This document discusses flap physiology and references related to flap surgery. It covers topics such as blood supply to skin and flaps, vascular regulation of cutaneous blood flow, haemodynamic alterations during flap elevation, and factors that influence flap perfusion and viability. Key concepts addressed include the angiosome concept of vascular territories, differences between random and axial flaps, and local vs. systemic control of microcirculation in skin and muscle.

1. Flap physiology

2. References
• Mathes. Plastic surgery Vol 1
• Janis J. Essentials of Plastic Surgery 2007
• Peter C. Neligan. Plastic surgery third edition, volume one, 2013. 573-588
• Grabb & Smith’s Plastic surgery 6th Ed 2007
• Kayser M. Surgical Flaps. Selected Readings in Plastic Surgery
• Carroll WR, Esclamado RM. Ischemia/reperfusion injury in microvascular surgery. Head
Neck 22:700,2000
• Siemionow M, Arslan E. Ischaemia/reperfusion injury: a review in relation to free tissue
transfers. Microsurgery. 2004;24(6):468-75
• Nguyen et al. Outcomes of flap salvage with medicinal leech therapy. Microsurgery. 2012
Jul; 32(5): 351-7
• Salgado CJ, Moran SL, Mardini S. Flap monitoring and patient management. Plast
Reonstr Surg. 2009 Dec;124(6 suppl): e295-302

3. References
• Janis J, Kwon R The new reconstructive ladder: modifications to the traditional model.
Plast. Reconstr. Surg. 127 (suppl.): 2055,2011
• Davis et al. The strength of microvascular anastomoses – an experimental evaluation in
rats. J Microsurg. 1982 Spring; 3(3):156-61
• Chiu et al. Free flap monitoring using skin temperature strip indicators – adjunct to
clinical examination. PRS 2008 122(5) pg 144e.
• Lin et al. Tissue oximetry monitoring in microsurgical breast reconstruction decreases
flap loss and improves rate of flap salvage. PRS 2011 127(3), 1080
• Giunta et al. Prediction of flap necrosis with laser induced indocyanine green
fluorescence in rat model. BJPS 2005 58, 695
• Askari et al. Anti coagulation therapy in microsurgery – A review. J hand surg 2006;31A
836-846
• Machens et al. Flap perfusion after free musculocutaneous tissue transfer: the impact
of postoperative complications. Plast Reconstr Surg. 2000 June; 105(7):2395-9

4. Topic outlines
1. Introduction
2. Regulation of flap blood flow
3. Haemodynamic alterations on flap elevation
4. Metabolic changes in flap elevation
5. Ischaemic reperfusion injury
6. Ischaemic preconditioning & delay phenomenon
7. Timing of flap division
8. Flap failure or necrosis
9. Therapeutic interventions to improve flap survival
10. Flap monitoring

5. What is a flap?
• It is the essence of plastic surgery
• Distinguished from graft in that it has an intrinsic vascular
blood supply that is responsible for a flap viability
o Graft relies on diffusion until its vascularity becomes re-
established
• Blood supply to flaps involves a continuous 3D network of
vessels in all tissue layers following the angiosome concept
– An angiosome: a block of composite tissue supplied by all the
perforators of a source artery

6. Vascular supply of flaps
• Include both macrocirculation and microcirculation components
• Both are subject to intrinsic and extrinsic factors that influence
perfusions and thus viability
Macrocirculation:
• Anatomy of which is used to define and design a flap
• Major arterial inflow and venous outflow of a flap constitutes the
foundation of the microcirculatory function
Microcirculation:
• Consist of arterioles, capillaries, venules and arteriovenous
anostomoses
• Provides nutrition and oxygen
• Carries away carbon dioxide and waste products
• Therefore these form the basis of cellular metabolism throughout the
flap
• It is also where most of the control of the perfusion occurs

7. Blood supply to skin

8. Vascular structure of skin: Work of Manchot, Salmon
and Taylor
Manchot
• Hamburg, 1889
• His work entitled ‘The Cuteneous Arteries of Human Body’ was published
in English in 1983
• Describes 40 cutaneous vascular territories and assigned them to their
underlying source vessels
• Used ink injection studies on cadavers, WITHOUT the use of X-ray
• His work excluded the head, neck, hands and feet
• Limited to the cutaneous vasculature
• Only a medical student, age 23, completing his thesis within 6 mos
Salmon
• French anatomist, 1936
• Describes 80 cutaneous vascular territories, each has its own
source artery
• Uses radiographic lead oxide injection studies

9. 50 studies every plastic surgeon needs to know. CRC Press, 2015.

10. Taylor and Palmer (1987)
Proposed TWO theories of blood supply to skin
1. Angiosome concept
2. Direct or indirect route

11. Angiosome
• Angiosome derives from the Greek word Angeion, meaning vessel, and
somite , meaning segment or sector of body.
• Angiosome : A three-dimensional block of composite tissue, including
skin and its underlying deep tissue supplied by a single source of artery
and its branches
• Proposed 40 angiosomes
• Each angiosome is linked to its neighbour in each tissue by
predominantly reduced calibre vessels called choke vessels, or similar
calibre vessels called true anastomoses

12. (Chapter 8. Handbook of Plastic Surgery 2014)
intermuscular or intramuscular connective tissue to pierce the deep fascia. After
emerging from the deep fascia, the cutaneous vessels follow the
Figure 3 Schematic representation of
choke anastomoses (A) and true
anastomoses (B) between adjacent
vascular territories. (From Taylor GI;
Minabe T: The angiosomes of the
mammals and other vertebrates. Plast.
Reconstr. Surg. 89:181, 1992.)

13. Principles of Flap, SRPS Volume 10, Number 1 (2004)

14. Eg.: Angiosome of pedicled TRAM flap

15. Blood supply to the skin
1. Primary:
• Direct cutaneous arteries
• Varies in calibres, number and density in different region of the
body
2. Indirect vessels:
• Reinforce primary supply
• Terminal branches of arteries supplying the deep tissue

16. • One of the primary functions of skin is thermoregulation
o Accomplished through regulation of skin blood flow
o ↑ skin blood flow = heat dissipation
o ↓ skin blood flow = heat conserved
• Primary regulation of skin blood flow is at arteriolar level
o Sympathetic tone regulates flow through
1. Precapillary sphincters
2. Arterioles
3. Arteriovenous anastomoses
• Normal blood flow to skin is approximately 20ml per 100g of
tissues
o Higher in muscles ( due to higher demand for oxygen and
metabolites )

17. • Effective microcirculatory perfusion is dependent on its
proximity to the nearest nutrient vessel.
o Flaps that are based on an axial nutrient vascular system is
more reliable than random flaps
• Random flaps are not based on dominant nutrient vascular
system, but instead are supplied by flow through subdermal or
subfascial plexus
• Much less reliable than axial flaps
• Their length is limited to a short distance from the pedicle origin
• Therefore, the single most important factor in classifying flaps
is whether they are axial or random in nature

18. Random flap Vs Axial flap

19. Regulation of cutaneous blood flow
• Cutaneous flaps are regulated at the level of the
microcirculation
o This is where thermoregulation of blood flow occurs
• Primary regulator of blood flow in arteriolar network is
controlled by systemic and local mechanism
• Systemic control
• Neural regulation
• Humoral regulation
• Local control
• Metabolic factors
• Physical factors

21. Systemic control
Neural regulation
Sympathetic adrenergic fibres maintain basal tone of vascular smooth
muscle at the arteriovenous anastomoses,
arterioles, and arteries
Alpha adrenergic receptors Vasoconstriction
Beta-adrenergic receptors Vasodilation
Cholinergic fibres Bradykinin release  Vasodilation
Humoral regulation
Epinephrine, Norepinephrine, Serotonin,
Thromboxane A2, Prostaglandin F2
Vasoconstriction
Bradykinin, Histamine, Prostaglandin E1 Vasodilation

22. Local control (autoregulation)
• Local regulation are mediated by metabolic and physical factors.
• Important especially in those with high metabolic rate e.g skeletal
muscle
• Metabolic factors
– Act primarily as vasodilators, and include hypercapnia, hypoxia,
acidosis, and hyperkalaemia
• Physical factors
– Local hypothermia has a direct effect on vascular smooth muscle to
cause vasoconstriction
 Local hyperthermia has opposite effect
– Myogenic reflex – triggers vasoconstriction in response to distension
of isolated cutaneous vessels, thereby maintaining capillary flow at a
constant level independent of arterial pressure
– Increased blood viscosity (Hct > 45%) may also decrease flow

23. Rheologic factors
• Rheology of blood in the microcirculation is determined by the cell
concentration, plasma viscosity, red cell aggregation and
deformability as well as the vessel characteristics
• Flow in small vessel can be approximated by above formula
which follows Poiseuille’s Law.
• Flow is proportional to the fourth power of radius
• Small decrease in vessel lumen results in big decrease in flow
 Decrease in intraluminal pressure (hypovolaemia, hypotension)
 Increase in extravascular pressure (oedema, haematoma)

24. Other considerations
Same concept of cutaneous blood flow can be applied to muscle but with the
following differences:
1. Arteriovenous shunts are believed to be absent in muscle
2. Muscle has a much higher capillary density than skin
3. Metabolic demand of muscle is far greater than that of skin, thus
autoregulation plays a more important role
4. Epinephrine causes vasodilation, in direct contrast to vasoconstriction
seen in skin
5. Temperature has less effect on blood flow
6. Myogenic tone is very important in regulating blood flow in muscle
• Cutaneous blood flow predominantly rely on sympathetic vasoconstrictors

26. Haemodynamics of flap transfer
• The elevation of skin flap produces profound changes which
drastically disrupts the finely balanced equilibrium that
regulates blood flow to the tissue
• Immediate loss of sympathetic innervation that results in
spontaneous discharge of vasoconstricting neurotransmitters
• Combined with drop in perfusion pressure from physical
removal of inflow vessels, the result is that the peripheral
portions of the flap become acutely ischaemic

27. Haemodynamics of flap transfer
Hoopes’ circulatory events in a pedicled flap after its blood
supply is partially interrupted during elevation and transfer
0-24 hours:
• Reduction in arterial blood supply
• Progressively decreasing circulatory efficiency for first 6 hours
• Plateau at 6-12 hours
• Increase in circulatory efficiency beginning at 12 hours
• Marked congestion and oedema during the initial 24 hours
• Marked dilatation of arterioles and capillaries

28. Hoopes’ circulatory events in a pedicled flap during elevation and
transfer
1-3 days:
• Improvement in pulse amplitude
• Little or no improvement in circulation during the initial 48 hours
• Increase in number and calibre of longitudinal anastomoses
• Increase in the number of small vessels in the pedicle
3-7 days:
• Progressive increase in circulatory efficiency until it reaches a
plateau at about day 7
• Vascular anastomoses between flap and recipient bed present at
day 2-3, becomes functionally significant at day 5-7
• Increase in size and diameter of functioning vessels
• Reorientation of vessels along the long axis of the flap

29. Hoopes’ circulatory events in a pedicled flap during elevation and
transfer
1 week:
• Circulatory function well established between flap and recipient bed
• Pulsatile blood flow approaches preoperative levels
7-14 days:
• No further significant increase in vascularization
• Arterial pattern becomes normal
2 weeks:
• Progressive regression of the vascular system
• Continuous maturation of anastomoses between pedicled flap and
recipient site

30. Hoopes’ circulatory events in a pedicled flap during elevation
and transfer
3 weeks:
• Vascular pattern approximates preoperative state
• Flap achieves 90% of its final circulation
• Fully developed vascular connections between pedicle and
recipient site
4 weeks:
• All vessels decreased in diameter, few remaining newly formed
vessels

31. • Ultimate outcome of flap following flap elevation is determined
by haemodynamic, anatomic and metabolic changes
• Palmer, Nathanson, and Kerrigan carried out studies using
labelled microspheres to study the haemodynamic changes
o Showed that although flow at the base of a pedicle is preserved
after elevation, flow at the tip of the flap often drops to < 20% of
normal within first 6-12 hours
o Flow gradually returns to approximately 75% of normal within 1-2
weeks, and to 100% by 3-4 weeks
• As gradual returning of flow to the ischaemic portion of flap
occurs by longitudinal flow from pedicle, additional flow is also
returning by inosculation, and neovascularization from the
bed

32. • Musculoutaneous flaps take on the perfusion benefits of underlying
axial muscle flap
• Gottrup et al, showed that they have an early and continuous increase
in blood flow after elevation
• Whereas random skin flaps have an early decrease but develop a
subsequent lasting increase in flow
• Tissue oxygen tension higher in musculocutaneous flaps up to 6 days
after elevation, and are higher in proximal than distal portions in each
flap type
• This difference is greater in random-pattern flap than in axial muscle or
musculocutaneous flap
• Differences in patterns of oxygen delivery to random vs
musculocutaneous flaps, may explain the greater reliability of
musculocutaneous flaps when they are used in the presence of
infection
• Provides better bacterial killing function in the setting of an infection

33. • Banbury et al described muscle flaps’ triphasic
microcirculatory response to sympathectomy & denervation.
• The genitofemoral nerve of 30 rats was divided and the
proximal vessels were stripped of their adventitia. The
muscle was not elevated.
• Red blood cell velocity increased transiently, immediately after
denervation
• Main arterioles dilated at 24 hours
• Capillary perfusion increased at 2 weeks
• The microvessels had hyperactive responses to all vasoactive
agents 2 weeks after denervation
1. Initial acute hyperadrenergic phase
2. Non adrenergic phase (with significant vasodilatation)
3. Sensitized phase (Increased capillary perfusion &
hyperresponsiveness vasoactive substances)

34. Metabolic changes following flap
elevation
1. Ischaemic tissue undergoes anaerobic metabolism
– Rapid depletion levels of oxygen, glucose and ATP
– Concomitant increase of CO2 and lactic acid
2. Prostacyclin & thromboxane levels are elevated
3. Glucose & Glycogen consumption increased in ischaemic but
viable portions of the flap, in proportion with the degree of
ischaemia
4. Glucose consumption peaks around D3, and returns to
normal by D7

35. 5. Increased production of toxic superoxide radicals (a/w
anaerobic metabolism)
– Causes direct cytotoxic effects
– Acts as trigger for local acute inflammation, adherence and
accumulation of leukocytes, and subsequent endothelial
injury
– Subsequent cellular events leads to microvascular shutdown
6. Levels of superoxide dismutase decreased in distal
portions of acute flaps as the enzyme is consumed in
converting superoxide to oxygen in a tissue-protective
mechanism
Metabolic changes following flap
elevation

36. Reperfusion injury

37. Reperfusion injury
Ischaemic period
• Cell energy level falls, disrupting ion gradients and
allowing calcium to enter cytoplasm
• Calcium activates a cytosolic enzyme that transforms
xanthine dehydrogenase to xanthine oxidase which
reduces molecular oxygen into oxygen free radicals

38. • During reoxygenation after ischaemia, xanthine dehydrogenase
is converted to xanthine oxidase
– Catalyzes the conversion of Hypoxanthine + O2  Xanthine
– With production of superoxide anion as byproduct
– Superoxide anion then lead to formation of other oxygen radical
species  direct cellular injury
Reperfusion injury

40. Pathogenesis of ischaemic reperfusion injury:
• When O2 is reintroduced, superoxide anion, hydrogen
peroxide and hydroxyl radical are produced. These
metabolites causes injury via:
1. Direct reaction of superoxide radical with endothelial
membrane
– Causes lipid peroxidation, disruption of membrane proteins,
increased cell permeability
– Consequently cytoplasmic swelling & dysfunction
2. Chemotactic property of O2 metabolites, primarily superoxide
anion
– Causes neutrophil migration into the reperfused area, with the
neutrophils actually causing tissue destruction

41. Pathogenesis of ischaemic reperfusion injury:
3. Arachidonic acid metabolism pathways
• Activated neutrophils produce leukotrienes and perpetuate
inflammatory reaction
• The activation of lipoxygenase that yields leukotriene B4 (a potent
chemoattractant) further induce superoxide anion generation and
degranulation in neutrophils, leading to further generation of free
radicals & neutrophils recruitment
• Similarly, cyclooxygenase, in the setting of ischaemia, results in
the generation of thromboxane & prostaglandins
– Thromboxane A2 is a potent vasoconstrictor & induces platelet
aggregation
– Prostacyclin (PGI2) is a potent vasodilator, inhibitor of platelet
aggregation & increase capillary permeability
• LTB4, TXA2 & PGs – all important in microvascular & inflammatory
derangements

42. • Free radicals also play an important role in hematoma-
related flap necrosis
– Hemoglobin and iron catalyse the chemical reactions that lead
to the production of highly destructive free radicals, in
particular the hydroxyl radical

43. • The rapid
intravascular
accumulation of
neutrophils can lead
to progressively
decreased perfusion
and may represent
the “no-reflow”
phenomenon with
ischaemia and
reperfusion

44. The role of neutrophils in ischaemic
reperfusion injury
Activated PMNs may cause injury through:
– Direct endothelial injury, resulting in loss of
vascular integrity, oedema, haemorrhage and
thrombosis
– Microvascular occlusion, and further
ischaemia resulting from adherence and
accumulation of aggregates of PMNs within
the vessel lumen

45. Regulation of neutrophil adhesion
Two major adhesion
molecules:
1. The selectins and their
carbohydrate
counterstructures
2. The leukocyte integrins
and their ligands on
endothelial cells that
are members of the
immunoglobin (Ig)
superfamily

46. • The selectin receptors are lectin-containing proteins that
recognize specific carbohydrate counsterstructures, expressed
on glycoproteins.
– Responsible for the initial transient adhesion of neutrophils that
occurs at sites of inflammation, manifested as “rolling”
• Once slowed by selectin-carbohydrate interactions, local
inflammatory stimuli subsequently activate the neutrophils to
produce firm adhesion through the integrin-Immunoglobulin-
like-ligand interaction
– Mediates the steps of firm adhesion of neutrophils to endothelium
at sites of inflammation, diapedesis & emigration

47. • Many inflammatory mediators & vasoactive substances have
been implicated in recruitment, adhesion, migration, &
activation of neutrophils to further inflict tissue injury in
ischaemic reperfusion phenomenon
o Thrombin
o Histamine
o Oxidants
o Interleukin-1
o TNF-
o Platelet activating factor
o Chemotactic peptides (eg C5a)
o Chemokines (eg Interleukin-8)

49. Ischaemic preconditioning & delay
phenomenon (non-lethal ischaemia)
• Ischaemic preconditioning is a process whereby tissue is
subjected to a brief period of non lethal ischaemia
• This process confers the tissue a resistance to damage by
subsequent prolonged ischaemic events
• This phenomenon was first described by Murry et al in a
model of myocardial ischaemia-reperfusion, in which it was
shown to reduce infarct size in rat myocardium

50. • Surgically, flap survival can be extended by the strategic
division of vascular pedicles at various time intervals along
the length of the proposed flap – the “flap delay” procedure
• Delay is the surgical interruption of a portion of the
blood supply of a flap at a preliminary stage before
transfer

51. Purpose of flap delay procedure:
• To increase the surviving dimension (length)
of a skin flap
• To improve the circulation of a flap
• Diminish the insult of transfer
Arteriogram of control (left) and delayed (right) rectus abdominis muscle of a dog 7 days
post operatively.
Note the dilated choke vessels in the delayed flap by ligation of the deep inferior epigastric
artery (arrow)

52. • Theories of flap delay concept:
– Conditions tissue to ischaemia, allowing it to survive on less nutrient
blood flow than normally needed
– Improves or increases vascularity through
o Dilation of choke vessels connecting adjacent vascular territories
o Reorientation of vessels within the flap to a more longitudinal pattern
o Angiogenesis & vasculogenesis
• Five mechanisms of delay phenomenon (according to Hoopes):
1. Sympathectomy
2. Acclimatization to hypoxia
3. Vascular reorganization
4. Reactive hyperemia
5. Non specific inflammatory reaction (producing vasodilation)
• Maximum survival of delayed flap achieved at 1 week & minimum
effective time is 2-3 days

54. Anatomic changes in flap delay
• Sympathectomy causes depletion of cathecholamines from
the initial procedure itself
– Begins after incision and ending by 30 hours
– Hence, enhanced vascularity from less vasoconstriction due to
lack of cathecolamines
• Gradual hypertrophy of blood vessels & acclimatization to
hypoxia as a result of ischaemic tissue conditioning from
exposure to lower O2 tension or poor circulation
– Vessel enlargement is permanent & irreversible involving
o Multiplication (hyperplasia)
o Elongation
o Hypertrophy of red cells in each layer of the vessel wall
– Maximum effect between 48-72 hours after operation

55. • Vascular reorganization
– Longitudinal reorientation of small vessels parallel to the long
axis of pedicles at 1-7 days post delay
• Reactive hyperemia
– Due to increase resistance to venous outflow, and increase in
size & number of subdermal arterial & dermovenous plexuses
– These vessels are toneless, dilated and unable to respond to
local changes
• Ingrowth of new vessels (neovascularization)
– 4 to 5 days post operatively
– Vasodilation & angiogenesis until about day 14

56. Hemodynamic changes in flap delay
• Overall blood flow increase reached 75 - 90% of normal by the second
week
o Vasodilation hypothesis – relaxation in precapillary arterioles of
delayed flaps as a result of
– Sympathectomy
– Tissue ischaemia with local arterial dilation
– Inflammation producing vasodilation
– Formation of new collateral vessels or dilation of pre-existing channels
• Significantly higher capillary blood flow in delayed random flap
– Increase flow detectable within 2 days of surgical delay
– Increased 100% by D4
– Remained plateau until D14
• AV shunts do not have significant role in the pathogenesis of distal skin
flap necrosis
– Tissue ischaemia due to vasoconstriction of small random arteries that
supply blood to arterioles in AV shunts

57. Metabolic changes in flap delay
• Increase glucose consumption & lactate production, with
concomitant depletion of glycogen
• Inadequate tissue oxygenation leads to a change from
aerobic to anaerobic metabolism, releasing higher levels of
superoxide radicals
• Metabolic derangements affect physical properties of blood
such as viscosity and clotting

58. • However, a critical minimal level of tissue glucose is
necessary to accommodate metabolic adaptation in the
ischaemic tissue
– Glycolytic enzyme level highest in the first 3 days, supporting
the theory that delay acclimatizes tissue to hypoxia
– Metabolic changes reversible for up to 4 hours
– Ischaemic periods of 12 hours and longer resulted in
complete loss of energy reserves

59. In summary:
• Initial primary event is dilation of existing vessels within
the flap, no ingrowth of new vessels
– Initial period of vasoconstriction resolved within 3 hours post
operatively
• Active and progressive dilation of choke vessels is most
dramatic between 48-72 hours
• Choke vessels dilation is permanent & irreversible
– Hyperplasia & hypertrophy of the cells in all layers of the
choke artery wall
• In clinical setting, the traditional delay period is 2-3 weeks

60. Timing of flap division
• Hoffmeister concluded that flap transfer is best done 2-4
weeks after delay
• Arterial connections between the transferred flap and its bed
begins at 4 to 5 days and venous drainage several days
earlier
• Although flap division can be performed safely as early as
day 3 in many animal studies, clinically this interval must be
lengthened according to
- Regional anatomic differences
- On-the-spot assessment of flap viability and “vigor”
- Size and characteristics of the recipient site
- Presence or absence of infection
- Haematoma

61. • Hauser et al proposed that the traditional mean of 3 weeks
for division of an inset flap is probably acceptable in 85% of
patients, but is premature in some and excessively long in
most
• On the basis of published reports as well as the cumulative
anecdotal experience of many surgeons, it may be concluded
that most flaps can safely be divided between 10 days and 3
weeks
• For free flap, Berger and Machens showed that flap perfusion
remained autonomous on its vascular pedicle even after 10
years of surgery

62. Flap failure or necrosis
• Multifactorial
1. Composition of the flap
2. Arterial or venous insufficiency
3. Presence of global ischaemia

63. 1. Composition of the flap
• Inherent blood flow
o Proximal pedicled flap – reduced blood flow as a result of
sympathectomy, cathecolamine release, & local response to injury
o Distal portion - local ischaemia (even in maximal vasodilation) due to
inadequate perfusion pressure from the proximal portion
• Tolerance to ischaemia
o Factors affecting ischaemic tolerance
– Ischaemia time
– Energy & metabolic requirements
– Temperature: cold vs warm
– Tissue composition
 Gut  muscle  skin  Bone  Cartilage
 Decreasing metabolic demand

64. • Adipocutaneous flaps can tolerate ischaemia better than
musculocutaneous flaps
• Ischaemia time of up to 4 hours for a perforator flap may be
well tolerated
• Musculocutaneous flaps, on the other hand, do not tolerate
prolonged ischaemia time because of the metabolic requirement
of the muscle
• In general, 2-3 hours of ischaemia is the maximum time
tolerated

65. Composition Skin flap Muscle flap
Inherent blood flow Less blood flow More blood flow
Response to ischaemia Marked decrease in flow
rate
Early hyperemic phase
during reperfusion
- Maintain significant
blood flow to all region
- Including area that is
destined for necrosis
Tolerance to ischaemia - Lower metabolic
requirement
- More tolerant to
ischaemia
- Higher metabolic
demand
- Less tolerant to
ischaemia

66. 2. Arterial or venous insufficiency
• Sufficient reduction in venous outflow can produce flap
necrosis despite adequate arterial inflow
– In free tissue transfers, venous occlusion is more common than
arterial occlusion
– In most pedicle flaps, however, the two are closely linked and
any venous insufficiency in the face of impaired arterial inflow will
lead to significant tissue necrosis
• Venous insufficiency causes more damage than equivalent
arterial insufficiency
• Hjortdal et al & Gurlek et al found significant stasis,
hemoconcentration, and increased viscosity were associated
with venous ischaemia

67. 3. Presence of global ischaemia (the entire flap is ischaemic) due
to
• Flap design too large for its intrinsic blood supply
• Arterial thrombosis
– Platelet aggregation is the underlying cause
• Venous thrombosis
– Primarily the result of fibrin clotting
• In random & axial pedicle flap
– Thrombosis usually secondary to low-flow state in microcirculation
level
o Improper flap design
o Ischaemia reperfusion injury
o Systemic causes (eg hypotension, smoking, sepsis,
vasoconstrictors)
o Local physical compression of flap (eg Improper inset, kinking,
hematoma)

68. • In free flaps
– Thrombosis at site of microvascular anastomosis
o Due to poor technique (allowing prothrombotic adventitia or
media to be exposed to the luminal blood flow, with subsequent
platelet & fibrin deposition
• Ischaemic changes are reversible up to 4-8 hours of
ischaemia
• Damage irreversible after 12 hours of ischaemia at which
point, it is not possible to re-establish inflow
– No reflow phenomenon (precedes flap death)

69. Therapeutic interventions to
improve flap survival
• No consensus exists on the use of anticoagulation therapy after
microsurgery
• Many surgeons have their own particular protocols for
perioperative anticoagulation that has been shaped by personal
trials and errors
1. Physical factors & leeches therapy
2. Pharmacological factors
3. Increase tolerance to ischaemia
4. Modulating proinflammatory mechanism

70. Physical factors
Factors that have experimentally demonstrated a survival
advantage include:
• Maintenance of a moist environment along flap edges
o Minimize desiccation of ischaemic tissue
• Keep flap warm
o Reduce vasoconstriction & decrease blood viscosity
• Ischaemic preconditioning
o Causes alterations in blood flow, decreased tissue metabolism,
decreased level of oxygen-derived-free radicals
o Release of endothelium-derived relaxing factors which may cause
vasodilation and improved distal blood flow

71. Physical factors
• Hyperbaric oxygen therapy
o Given as soon as possible after surgery in rat model improves
skin flap viability
o Due to increased superoxide dismutase activity & reduced
xanthine oxidase activity, especially when coupled with
prolonged cold ischaemia

72. Physical factors
• Leeches (Hirudo Medicinalis)
o Provides relief of venous congestion after free tissue transfers
and replantations
o Saliva contains
– Hirudin : a naturally occurring anticoagulant that inhibits thrombin
& prevent the conversion of fibrinogen to fibrin
– Hyaluronidase: facilitates spread of the hirudin within the tissues
– Vasodilator histamine: Contributes to prolonged bleeding (up to 48
hours)
– Mechanical effect by creating physical channels through which
venous drainage can occur

73. Physical factors
• Leeches (Hirudo Medicinalis) cont.
o Main indication is for venous congestion
– Outflow insufficient
– Venous channels either absent or unsuitable for anastomosis
o Most significant risk of leeches are
– Bacterial infection from the G-ve rod Aeromonas Hydrophilia
– Anaphylaxis
– Excessive bleeding
– Scarring if infected
o Prophylaxis with ciprofloxacin or an aminoglycoside, or a third-
generation cephalosporin sufficient
o Caution when treating immunocompromised patients

74. Pharmacologic factors
• Anticoagulants
• Receptor & axon blocker
• Direct smooth muscle relaxants
• Rheologic agents
• Anti-inflammatory agents

75. Anticoagulants:
1. Dextran
• A polysaccharide synthesized by bacteria from sucrose,
originally designed as a volume expander
• Has been shown to improve short-term microcirculatory
patency
• Mechanism of action:
o Decrease in platelet adhesiveness & procoagulant activity
o Inhibition of platelet aggregation
o Increases bleeding time
o Decrease in blood viscosity
• Usually administered as a continuous IV infusion during the
flap procedure and continuing for several days post operatively
– 500 ml/day for 3-5 days

76. Anticoagulants:
1. Dextran (cont)
• Associated with significant systemic morbidity
o Anaphylaxis
o Pulmonary oedema
o Cardiac complications
o ARDS
o Renal failure
• Therefore, a small test dose is usually administered before
infusion
• Routine use in free tissue transfer is discouraged

77. 2. Low molecular weight heparin (LMWH)
• Acts in conjunction with antithrombin III to inhibit thrombosis by
inactivation of factor X
• More effective at preventing venous thrombosis than arterial
thrombosis
• Improves microcirculatory perfusion & anostomotic patency while
minimizing haemorrhage
3. Heparin
• Act by binding to antithrombin III, which then inactivates thrombin,
factor Xa and other proteases
• Used both systemically and as a topical irrigant at the time of
anastomosis
• Flap survival improvement only when administered continuously but
clinically significant risk of hematoma formation
• Systemic heparin usually reserved for microvascular applications
when intraoperative thrombosis occurs and require mechanical
clearing
Anticoagulants:

78. 3. Heparin (cont)
• Topical irrigation with heparinized saline is a widely used technique
in microsurgery in concentration of 100 units/mL
• Beneficial effect attributed to platelet disaggregation & maintenance
of vascular patency
• A dose related increase in flap patency – target a 2 fold increase in
APTT for 3-7 days
4. Thrombolytic agents
• Stimulates the conversion of plasminogen to plasmin, which acts to
cleave fibrin within a thrombus
• Have been effective in salvaging flaps after microvascular
thrombosis
• First generation agents
o Streptokinase, urokinase
• Second generation agents
o Tissue plasminogen activator (t-PA)
o Acylated plasminogen-streptokinase activator complex (APSAC)
Anticoagulants:

79. Receptor & axon blocker:
• Conflicting evidence in their benefits
1. Anti adrenergic drugs
• Reserpine and guanethidine deplete norepinephrine stores in nerves and
lessen the effects of alpha and beta agonists
• Propanolol opposes beta-mediated metabolic stimulation
• Phentolamine causes vasoconstriction mainly by blocking alpha-receptors
2. Topical nitroglycerin
• A potent vasodilator
• Greater effect on the venous circulation than on arterial vessels
3. Amrinone
• Selective phosphodiesterase III inhibitor
• Enhances microcirulatory blood flow due to its
– Positive inotropic properties
– Vasodilating properties

80. Direct smooth muscle relaxants:
1. Calcium channel blockers
• Diltiazem, verapamil, nifedipine
• Act on the vascular smooth muscles to cause vasodilation
• Improves circulation in the flap
• Diltiazem also stimulates the release of prostacyclin (PGI2), a
potent vasodilator and anti-platelet aggregator from the
vascular endothelial cells
2. Dimethyl sulfoxide (DMSO)
• Increases flap viability by
o Vasodilation
o Reduction of platelet aggregation
o Reduction of free radical scavenging

81. Direct smooth muscle relaxants:
3. Buflomedil
• A vasoactive drug
• Used clinically to treat claudication or symptoms of peripheral
arterial disease
• Protects flaps of poor design, ischaemic flaps, and flaps
suffering from reperfusion injury
• Mechanism of action:
– Inhibitory effect on platelet aggregation
– Improves the deformation capacity of red blood cells with
abnormal flowability
4. Hydralazine
• Affects arteriolar smooth muscle by increasing intracellular
cAMP, which in turn causes relaxation and reduces peripheral
resistance

82. Rheologic agents:
1. Fluorocarbons
• Lowers the viscosity of blood
• Improves microcirculation & oxygen carrying capacity of blood
2. Pentoxifylline
• Hemorrheologic agent
• Improves the deformability of red blood cells, therefore improving
its blood flow characteristics
• Decreases fibrinogen levels
– Decreases blood viscosity

83. Anti inflammatory agents:
1. Steroids
• Prednisolone & dexamethasone – controversial
• Thought to act as vasodilator and membrane stabilizer
• Also confers nonspecific anti-inflammatory effect – similar to
anti-neutrophil strategies
• Systemic steroid administration reduces flap oedema, but the
risk of infection may outweigh its perceived benefit
2. Aspirin (ASA)
• Acetylates enzyme cocylooxygenase (COX), thereby
decreasing the synthesis of Thomboxane A2 (TxA2 ), a potent
vasoconstrictor in platelets and Prostacyclin (PGI2), a potent
vasodilator in vessel walls

84. Anti inflammatory agents:
2. Aspirin (ASA) (cont)
• At low doses, the effect of aspirin is selective
– Only inhibits the cyclooxygenase system in platelets
• Experimentally, preoperative aspirin decreases thrombus
formation at venous anastomoses and improves capillary
perfusion in the microcirculation
• Carrol et al, demonstrate increased early anostomotic patency
in their study, but there’s no difference from controls after 24
hours to 1 week
• No empiric evidence in the literature for using aspirin
postoperatively

87. • In summary, there are many promising potential therapies
currently bring investigated that may someday be
employed clinically to improve flap physiology and flap
viability, allowing expanded flap applications
• Nevertheless, there is no substitute for proper flap
selection and design, and technical execution

88. No factors mentioned above should substitute:
• Proper flap selection and design
• Meticulous debridement & preparation of bed
• Careful flap elevation & inset
• Appropriate dressing application
• Post operative positioning
• Close post-operative clinical monitoring
– Hematoma
– Compression
– Kinking
– Anostomotic thrombosis
– Bleeding

89. Flap selection pre-op
• Surgical reconstruction goal
– Preservation & restoration of form & function while
minimizing morbidity
• In simple terms, “what is available, weighed against
what can be spared”

90. Flap selection pre-op
• Optimal reconstructive plan follows careful analysis of
flap selection based on:
a) Defect analysis (recipient site)
b) Patient factors (medical and functional status)
c) Reconstructive options
d) Cost of care
e) The surgeon & his institution

91. A) Defect analysis
• Location
• Size & surface area (after adequate debridement)
• Quality of the surrounding tissue
• Tissue missing or expose (eg hair, skin,mucosa,
subcutaneous tissue, muscle, vessels, nerves,
cartilage, bone)
– Which component need to be repaired?
– Which component can feasibly be replaced?

92. • Vascular status of wound or surrounding tissue
– Presence of vascular disease
– Evaluation of zone of injury (trauma)
– Adequate microcirculation to support grafts or local flaps
– Suitable recipient vessels available for free tissue transfer
– Previous radiation
– Previous surgery or trauma
• Infection & bacteriology of wound
• Future management concerns (eg need for post op
radiation, future surgical needs)
A) Defect analysis

93. B) Patient factors
• History & causes of current defect
o The need to treat the underlying cause
• Patient co-morbidities (influence the safety and success of
reconstructive options)
– Diabetes
– Tobacco use
– Obesity
– Advanced age
– Hypertension & IHD
– Pulmonary dysfunction
– Peripheral vascular disease
– Hematologic disorders
– Immunosuppresion

94. • Compliance
– Functional status, lifestyle & rehabilitative capacity of the patient
(eg neurological disorder)
• Patient’s expectation
– Meeting your own potential expectation?
• Life expectancy
– Complex reconstruction may be questionable
• Remember that the sacrifice of specific muscles for flap coverage
impacts individuals differently depending on other disabilities
present (eg paraplegia) or their occupation & lifestyle (eg
professional athlete vs accountant)
B) Patient factors

95. C) Reconstructive options
• Helps to organize
reconstructive
solutions in order
of complexity
• From most simple
solution to most
complex

96. • Factors related to the donor site selection include:
– Appropriate tissue match
o “Replace like with like”
– Length of the vascular pedicle
– Caliber of recipient vessels
– Surface area
– Volume
– Thickness of the flap
– Donor site morbidities
o Functional & aesthetic implications
C) Reconstructive options

97. D) Cost of care
• Both financial & psychological aspect
• Cost of life?
• Impact on quality of life

98. E) The surgeon & his institution
• Skill set
• Network of support (eg Facilities, staff, etc)

99. Flap monitoring
• Early detection of compromised flap
– Critical for early intervention, correction and salvage of flap
• The ideal flap monitoring system should be
o Simple
o Reliable
o Reproducible
o Sensitive
o Continuous
o Representative of the entire flap
o User friendly
o Easily interpreted
o Affordable
o Relatively unaffected by external environment

100. • Note that in certain situations,
such as buried flaps or free
flaps, the monitoring system
itself may need to be buried, or
the monitored area of the flap
may need to be used as a small
window to the overall flap status
• Limited access to the flap may
lead to faulty assessment

101. Flap monitoring modality
1. Physical methods
• Clinical monitoring
• Doppler probe
o Ultrasound Doppler probe
o Laser Doppler probe
• Temperature monitoring
• Fluorescein
2. Metabolism monitoring methods
• Transcutaneous oxygen tension
• Skin punctures and blood glucose measurements
• Continuous pH monitoring
• Photoplethysmography
• Microdialysis

102. Physical method
Clinical monitoring
Direct observation
o “Gold standard” of all monitoring systems
– Skin colour (compared with the adjacent normal skin colour)
– Warmth
– Capillary refill
 Healthy flap
– pink color within 1-2 seconds capillary refill
 Arterial insufficiency
– pale colour without capillary refill
 Venous congestion
– dusky color with exceptionally brisk refill
– Pin-prick bleed
 Bright pink oozing reflects a healthy flap
 Dark purplish oozing reflects compromised perfusion or venous
insufficiency

104. Physical method
Doppler probe
• The most widely accepted adjunct to clinical assessment
• Uses Doppler effect
o Measure the velocity of blood flow, as first described by Strandness
• Two main types of Doppler instruments
1. Ultrasound Doppler probe
– Uses reflected sound waves to measure the flow of blood cells within the larger
arteries and veins of tissues
2. Laser Doppler probe
– Measures the frequency shift of light rather than sound, and as such, has a limited
penetration of only 1-2 mm
• Advantages: Near 100% reliability, continuous & non invasive monitoring
• Disadvantages: non quantitative, single site information, and sensitive to
movement

105. 1. Conventional Doppler ultrasonography
• More than 40 years
• One of the simplest, most direct,
and most reproducible methods
• Vessels several centimeters deep
can easily be evaluated
• Arterial signal
– classic triphasic patterns
– Compromised arterial inflow
will lose its triphasic signal
pattern and become more
“watter-hammer” in nature or
disappear

106. • Venous signal
– Lower pitched & continuous
– Varying with respiratory cycle
– Easily augmented with gentle pressure of the flap
– Compromised venous outflow
 Venous signal absent or muted
 Lost of ability to augment venous flow by gentle compression
of the flap
• Limitation:
o Difficult in separating the flap signal from signals coming
from adjacent normal vessels deep to the flap
1. Conventional Doppler ultrasonography

107. • Miniature implantable Doppler probes,
surgically placed on the effluent vein
of a free flap
o Continously monitor venous
outflow
o No interference from adjacent
vessels
o Provide instant notification of
either arterial or venous occlusion
• Sensitivity 100%, false-negative rate
3%
• Allowed early re-exploration & 100%
flap salvage
• Becoming the standard of monitoring
of free flaps

108. 2. Laser Doppler study
• Measurement of skin blood
flow
• Provides continuous non
invasive monitoring of flaps
• A laser light prove is affixed
to a specific area of the
skin, and produces a
voltage output proportional
to the total flux of red blood
cells in the small volume of
tissue sampled

109. • Flowmeter value 30% of baseline
o Predicts flap survival
• Sensitivity 93%, specificity 94%
• Guidelines to improve accuracy:
o A fixed probe
o Continuous recordings
o Attention to physiologic fluctuations and trends
• Limitations:
– Sensitivity to minor changes in the probe position & angle on the
tissue surface with the patient’s movement
– Sensitivity to temperature changes
– Only a small amount of tissue is sampled at any one time
2. Laser Doppler study

110. Temperature monitoring
Physical method
One of the oldest & simplest indirect methods
A. Surface temperature
 Affected by local external environment
 Responds slowly to vascular compromise
 Sensitivity > 90%
B. Diferential thermometry
 More reliable
 Thermocouple probes are placed proximal and distal to a microvascular
anastomosis, and the temperature differential is recorded
o Temperature gradient exceeding 3˚C is significant
 This is particularly applicable for muscle flaps or buried flaps
 However, it is still affected by local environment variables

112. Physical monitoring
Fluorescein
• Provide direct assessment of skin perfusion
• Usually administered as an intravenous bolus (15mls/kg); then after 20
minutes, the tissue is examined with an ultraviolet lamp (wood’s lamp)
– Adequately perfused tissue fluoresces
– Inadequately perfused tissue, no fluorescence seen
• Only useful 18H post operatively

113. Perfusion fluorometry (dermofluorometry) with
dermofluorometer
• Provide quantitative measurement whereby a fibreoptic light is
used to measure and quantify the dermal fluorescence
• Continuous flap monitoring by serial fluorescein injections
(0.15mg/kg dose)
• Optimum dye fluorescence index (DFI) thresholds after flap
elevation (generally 30% and above is acceptable)
– 7% at 2 hours
– 27% at 5 hours
• Consistent, highly accurate and reproducible
Fluorescein

114. Metabolism monitoring methods
1. Transcutaneous oxygen tension
2. Skin puncture and blood glucose measurements
3. Photoplethysmography
4. Continuous pH monitoring
5. Microdialysis

115. 1. Transcutaneous oxygen (PO2) tension
• One of the oldest methods
• Uses a heated oxygen electrode
placed on the skin surface
• Measures trends over time
• Provides safe, reliable monitoring
of peripheral oxygenation in the
microcirculation that is rapid,
continuous and non invansive

116. • Limitation
– Subject to many other systemic factors affecting
oxygen transport and tissue oxygenation
• A more refined method uses an implantable
optochemical oxygen-sensing electrode (oxygen
optode), inserted in the subcutaneous tissue of the
flap
1. Transcutaneous oxygen (PO2) tension

117. 2. Skin punctures and blood glucose measurements
• Easy-to-use and efficient adjunct for
monitoring postoperative blood flow in
flaps
• Blood glucose level reduced in
congested flaps
• A cutoff value for the blood glucose is
62mg/dL
• Sensitivity 88% & specificity 82%
• Limitations:
– Not for ischaemic flaps because
sufficient blood cannot be obtained
to measure the glucose level in a
pinprick test
– Unreliable in diabetic patients

118. 3. Photoplethysmography
• Measures fluid volume by detecting variations in light
absorption by the skin
• Uses a light-emitting diode to transmit light into a tissue
• Reflected light from haemoglobin in the dermal capillary red
blood cells is received by a photo detector and is analysed
as light intensity along a frequency spectrum, removing
noise and allowing a means to distinguish between perfused
and non perfused tissues.

119. • Limitation:
– Measures flow in tissues only to a depth of 1 to 2 mm
• Provide a rapid, precise method to determine flap ischaemia
• Differentiate venous compromise versus arterial compromise
almost immediately after the onset of an ischaemic insult
• However, its use has never achieved widespread
acceptance
3. Photoplethysmography

120. 4. Continuous pH monitoring
• Uses a miniaturized glass pH probe that allows the
continuous measurement of subcutaneous tissue pH
– A rapid fall in tissue pH is seen in response to either arterial or
venous occlusion
• Reliable experimental tool but never reached widespread
clinical application

121. 5. Microdialysis
• An invasive, intermittent, indirect
monitoring technique
• A sampling technique that studies
the biochemistry of organs or
tissues
• A double-lumen microdialysis
catheter or probe similar in size to
an 18-gauge venous cannula is
placed (using an open needle)
under direct vision into the tissue
• Connected to a small pump,
which infuses physiologic fluid
through the catheter

122. • Across a dialysis membrane, this fluid equilibriates with
the interstitial fluid surrounding the catheter, and therefore
aliquots of the perfusate can be analysed on the tissue
content of glucose, lactate, pyruvate, and glycerol
metabolite concentrations.
– A falling glucose and rising lactate-to-pyruvate ratio indicates
indicates anaerobic metabolism (arterial compromise)
– A rising glycerol level reflects cell membrane damage
(venous congestion & arterial compromise)
5. Microdialysis

124. Salvage procedure for the failing
flap
• When recognized early and managed promptly (<6h),
compromised flaps have a 75% salvage rate when taken
back to the operating room
• If circulation cannot be re-established within 8 to 12 hours,
salvage of a free-tissue transfer may become impossible
because of the development of the no-reflow phenomenon
• Studies have demonstrated that venous thrombosis alone
is more common than either arterial or combined arterial
and venous thrombosis

125. Flap monitoring regime
• Majority (>80%) of thrombi occurred within the first 2 post
operative days
• 95% circulatory compromise occurs within 72 hours after
surgery
• This decreases to 10% after postoperative day 3
• Most centres recommend a minimum of hourly monitoring for
the first 24-48 hours

126. Thank you