Infusing Liquids Into Veins And Other Tissuesetherweb.bwh.harvard.edu/education/PHILIP/Tech_Block_04/...Infusing Liquids in Veins and Other Tissues James H. Philip, ME(E), MD, CCE

Infusing LiquidsInto Veins

And Other Tissues

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Infusing LiquidsInto Veins

And Other Tissues

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© 2004 James H Philip, all rights reserved.No part of this lecture can be used for anything but

learning without express permission

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

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

History

Clinical IV SystemsConduits - tubing and catheters

VeinsCollapsible tubes of latex

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

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

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

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

Compress a Vein

Veins

Collapse

Completely

Pressure

Compress Tubing

Pressure

Tubes

Collapse

Incompletely

Compress Tubing

Pressure

Tubes

Collapse

IncompletelyTwo

TubesRemain

Make Tubing CollapseTwo Small

Tubes

Filled withSiliconeClose

Completely

Big TubeCollapses

Completely

Latex Tubes vs. VeinsLatex Tubes (Penrose Drains)

Complex Behavior Collapse Incompletely1 big tube becomes two small tubes

VeinsSimple BehaviorCollapse Completely

VeinsCan be collapsed

Can be compressed

Cartoon depiction

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

Vein

Pvein = R FPvein

Vein

Require additional pressure for flowPvein = P0 + R F

If compressed, require opening pressurePvein = P0 = Tourniquet Pressure

Pvein

Ptourn

Pvein = R F

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

Non- Linearity

Another one Grand Rounds 2 weeks agoVaporizer with a liquid that almost boilsPhase transition or a State Transition Liquid to Gas

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

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.

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

Graphs of relationshipsbetween P and F

Pressure

Flow

Flow

Pressure

Elevated bagand Flow Measure(drop rate)

Pressure-driven

PFR

Graphs of relationshipsbetween P and F

Pressure

Flow

Flow

Pressure

Infusion Pumpand Pressure Transducer

Flow-driven

FPR

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

Flow Source - Infusion Pump

F = Fset

P(mmHg )

F ( L / hr )

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

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

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

500 100 200 300150 2500

5

10

15

20


F (m L / hr )

R = ∆ P∆ F

Resistors and Resistance

Pre

ssur

e (m

mH

g)

F ( L / hr )0.30.20.1

500 100 200 300150 2500

5

10

15

20


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

500 100 200 300150 2500

5

10

15

20


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

500 100 200 300150 250tubing(3)#16 (6)#18 (6)#20(17)

#22(34)

#24(66)

0

5

10

15

20catheters


F (mL / hr )

Catheters are Resistors

Pre

ssur

e (m

mH

g)

#Ga(R )mmHg

L/hr

500 100 200 300150 250tubing(3)#16 (6)#18 (6)#20(17)

#22(34)

#24(66)

0

5

10

15

20catheters


#Ga(R )

F (mL / hr )

Tubings are Resistors

Pre

ssur

e (m

mH

g)

mmHg

L/hr

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


F ( mL / hr )

Roller Clamps are Resistors

Pre

ssur

e (m

mH

g)

#Ga(R )mmHg

L/hr

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

Resistances in Series Add

Total Resistance = Sum of Individual Resistances

TubingCatheterRoller ClampOther DevicesPatient Vein

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

Total Resistance

Dominated by patient veinAffected by tubing and catheter

0

10

20

30

40

50

60

70

80

90

100

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)

0

10

20

30

40

50

60

70

80

90

100

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)

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

0

10

20

30

40

50

60

70

80

90

100

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)

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

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)

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)

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.

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

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

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)

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)

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

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

Alaris (IVAC) Signature Pumpmonitors Hydraulic Resistance

Alaris (IVAC) Signature Pumpmonitors Hydraulic Resistance

Present Clinical Applications

of ResistanceDevice evaluation (catheters, tubing,..)

Site AssessmentCatheter Size SelectionFluid Resuscitation OptimizationSpace Identification (epidural, axillary,..)

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

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


Site A

sses

smen

t

Pre

ssur

e (c

mH

2O)

R measured by Bag Elevationeven in the presence of a venous tourniquet


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

)

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

Choice of Catheter Size

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.

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.

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.

Viscosity Effects

Apparent Resistance is proportional to Viscosity

Goodie DB, Philip JH. Viscosities of commonly infused substances. BJA 1995; 74:491-492

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)

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

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

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

Viscosity of Various Clinical Infusates

Goodie DB, Philip JH. BJA 1995; 74:491-492.

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


Viscosities of other infusates



Clinical




Clinical





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.

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

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

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

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.

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

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

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)

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

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)

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

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

There is a lot moreto learn

from the physics of fluid flow

Thank you

End

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

Documents

Infusing Liquids Into Veins And Other Tissuesetherweb.bwh.harvard.edu/education/PHILIP/Tech_Block_04/...Infusing Liquids in Veins and Other Tissues James H. Philip, ME(E), MD, CCE