High Flow ResuscitationPressure and resistance limit flow. Both should be optimizedResistance Lowering Sequence
Open Roller ClampsRemove interposing devices contributing to total resistance.
Removal Order (considering non-linearity)Remove coil liquid warmerChange catheter from 16 to 14 gaugeRemove check valve Change catheter from 14 to 12 gauge Replace regular tubing with wide bore tubing Change catheter from 12 to 10 gauge Remove stopcocks Remove 10 gauge catheter and insert sterile tubing in vein
Catheters usually cannot be changed Stopcocks need not be removed !
Philip JH, Philip BK. Prediction of flow capability in intravenous systems: implications for fluid resuscitation. J Clin Monit. 1990; 6:113-117.
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Viscosity Effects
Apparent Resistance is proportional to Viscosity
Goodie DB, Philip JH. Viscosities of commonly infused substances. BJA 1995; 74:491-492
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100
200
300
400
500
00 100 200 300 400 500 600 700 800 900 1000
100
200
300
400
500
0
Viscosity = ν = 54
32
1
R = P1000
F ( mL / hr )
Apparent Resistance is proportional to ViscosityP
ress
ure
(mm
Hg)
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RDCW = Rwater (1 + C2 /1000).
Fluid ViscosityWater 1.0Saline 1.0
5D W 1.03D10W 1.1D 20W 1.4D 30W 1.9D40 W 2.6D50W 3.5
Viscosities of Dextrose Solutions
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RDCW = Rwater (1 + C2 /1000).
D 0 W 1.00D30 W 2.00
43D W 3.00D 52W 4.00
Fluid Viscosity
Viscosities of Dextrose Solutions
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100
200
300
400
500
00 100 200 300 400 500 600 700 800 900 1000
100
200
300
400
500
0
Viscosity = ν = 54
32
1
R = P1000
D 52
D 43
D 30
D 0
F ( mL / hr )
It is easy to make liquids of varied viscosity
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Viscosity of Various Clinical Infusates
Goodie DB, Philip JH. BJA 1995; 74:491-492.
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Infusate ViscosityWater 1.00Hespan 3.655% Albumin 1.09Haemaccel (Hoechst U.K) 1.50Dextran 40 in saline 4.01Dextran 70 in saline 3.28Dextran 40 in D5 W 4.92Propofol 1.45Thiopental 1.03Intralipid 1.36D17 W 1.36Osmolyte (Gastric) 6.57
Goodie DB, Philip JH. BJA 1995; 74:491-492.
Viscosities of other infusates
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Infusate ViscosityWater 1.00Hespan 3.655% Albumin 1.09Haemaccel (Hoechst U.K) 1.50Dextran 40 in saline 4.01Dextran 70 in saline 3.28Dextran 40 in D5 W 4.92Propofol 1.45Thiopental 1.03Intralipid 1.36D17 W 1.36Osmolyte (Gastric) 6.57
Goodie DB, Philip JH. BJA 1995; 74:491-492.
Clinical
Viscosities of other infusates
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Infusate ViscosityWater 1.00Hespan 3.655% Albumin 1.09Haemaccel (Hoechst U.K) 1.50Dextran 40 in saline 4.01Dextran 70 in saline 3.28Dextran 40 in D5 W 4.92Propofol 1.45Thiopental 1.03Intralipid 1.36D17 W 1.36Osmolyte (Gastric) 6.57
Goodie DB, Philip JH. BJA 1995; 74:491-492.
Clinical
Viscosities of other infusates
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Infusate ViscosityWater 1.00Hespan 3.655% Albumin 1.09Haemaccel (Hoechst U.K) 1.50Dextran 40 in saline 4.01Dextran 70 in saline 3.28Dextran 40 in D5 W 4.92Propofol 1.45Thiopental 1.03Intralipid 1.36D17 W 1.36Osmolyte (Gastric) 6.57
Goodie DB, Philip JH. BJA 1995; 74:491-492.
Viscosities of other infusates
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High Flow is Nonlinear
P = R L F + R T F2
F < 3 L / hr PFR is linearF >> 3 L / hr, PFR is non-linearNonlinearity limits flow during fluid resuscitation
PFR for IV tubing systems and other fluid conduits is distinctly non-linear
Not Laminar flow ( Reynolds Number > 5,000)
Philip BK, Philip JH.Characterization of flow in intravenous infusion systems. IEEE Trans Biomed Eng. 1983; 30:702-7.
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PFR for Standard Tubing Set
0 2 4 6 8 10 12
F ml/s
100
0
200
300
400
RP = F
P = RTRLF 2+ F
nP A F=
or
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Plot of Residuals showsQuadratic is Correct
0 32 4 5 6 7 8 9 101
15
10
5
0
-5
-10
-15 Flow (mL / sec)
Analysis of residuals, Comparing 3 flow models
P = RTRLF 2+ F
nP A F=
RP = F
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Analyzing Tissue Spaces
Femoral HeadAvascular Necrosis -
Is it produced by Vascular Outflow Obstruction?
No !
Warner, Philip, Brodsky, ThornhillClin Ortho & Relat Res. 1987; 225: 128-1401987 Stinchfield Award Orthopedic Research
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Epidural SpaceWe can learn a great dealby carefully creating fluid flowand measuring pressure
Rocco AG, Philip, JH, Boas RA, Scott D. Epidural Space as A Starling Resistor and Elevation and Inflow Resistance in A Diseased Epidural Space. Reg Anesth. 1997; 22:167-177.
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Epidural SpaceExperimentFind SpaceP - V relationship, through a 17 G NeedlePinitial = negative, - 15 to - 5 mmHgAdd 0.1 mL P = 0 mmHgAdd 0.1 mL P = 10 mmHgAdd 0.1 mL P = 10 mmHgAdd 1.0 mL P = 10 mmHgAdd 3.0 mL P = 13 mmHgAdd 3.0 mL P = 16 mmHg
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Epidural Space
Time (seconds)
Annotated Automated Epidural Graphic Report
Volume =
Flow
-10
0
10
20
30
40
P (mmHg)
0 50 100 150 200 250 300
3 mL
3 mL
0.1 mL0.1 mL0.1 mL
6 mL
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Epidural Space
Time (seconds)
Plateau after 0.1 - 0.3 mL
Volume =
Flow = 360 mL / hr = 0.36 L / hr = 6 mL / min = 1 mL / 10 sec = 3 mL / 30 sec = 0.1 mL / sec
-10
0
10
20
30
40
0 50 100 150 200 250 300
3 mL
3 mL
0.1 mL0.1 mL
Plateau=
10 mmHg
0.1 mL
6 mL
P (mmHg)
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Epidural Space
Time (seconds)
Inflow Resistance = ∆ P / ∆ F during infusion
Volume =
Flow = 0.36 L / hr
-10
0
10
20
30
40
0 50 100 150 200 250 300
3 mL
3 mL
0.1 mL0.1 mL
Plateau=
10 mmHg
0.1 mL
6 mL
=Rin∆ P
∆ F
P (mmHg)
= 25 mmHg0.36 L / hr = 70 RU
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Epidural Space
Time (seconds)
Compliance = ∆ V / ∆ P
Volume =
Flow = 360 mL / hr = 0.36 L / hr = 6 mL / min = 1 mL / 10 sec= 0.1 mL / sec
-10
0
10
20
30
40
0 50 100 150 200 250 300
3 mL
3 mL
0.1 mL0.1 mL
Plateau=
10 mmHg
0.1 mL
6 mL
= 25 mmHg0.36 L / hr = 70 RU
=Rin∆ P
∆ F
C = ∆ V∆ P = 6 mL
6 mmHg= 1 mL
mmHg
P (mmHg)
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Epidural SpaceMeasure Several ParametersInflow Resistance = RinCompliance = COutflow Resistance = Rout
Rin differentiates different Clinical ConditionsRin is elevated in Spinal Stenosis and other inflammationRin is normal with herniated discC is normal in Spinal Stenosis and Disc DiseaseRout is normal in Spinal Stenosis and Disc Disease
Impact of treatment on Rin - Not studied yet
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Epidural Pumps and Dangers of Free Flow
If an epidural pump were capable of free flow from an elevated bag, would t be dangerous?
Yes> 500 mL / hour free flow into epidural spaceEpidural drug absorbed
Epidural drug volume stays at approximately 18 mLAnesthetic could be replaced at 500 mL / hrOverdose of effect, overdose of systemic drug
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There is a lot moreto learn
from the physics of fluid flow
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Thank you
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End
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Further Reading on Infusion
SciencePhilip JH. Model of the Physics andPhysiology of Fluid Administration. Journal of Clinical Monitoring.1989; 5:123-134.
SummaryPhilip JH. Intravenous Access and Delivery Principles. In: Rogers MC, Tinker JH,Covino BG, Longnecker DE.Principles and Practice of Anesthesiology.St Louis: Mosby. 1992: 1183-1196.
Thank you