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EFFECTS OF TRANSDERMAL NITROGLYCERIN
ON A NEWLY CREATED ARTERIOVENOUS
FISTULA FOR HEMODIALYSIS
ZACHARIAH PAUL POLACHIRAKAL, GEORGE KURIAN, RAJESH R NAIR, ANIL MATHEW, SANDEEP S
Department of Nephrology, Amrita School of Medicine
Amrita Institute of Medical Sciences & Research Centre
Kochi, Kerala, India
AVF MATURATION & ROLE OF
NITROGLYCERIN
Low flow with
poor shear
stress
neointimal
hyperplasia
failure of
venous
dilatation
 Mimics the actions of endogenous nitric
oxide by releasing nitric oxide
 Acts directly on the vascular smooth muscle
 causes
 vasodilatation
 inhibit platelet aggregation
 inhibit leukocyte endothelial interactions.
AVF Maturation Cascade
Medial hypertrophy
further increased flow  increase in
pressure within the venous segment
Arterial and venous dilatation
Increase in NO, ROS and matrix
metalloproteinase
Increase in arterial and venous shear stress
Increased arterial and venous flow
Patient selection &
Doppler assessment (D0)
After 24 hours
Doppler assessment (D1)
n = 60
AVF Surgery
After 24 hours
Doppler assessment (D2)
n = 25
Arm 1
Placebo
patch
After 24 hours
Doppler assessment (D2)
n = 25
Arm 2
Nitroderm
TTS 5
 Inclusion
 Age > 20 yrs < 60 yrs.
 CKD Stage 3 – 5.
 Radiocephalic AVFs
 Exclusion
 Evidence of PVOD, CAD, stroke
or vasculitis; thrombotic segment
or thrombophlebitis
 Hypersensitivity to NTG or use of
phosphodiesterase inhibitors or
oral nitrates.
 Failed AVF ~ within 24 hr
Double blind randomized
controlled prospective trial
STUDY DESIGN & METHODOLOGY
Doppler parameters
Baseline
Mean ± SD
After 24 hours
Mean ± SD
p value
Artery diameter (cm) .2604 ± .0254 .2612 ± .0261 .161
Arterial PSV (cm/sec)
162.86 ± 23.24 175.26 ± 24.84 .001
Vein diameter (cm) .3352 ± .0466 .3380 ± .0458 .003
Venous PSV (cm/sec)
201.34 ± 38.21 220.62 ± 42.30 <.0001
Flow volume (ml/min) 1071.42 ± 317.67 1207.51 ± 393.90 <.0001
Artery diameter (cm) .2548 ± .0309 .2724 ± .0328 <.0001
Arterial PSV (cm/sec) 151.28 ± 28.00 198.16 ± 37.86 <.0001
Vein diameter (cm) .3340 ± .0552 .3560 ± .0687 <.0001
Venous PSV (cm/sec) 199.20 ± 41.04 250.12 ± 38.01
<.0001
Flow volume (ml/min) 1037.61 ± 293.03 1501.40 ± 526.92 <.0001
PLACEBOArmNITRODERMArm
R
E
S
U
L
T
S
Doppler
parameters
Placebo arm
%
Nitroderm arm
%
p value
Artery diameter 0.2 7 < .0001
Arterial PSV 9 33 < .0001
Vein diameter 1 6 .010
Venous PSV 10 28 0.006
Flow volume 12 44 .001
PERCENTAGE DIFFERENCE BETWEEN DOPPLER
INDICES BETWEEN THE TWO ARMSR
E
S
U
L
T
S
CONCLUSION
 Percentage increase in the doppler indices were 3 to 5 times
higher in study group
 Superficial location of AVF - ideally suited to local drug delivery
systems.
 Transdermal NTG  vasodilatation  increase blood flow
through the fistula  increased shear stress.
No conflict of interests or financial aids to declare.
This study was not sponsored.
Part of this study was presented at the
11th annual conference of ASDIN, Orlando, Feb 2015
9th annual conference of VAS, Barcelona, April 2015.
Ongoing trial to study the effects of tNTG in
the long term AVF maturation
Primary patency rates
Will AVF mature faster
Dosing of the intervention
ACKNOWLEDGEMENT

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EP7:Transdermal Nitroglycerin Role In AVF Maturation

  • 1. EFFECTS OF TRANSDERMAL NITROGLYCERIN ON A NEWLY CREATED ARTERIOVENOUS FISTULA FOR HEMODIALYSIS ZACHARIAH PAUL POLACHIRAKAL, GEORGE KURIAN, RAJESH R NAIR, ANIL MATHEW, SANDEEP S Department of Nephrology, Amrita School of Medicine Amrita Institute of Medical Sciences & Research Centre Kochi, Kerala, India
  • 2. AVF MATURATION & ROLE OF NITROGLYCERIN Low flow with poor shear stress neointimal hyperplasia failure of venous dilatation  Mimics the actions of endogenous nitric oxide by releasing nitric oxide  Acts directly on the vascular smooth muscle  causes  vasodilatation  inhibit platelet aggregation  inhibit leukocyte endothelial interactions. AVF Maturation Cascade Medial hypertrophy further increased flow  increase in pressure within the venous segment Arterial and venous dilatation Increase in NO, ROS and matrix metalloproteinase Increase in arterial and venous shear stress Increased arterial and venous flow
  • 3. Patient selection & Doppler assessment (D0) After 24 hours Doppler assessment (D1) n = 60 AVF Surgery After 24 hours Doppler assessment (D2) n = 25 Arm 1 Placebo patch After 24 hours Doppler assessment (D2) n = 25 Arm 2 Nitroderm TTS 5  Inclusion  Age > 20 yrs < 60 yrs.  CKD Stage 3 – 5.  Radiocephalic AVFs  Exclusion  Evidence of PVOD, CAD, stroke or vasculitis; thrombotic segment or thrombophlebitis  Hypersensitivity to NTG or use of phosphodiesterase inhibitors or oral nitrates.  Failed AVF ~ within 24 hr Double blind randomized controlled prospective trial STUDY DESIGN & METHODOLOGY
  • 4. Doppler parameters Baseline Mean ± SD After 24 hours Mean ± SD p value Artery diameter (cm) .2604 ± .0254 .2612 ± .0261 .161 Arterial PSV (cm/sec) 162.86 ± 23.24 175.26 ± 24.84 .001 Vein diameter (cm) .3352 ± .0466 .3380 ± .0458 .003 Venous PSV (cm/sec) 201.34 ± 38.21 220.62 ± 42.30 <.0001 Flow volume (ml/min) 1071.42 ± 317.67 1207.51 ± 393.90 <.0001 Artery diameter (cm) .2548 ± .0309 .2724 ± .0328 <.0001 Arterial PSV (cm/sec) 151.28 ± 28.00 198.16 ± 37.86 <.0001 Vein diameter (cm) .3340 ± .0552 .3560 ± .0687 <.0001 Venous PSV (cm/sec) 199.20 ± 41.04 250.12 ± 38.01 <.0001 Flow volume (ml/min) 1037.61 ± 293.03 1501.40 ± 526.92 <.0001 PLACEBOArmNITRODERMArm R E S U L T S
  • 5. Doppler parameters Placebo arm % Nitroderm arm % p value Artery diameter 0.2 7 < .0001 Arterial PSV 9 33 < .0001 Vein diameter 1 6 .010 Venous PSV 10 28 0.006 Flow volume 12 44 .001 PERCENTAGE DIFFERENCE BETWEEN DOPPLER INDICES BETWEEN THE TWO ARMSR E S U L T S
  • 6. CONCLUSION  Percentage increase in the doppler indices were 3 to 5 times higher in study group  Superficial location of AVF - ideally suited to local drug delivery systems.  Transdermal NTG  vasodilatation  increase blood flow through the fistula  increased shear stress. No conflict of interests or financial aids to declare. This study was not sponsored. Part of this study was presented at the 11th annual conference of ASDIN, Orlando, Feb 2015 9th annual conference of VAS, Barcelona, April 2015. Ongoing trial to study the effects of tNTG in the long term AVF maturation Primary patency rates Will AVF mature faster Dosing of the intervention ACKNOWLEDGEMENT

Editor's Notes

  1. AVF – THE LIFELINE Well functioning AVF -A CHALLENGE Blood flow, vasodilatation and endothelial function Development of a successful AVF Neointimal nature Flow mediated dilatation - important role Modulate these factors  improved AVF function