Skin flap physiology
Skin flap physiology
• Ensuring vascular supply
• Goal : maintenance adequate perfusion to meet metabolic demands
Physic of flow
• hagen poiseuille equation
Critical closing pressure
-when tissue pressure exceeds intracapillart pressure : capillary blood vessel collapse
-LaPlace’ law : surface tension on vessel increase with vessel radius , exponential rise in flow
Anatomy and physiology of skin
• Skin : sensory organ , protective organ
• Epidermis , dermis ,subcutaneous tissue
• Epidermis : stratified squamous epithelium , metabolically active but avascular
• Sensory nerve : dermatome
Zone I : Macrocirculatory system
• Cardiopulmonary system , conduit for blood flow (artery&vein)
,Musculocutaneous artery , Septocutaneous artery
• Vascular tone : anatomic neural system
• Essential for flap survival
• Free microvascular tissue transfer : zone I manipulation
Zone II : Capillary system (microcirculation)
• Microcirculation : arteriole , venule , capillaries , lymphatic buds
• Cutaneous capillary system and arteriovenous shunt : nutritional support and thermoregulation
• Adequate systemic vascular pressure , preshunt and precapillary sphincter regulate distribution
cutaneous blood flow
• Postganglionic terminal of cutaneous symphathetic nerves
• Norepinephrine found in area of cutaneous arterioles
Zone II : Capillary symtem (microcirculation)
• Preshunt sphincter
• Thermoregulation
• Systemic blood pressure by vasoactive substance (Norepinephrine)
• Effect of blood flow
• Blood viscosity : Hct , Serum protein
• Erythrocyte deformability , aggregation
• Temperature
Zone III : interstitial system
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Interstitial space : nutrient delivery by diffusion and convection
lymphatic system : remove excessive fluid , remove intersitial protein
interstitial fluid is determined by capillary permeability
If edema : diffusion distances increase and increase tissue pressure
Zone III : interstitial system
Starling-Landis equation
-Increase venous pressure limits interstitial resorption and
formation transudate
-Capillary hyperpermeability has been found throughout
ischemic flap
Zone IV : Cellular system
• Intracellular space : endpoint for nutrient transport and origin of metabolic waste
• Specific membrance proteins maintain cell homeostasis (Na-K pump)
• Loss of oxygen or ATP : increase intracellular osmotic pressure (loss of
permeability)
• Arterial occlusion within 10 mins : cell begin swelling ->prolong : cell lysis and flap
necrosis
Survival of flap = survival of cell
Recovery from flap elevation
• Neovascularization begins 3-4 days after flap transposition
• Free flap pedicle is no longer monitored after 1 week
• Angiogenic growth factor can stimulate capillary growth over distance
of 2-5 mm
Introduction
• Flap failure – ischemic necrosis
• Free flap – 5-10 %
• Partial VS Total
• Additional operation – cost $40000 – $68000
• Additional surgeon reimbursement – cost $5000 - $35000
Scope
• Pathophysiology of flap failure
• Surgical manipulation for augmentation of pedicle flap viability
• Pharmacological therapy for augmentation of pedicle and free flap
viability
Scope
• Pathophysiology of flap failure
• Vasospasm and thrombosis in the pathogenesis of pedicle and
free flap failure
• Ischemia reperfusion injury in free flap surgery
• Xanthine dehydrogenase/xanthine oxidase enzyme system
• Neutrophilic nicotinamide adenine diphosphate (NADPH) and
myeloperoxidase (MPO) enzyme system
• Intracellular Ca 2+ overload
• Surgical manipulation for augmentation of pedicle flap viability
• Pharmacological therapy for augmentation of pedicle and free flap
viability
Scope
• Pathophysiology of flap failure
• Vasospasm and thrombosis in the pathogenesis of pedicle and
free flap failure
• Ischemia reperfusion injury in free flap surgery
• Xanthine dehydrogenase/xanthine oxidase enzyme system
• Neutrophilic nicotinamide adenine diphosphate (NADPH) and
myeloperoxidase (MPO) enzyme system
• Intracellular Ca 2+ overload
• Surgical manipulation for augmentation of pedicle flap viability
• Pharmacological therapy for augmentation of pedicle and free flap
viability
Pathophysiology of flap failure
• Vasospasm and thrombosis in pathogenesis of pedicle and free flap failure
• Ischemic necrosis occurs in distal portion of both pedicle and free flap
• Vasospasm and thrombosis due to surgical trauma and insufficient distal vascularity
• Unclear pathogenic mechanism.
• role of vasoactive neurohumoral substances in the local regulation of peripheral
vascular tone
Pathophysiology of flap failure
Endothelium-derived relaxing factors
(EDRFs)
Endothelium-derived contracting
factors (EDCFs)
• Prostacyclin (PGI2)
• Nitric oxide (NO)
• Thromboxane A2 (TXA2)
• Endothelin-1 (ET-1)
-Relaxation of vascular smooth muscle
-Inhibit platelet aggregation
Increase vascular tone
Balance effect between EDRFs & EDCFs
Surgical trauma ->imbalance ->Vasospasm&thrombosis
• Traumatized sympathetic nerve endings and vascular
endothelium
• ↑ Vasoconstriction + intravas.Plt. aggregation
• Sympathetic nerve endings – NE (vasoconstriction+platelet
aggregation)
• Platelets – leukotrienes, serotonin (5HT 2 ), TXA2
• Endothelial cells – ET-1
• Hemolyzed RBCs - Hb(vasoconstriction)
• Mast cells – histamine (tissue edema)
• ↓ Vasodilatation
• Endothelial cells (traumatized)
• ↓ EDRFs – PGI2, NO
• ↓ COMT + MAO (degradation enzyme of NE, 5HT2)
In reperfusion of ischemic blood vessels
• Superoxide radicals (Ö2)
• Produced by platelets, neutrophils, endothelial cells
• Endothelial cells (traumatized)
• Decreased production of NO (Ö2 scavenger)
Free radicals can damage vascular walls during reperfusion
Scope
• Pathophysiology of flap failure
• Vasospasm and thrombosis in the pathogenesis of pedicle and
free flap failure
• Ischemia reperfusion injury in free flap surgery
• Xanthine dehydrogenase/xanthine oxidase enzyme system
• Neutrophilic nicotinamide adenine diphosphate (NADPH) and
myeloperoxidase (MPO) enzyme system
• Intracellular Ca 2+ overload
• Surgical manipulation for augmentation of pedicle flap viability
• Pharmacological therapy for augmentation of pedicle and free flap
viability
Pathophysiology of flap failure
• Xanthine dehydrogenase/xanthine oxidase enzyme system in
pathogenesis of ischemia-reperfusion injury in free flap surgery
• Warm global ischemia
• Human muscle – 2-2.5 hours
• Human skin – 6-8 hours
• Excessive ischemia >> energy depletion + formation of Ö2 >> Ischemia-reperfusion
injury
• Hypoxanthine/xanthine oxidase system
• A main source of oxyradicals in ischemic rat skin and muscle
• Allopurinol, tungsten diet : xanthine oxidase inhibitor treatment
• Pig and human skin contain minimal xanthine oxidase activity (<
40 times)
most potent cytotoxic hydroxyl radical
Scope
• Pathophysiology of flap failure
• Vasospasm and thrombosis in the pathogenesis of pedicle and
free flap failure
• Ischemia reperfusion injury in free flap surgery
• Xanthine dehydrogenase/xanthine oxidase enzyme system
• Neutrophilic nicotinamide adenine diphosphate (NADPH) and
myeloperoxidase (MPO) enzyme system
• Intracellular Ca 2+ overload
• Surgical manipulation for augmentation of pedicle flap viability
• Pharmacological therapy for augmentation of pedicle and free flap
viability
Pathophysiology of flap failure
• Neutrophilic nicotinamide adenine diphosphate (NADPH) and
myeloperoxidase (MPO) enzyme system in pathogenesis of
ischemia/reperfusion injury in free flap surgery
• Neutrophils produce Ö2 via NADPH oxidase, MPO
• Treatment with
• Monoclonal Ab against neutrophil-endothelium adhesion molecules
• Attenuated ischemia-reperfusion-induced skin necrosis in rabbit, rat, pig
• Mechlorethamine(Neutrophil depletion)
• Reduced necrosis in pig, dog
• Species difference
• Not the same outcome in human
Scope
• Pathophysiology of flap failure
• Vasospasm and thrombosis in the pathogenesis of pedicle and
free flap failure
• Ischemia reperfusion injury in free flap surgery
• Xanthine dehydrogenase/xanthine oxidase enzyme system
• Neutrophilic nicotinamide adenine diphosphate (NADPH) and
myeloperoxidase (MPO) enzyme system
• Intracellular Ca 2+ overload
• Surgical manipulation for augmentation of pedicle flap viability
• Pharmacological therapy for augmentation of pedicle and free flap
viability
Pathophysiology of flap failure
• Intracellular Ca2+ overload in pathogenesis of ischemia-reperfusion
injury in free flap failure
• Experimental evidence – intracellular Ca2+ overload >> causing cell death
Inactivation of energy-dependent Na+-K+ATPase pump
MPTP
At reperfusion, rapid washout of extracellular H+
↑ Extrusion of intracellular H+
↑ Accumulation of intracellular Na+
↑ Cytosolic Ca2+ overload
No-reflow phenomenon
Pathogenesis of no-reflow phenomenon in free flap surgery
• May et al.: Rabbit island epigastric skin free flap model >> ischemia induce:
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Swelling of endothelial and parenchymal cell
Narrowing of capillary lumen
Intravascular aggregation of blood cells
Leakage of intravascular fluid into interstitium(form edema)
• Length of ischemic time 1 >> 8 hours
• A point of irreversible obstruction after 12 hours >> no reflow and death of
flap
Pathophysiology of flap failure
• Pathogenesis of no-reflow phenomenon the skeletal muscle of
laboratory animals
• 3 pathogenic mechanisms
• (1) oxygen-derived free radicals causing damage in the endothelial and parenchymal cells
• (2) cell membrane damage allowing Ca2+ influx, resulting in intracellular overload
• (3) change in arachidonic acid metabolism resulting in synthesis of less vasodilating and
antithrombotic PGI2 and increased synthesis of vasoconstricting and thrombotic TXA2
Scope
• Pathophysiology of flap failure
• Vasospasm and thrombosis in the pathogenesis of pedicle and free flap
failure
• Xanthine dehydrogenase/xanthine oxidase enzyme system in
pathogenesis of ischemiareperfusion injury in free flap surgery
• Neutrophilic nicotinamide adenine diphosphate (NADPH) and
myeloperoxidase (MPO) enzyme system in pathogenesis of
ischemia/reperfusion injury in free flap surgery
• Intracellular Ca 2+ overload in pathogenesis of ischemia–reperfusion
injury in free flap failure
• Surgical manipulation for augmentation of pedicle flap viability
• Pharmacological therapy for augmentation of pedicle and free flap viability
Surgical manipulation for augmentation of
pedicle flap viability
• Flap design in augmentation of pedicle flap viability
• Surgical delay in augmentation of pedicle flap viability
• Vascular delay in augmentation of pedicle flap viability
• Mechanism of surgical delay
Surgical manipulation for augmentation of
pedicle flap viability
• Flap design in augmentation of pedicle
flap viability
• The viable length of a skin flap depends on
the width of the pedicle – WRONG!!!
• The balance between perfusion pressure
and vascular resistance
• Increasing the width of pedicle adds
additional vessels of the same type and
perfusion pressure
one of the surgical manipulations to augment flap viability >> conversion of a random-pattern skin
flap to axial skin flap by incorporating a direct artery or a larger perforator.
Surgical manipulation for augmentation of
pedicle flap viability
• Surgical delay in augmentation of pedicle flap
viability
• Proven techniques for augmenting flap viability
• 2-3 stages
• Undermining to form a bipedicle flap
• The third side (distal end) is cut
• Surgical delay increases skin flap capillary blood
flow between 2-7 days
• Mainly in distal random portion
• Studies in pig random pattern skin flaps
Surgical manipulation for augmentation of
pedicle flap viability
• Vascular delay in augmentation of pedicle flap viability
• dividing distal perforating arteries at 1–2 weeks prior to raising the muscle
flaps
• Ligation of DIEA 2-4 weeks before flap surgery augmented skin blood supply
and viability in TRAM flap
• Vascular delay by embolization
Surgical + vascular delay
• Proven clinically effective >> cost and time consuming
• “Recharging” of pedicle TRAM
• Free flap >> improve blood flow and viability
• Not always available and expensive
Mechanism of surgical delay in augmentation of
pedicle flap viability
1. Reduce arteriovenous (AV) shunt flow
2. Deplete vasoconstriction and prothrombotic substances in the skin flap
3. Induce vascular territory expansion by opening existing choke arteries
4. Induce angiogenesis
Mechanism of surgical delay in augmentation of
pedicle flap viability
1. Surgical delay procedure reduces arteriovenous (AV) shunt flow
• Distal ischemic necrosis was caused by opening of AV shunt flow as a result of sympathetic
denervation
• Shunt flow occurs throughout the flap
• Proximal flow is sufficient to supply both AV and capillary blood flow
• Shunting became lethal in distal areas
• In surgical delay, the bipedicle skin flap provided sufficient blood supply during the early
period of sympathetic denervation and opening of AV shunts.
• Surgical delay allows skin flap to recover from its hyperadrenergic state
• Species differences – again!!
• AV shunt flow in:
• Pig skin – 60% of total blood flow
• Rat skin – 10% of total blood flow
• Human skin – 1% of total blood flow
Mechanism of surgical delay in augmentation of
pedicle flap viability
2. Surgical delay procedure depletes
vasoconstriction and prothrombotic
substances in the skin flap
• Surgical delay reduces local production and
allow time to deplete vasoconstricting and
prothrombotic substances
• However, the outcomes of vasodilating and
antithrombotic drugs are disappointing
Mechanism of surgical delay in augmentation of
pedicle flap viability
3.Surgical delay procedure induces vascular
territory expansion by opening existing choke
arteries
• In delayed random-pattern pig skin flaps
• Capillary blood flow increased within 2 days of delay
(maximum between 2-3 days), and remained unchanged
between 4-14 days of delay without an increase in density
of arteries
• Increase in capillary blood flow occurred mainly in distal
portion
• Angiosome territory expansion by opening of
existing choke blood vessels
Mechanism of surgical delay in augmentation of
pedicle flap viability
4. Surgical delay procedure induces angiogenesis
• A significant increase in gene expression of VEGF, FGF in skin paddle of rat
TRAM flaps within 12 hours of vascular delay
• Induce vasodilation and angiogenesis?? Need further study
Scope
• Pathophysiology of flap failure
• Vasospasm and thrombosis in the pathogenesis of pedicle and free flap
failure
• Xanthine dehydrogenase/xanthine oxidase enzyme system in
pathogenesis of ischemiareperfusion injury in free flap surgery
• Neutrophilic nicotinamide adenine diphosphate (NADPH) and
myeloperoxidase (MPO) enzyme system in pathogenesis of
ischemia/reperfusion injury in free flap surgery
• Intracellular Ca 2+ overload in pathogenesis of ischemia–reperfusion
injury in free flap failure
• Surgical manipulation for augmentation of pedicle flap viability
• Pharmacological therapy for augmentation of pedicle and free flap viability
Pharmacological therapy for augmentation of
pedicle flap viability
• Drug therapy against vasoconstriction and thrombosis in pedicle and
free flap surgery
• Recent research in drug therapy focused on vasodilation, antithrombosis,
inhibition of neutrophil from adherence and accumulation
• Controversial, inconclusive result comparing with surgical delay
• Studies performed in loose-skin animals (rats, rabbits)
• there is no effective drug therapy which can mimic surgical or vascular delay in
augmenting skin flap viability.
Pharmacological therapy for augmentation of
pedicle flap viability
• Angiogenic cytokine protein or gene therapy for augmentation of
pedicle flap viability
• VEGF, FGF, PDGF induce angiogenesis
• Subdermal injection >> increased viability of flaps in loose-skin animals
• VEGF165
• Early stage (within 6 hours) – vasodilator effect >> inducing synthesis/release of NO
• Late stage – angiogenic effect(i.e., increase in capillary density)
• Biological half-life 30-45 min (normoxic), 6-8 hours (hypoxic)
• Protein therapy >> Gene therapy(น่าจะดีกว่า)
• VEGF165 >> cDNA of VEGF165 (Ad.VEGF165)>> increased VEGF expression
Pharmacological therapy for augmentation of
pedicle flap viability
• Ad.VEGF165
• cDNA of VEGF165
• adenoviral vectors encoding the cDNA of VEGF 165
• Intradermal/subcutaneous injection sing liposomal/adenoviral vectors
• Increased number of capillaries and arterioles in the skin of rat TRAM flaps
• Efficacy ระหว่าง VEGF 165 protein and gene therapyไม่ตา่ ง
• Flap viability 15-20% lower than surgical delay
Pharmacological therapy for augmentation of
free flap viability
• Vasospasm, thrombosis, and ischemia–reperfusion injury are the main causes
of free flap failure.
1. Drug therapy for prevention of vasospasm and thrombosis in free flap surgery
• Anticoagulant agents
• Thrombolytic agents
• Antispasmodic agents
2. Preischemic and postischemic conditioning against ischemia-reperfusion
injury in free flap surgery
• Local preischemic conditioning
• Remote preischemic conditioning
• Postischemic conditioning
Pharmacological therapy for augmentation of
free flap viability
• Vasospasm, thrombosis, and ischemia–reperfusion injury are the main causes
of free flap failure.
1. Drug therapy for prevention of vasospasm and thrombosis in free flap surgery
• Anticoagulant agents
• Thrombolytic agents
• Antispasmodic agents
2. Preischemic and postischemic conditioning against ischemia-reperfusion
injury in free flap surgery
• Local preischemic conditioning
• Remote preischemic conditioning
• Postischemic conditioning
Pharmacological therapy for augmentation of
free flap viability
1. Drug therapy for prevention of vasospasm and thrombosis in free flap surgery
• Anticoagulant agents ; unclear efficacy
• Heparin
• Reduce platelet aggregation , activates antithrombin III
• Effective in rabbit but in human>>no sig. effect
• Antithrombosis VS Bleeding tendency; low dose(3000-5000iu IV) ไม่เพิม
่ hematoma แต่ก็ไม่ชว่ ยลดthrombosis >> need
more study for effective dose
• 100-150 u/kg IV before cross-cramping
• 50 u/kg IV every 45-50 min until complete anastomosis
• Aspirin
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Inhibit plt cyclooxygenation production of TXA2 ,endothelium production of PGI2(minimal)
Low-dose aspirin 40-325 mg (do not cause post-op hematoma in free flaps)
Require > 24 hours for maximal effect
Preventing coronary graft occlusion when given preoperatively or within 24 hours
• Dextran (vol. expansion + antithrombogenic effect)
• Dextran 40 หวังผล decreases platelet aggregation and improves blood flow in free flap surgery
• Side-effects – anaphylaxis, pulmonary/cerebral edema, renal failure
• there is clinical evidence indicate low-molecular-weight dextran treatment may not be effective in augmenting free
flap viability.
Pharmacological therapy for augmentation of
free flap viability
• Thrombolytic agents(small study orcase report)
• Failing free flaps unresponsive to standard interventions
• Streptokinase, rt-PA(dose controversy)
• Antispasmodic agents
• Papaverine(local injection)
• An opiate alkaloid
• Inhibits phosphodiesterase >> ↑ cAMP >> vasodilatation
• Nifedipine(oral)
• A calcium channel blocker
• Inhibition of calcium influx into the arterial smooth-muscle cells>> smooth muscle cell relaxation
• Lidocaine(local injection)
• Vasodilatation
• Effect on Na+/Ca2+ ion exchanger pump >> reduces intacellular Ca2+
Pharmacological therapy for augmentation of
free flap viability
• Vasospasm, thrombosis, and ischemia–reperfusion injury are the main causes
of free flap failure.
1. Drug therapy for prevention of vasospasm and thrombosis in free flap surgery
• Anticoagulant agents
• Thrombolytic agents
• Antispasmodic agents
2. Preischemic and postischemic conditioning against ischemia-reperfusion
injury in free flap surgery
• Local preischemic conditioning
• Remote preischemic conditioning
• Postischemic conditioning
Preischemic and postischemic conditioning against
ischemia-reperfusion injury in free flap surgery
• Local preischemic conditioning against ischemia-reperfusion injury in skeletal
muscle
• Mounsey et al. – study in pig muscle flaps
• Instigation of 3 cycles of 10 min occlusion/reperfusion in pig LD muscle flaps with a vascular
clamp
• Reduced muscle infarction by 40-50% when subjected to 4 hours of warm ischemia + 48 hours
of reperfusion
• Vascular clamping >> risk of damaging the blood vessels
• identification of pharmacological treatment to mimic local preischemic conditioning.
• Adenosine A1 receptor-protein kinase C-mitochondrial KATP channel-linked
events
• Efficacy of preischemic conditioning in ex vivo human rectus abdominis muscle
strips?
Preischemic and postischemic conditioning against
ischemia-reperfusion injury in free flap surgery
• Remote preischemic conditioning against ischemiareperfusion injury in skeletal muscle
• Addison et al.
• Instigation of 3 cycles of 10-min of occlusion/reperfusion
in a hind limb of the pig by tourniquet application under
GA
• Protected multiple skeletal muscles from infarction
when subjected to 4 hours of ischemia + 48 hours of
reperfusion
• Sarcolemmal and mitochondrial KATP channels play
central role!!
Preischemic and postischemic conditioning against
ischemia-reperfusion injury in free flap surgery
• Remote preischemic conditioning against ischemia-reperfusion injury in skeletal
muscle
• Future approach
• Identify a non-hypotensive prophylactic drug to be taken PO 24 hours before surgery
• Achieving 48 hours of perioperative protection of skeletal muscle from ischemia-reperfusion
injury
• Recently, we observed in pigs that the clinical drug nicorandil induced 48h uninterrupted
muscle infarct protection.
Preischemic and postischemic conditioning against
ischemia-reperfusion injury in free flap surgery
• Postischemic conditioning for augmentation of free flap viability
• Role in prolong ischemic time >> salvage from ischemic reperfusion injury
• Khiabani and Kerrigan
• local intra-arterial infusion of the NO donor SIN-1 to pig muscle flaps and cutaneous flaps after 6 hours of
ischemia
• effective in salvaging flap from reperfusion injury
• McAllister et al.
• Instigation of 4 cycles of 30-second reperfusion/reocclusion at onset of reperfusion after 4 hours of ischemia
• Reduced pig LD muscle flap infarction by 50% (assessing at 48 hours)
• Lowering of mitochondrial free Ca2+ content >> closing of mitochondrial permeability transitional pores (mPTP) >>
increase in muscle ATP content
• Cyclosporine A (mPTP opening inhibitor)
• IV injection 10 mg/kg at 5 min before reperfusion in pig muscle flaps
• Mimicking the protective effect of postischemic conditioning
• Effective oral dose?
• Undergoing study in ex vivo human muscle
• Cariporide (Na+/H+ exchanger inhibitor)
• Preischemic/postischemic treatment, IV 3mg/kg
• Decrease in mitochondrial free Ca2+ content and infarct size in pig LD muscle flaps when subjected to 4 hours of
ischemia + 48 hours of reperfusion
Conclusion and future directions
• Surgical and vascular delay
• The only proven technique in augmenting flap viability
• Preischemic/postischemic conditioning
• Effective protection for ischemia-reperfusion injury
• Reticent to conduct due to invasiveness/time-consuming
• VEGF165 gene/protein therapy
• 15-20% efficacy < surgical delay
• Angiopoietin-2 (induce arteriogenesis)
• Efficacy??
• Angiopoietin-2 + VEGF165 = ??
• Understanding the mechanism of preischemic/postischemic conditioning
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Inflammation
Na+/H+ exchanger
Mitochondrial free Ca2+ content
Opening of the mPTP
Introduction
Microsurgery
• surgery requiring the operating microscope
• microvascular surgery (surgery on blood vessels around 1
mm), microneural surgery, micro- lymphatic surgery, and
microtubular surgery
• Supramicrosurgery: extreme microsurgery, anastomoses of
vessels around 0.5 mm in diameter (0.3–0.8 mm), invaluable
in lymphatic reconstruction and perforator-to-perforator
anastomosis
• some of these procedures are performed under loupe
magnification (×2.5–8), including vessel coaptation,
especially when the diameter is not too small (around 3 mm)
• high price, demanding experience and resources
Tools
Surgical Microscope
• The modern operating microscope, with its refined optics up to
40x magnification
• Low magnification (6x–12x): vessel preparation and suture tying
• Middle magnification (15x–19x): suture placement
• High magnification: very small vessel anastomosis and
inspection of the anastomosis
Tools
Loupes
• provide magnifications of 2.5x–8x
• Microscopes required: anastomoses in children, vessels 1.5 mm or less in diameter
Tools
Loupes: 2 types
• Compound (galilean)
• 2 magnifying lenses separated by air -> higher magnification, greater depth of
field, and better working distance
• image quality distorted at magnifications above 2.5×
• create a “halo” effect at the periphery of the visual field which may disturb the
surgeon
• Prismatic loupe
• higher optical quality because of a Schmidt prism
• series of mirror reflections inside the loupe -> improved magnification, wider fields of
view, and longer depths of field or working distance
• 30–40% heavier, more expensive
Tools
Choosing Loupes
• 2.5x  for hand surgery and flap harvesting
• 3.5 – 4.5x  perforator dissection or anastomoses
• Higher than 4.5x tend to be cumbersome and too
heavy for daily use
• both field and depth of field decrease with
increasing magnification, while the weight of the
loupes increases
Microsurgical Instruments
Essential features
• fine tips to spread, hold, or cut delicate tissue and suture
• nonreflective surface and comfortable handles
• spring-loaded -> the right spring tension; too weak -> close all the way just by
holding instrument; too firm -> hand will fatigue
• Made of heat-hardened stain- less steel -> more resistant to wear and tear
• prone to magnetization -> stored on demagnetized/ nonmagnetic shelves.
• High chloride concentrations should be avoided as they lead to pitting and
corrosion
• Round or flat handle, 10–18 cm in length depending on surgeon preference and
depth of working field.
• shorter instruments: anastomosis is closer to the surface(hand surgery)
• instruments longer than 18 cm: free tissue transfer
Microsurgical Instruments
• Scissors
• Needle holder
• in inexperienced hands, the locking and unlocking maneuvers
easily damage the needle and significant trauma to the tissues
handled; unlocking needle holder is preferred.
• Forceps
• Vascular clamps
• Bipolar coagulator
• conducts current between the tips of the jeweler’s forceps ->
producing heat damage only within a very small area between
the instrument tips
• precise coagulation of small branches as close as 2 mm to the
main vessel
• Irrigation and suction
Microsurgical Instruments
Microsutures
• most widely used sutures
• 9-0 monofilament nylon on a 100-μm curved
needle
• 10-0 nylon on a 75-μm needle.
• based on the vessel wall thickness and diameter
• 9-0 sutures used for vessels of 2 mm or more in
diameter
• 10-0 for those between 1 and 2 mm in diameter.
Special considerations for supermicrosurgery
• Supermicrosurgery
• anastomosis of blood vessels smaller than 1 mm (0.3-0.8mm)
• Special instruments are crucial for success.
• surgical microscope with the highest currently available
magnifying power, 50× magnification
• thinnest titanium forceps
• smallest surgical needle (12-0 nylon).
• The microscope has high-power (50×) magnification and allows
a 20-cm working distance, which was impossible with
microscopes of 20× magnification
Anastomotic devices
Coupling devices
• Mostly for venous anastomosis
• Can also apply to arterial anastomosis
• vv range 0.8-4.5 mm (rings come in a variety of sizes:1 to
4 mm in diameter)
• maximal wall thickness of 0.5 mm
• suitable for both end-to-end and end-to-side anastomosis
• Types
• permanent rigid ring
• absorbable anastomotic coupler(70 d - 30 wk)
Anastomotic devices
Contraindication
• peripheral vascular disease
• areas with ongoing radiation therapy
• active infection
• concurrent diabetes
• corticosteroid therapy
• Contraindications of using this device on arterial anastomosis
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thick-walled vessels (do not adequately evert)
diameter discrepancies of more than 1.5 : 1 ratio
nonpliable vessels stiffened by prior radiotherapy or calcification
any artery less than 1.5 mm in diameter
Coupling device
Coupling device
Anastomotic devices
• All anastomotic devices are essentially for use on
healthy vessels only;
• the veins should be pliable
• the arteries soft to allow eversion
• the vessel ends minimally size-discrepant
Other nonsuture methods
• Adhesive glue :1.fibrin glue 2.Cyanoacrylate glue
• 1.Fibrin glues  Beware of luminal obstruction
• ต ้อง approximate vessel walls with conventional sutures ก่อน
(ชว่ ย reduce total number of suture required,faster union)
• prevent the glue entering the vessel lumen and potential for
allergic & anaphylaxis
• 2.Cyanoacrylate glues  histotoxicity
• Thermal or laser welding  the fear of possible weakening at the
site of the anastomosis with consequent pseudoaneurysm
formation
General principles of microvascular surgery
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Basic : calm, patience, good assistant, hand skill
Planning and position : surgeon comfortable
Securing the flap, flap inset
Selection and dissection of recipient vessels
• away from trauma / Radiation zone
• check quality recipient VV ( wall damage, thrombus, spurt test)
• Recipient vessels
• deep, greater length -> orientate in a more desirable
position
Preparation of vessel
Lumens: inspected for irregularities
• intimal tears or separation from the media
• Thrombi
• atherosclerotic plaques
• friable calcified walls
Preparation of vessel
• Debris: irrigated, atraumatically removed with microforceps.
• Failing remove -> vessel should be cut back, without
compromising pedicle length -> healthier segment (interpositional
vein graft)
• Inadequate debridement of vessels is often a major cause of flap
failure.
3 principal layers
• Tunica intima (the innermost) = single layer of endothelium
• Tunica media
• smooth-muscle cells = the thickest layer of the arterial wall.
• In veins: much thinner/ indistinguishable.
• Tunica adventitia (outermost)
• loose areolar connective tissue: contains the vasa vasorum,
which nourishes the vessel wall
• Veins consist of the same layers as arteries, but the layers are
less defined, particularly with regard to the tunica media which
in some lesser veins is almost indistinguishable
• Adventitia peeled off or sharply trimmed to a distance of
3–4 mm from anastomotic site.
• The main purpose: improve visualization of vessel ends,
prevent adventitia falling into lumen
• more radical trimming -> cutting tented adventitia parallel
to length of vessel
• Avoid overly aggressive adventitial stripping as this may
cause necrosis of the vessel wall -> false aneurysms
• Vessel lumens are gently
dilated
• prevent vasospasm
• intraluminal blood flushed
out with heparinized saline
• overcome minor degrees
of size discrepancy.
• Hemostat artery forceps is
used to bring the two clamps > vessel ends are just touching
or with minimal overlap
Anastomotic sequence
• no consensus
• Depend on: vessel position (deeper, difficult-to-reach being
repaired first)
• Arterial repair first may be a sensible choice
• shorten warm ischemia time.
• reveal more dominant venous to aid selection donor vein
• detect twist, kink, compression in pedicle
• Disadvantages
• flap start bleeding and affect anastomosis of vein.
• Subsequent venous congestion may increase bleeding
from flap edges and allow a buildup of free radicals.
• To avoid: second vein intermittently released to allow
drainage
Anastomotic sequence
• Alternatively, venous anastomosis could be performed first
• allows for better adjustment of the pedicle length
• Con: delay revascularization of the flap
• Experimental study: highest flap failure if arterial anastomosis
was performed first and immediately unclamped -> venous
congestion
• Our practice (more than 1000 free flaps/year)
• Repair artery first
• unclamped as vein repaired
Microvascular anastomosis techniques
Suturing techniques
• End-to-end anastomosis
• End-to-side anastomosis
End-to-end anastomosis
• using interrupted sutures ->
most common method
• simple and appropriate for
most arterial, venous
anastomoses
• avoiding luminal narrowing at
the anastomotic site
• opposing 2 intimal edges
closely
• 3 stay sutures were placed at
120° from each other.
Anastomosis between size-discrepant vessels
• Vessel mismatches of up to 4 : 1 can be safely anastomosed end-toend
• gently stretch smaller vessel mechanically
• placing a fish-mouth/ obliquely cutting
•
angles >30 degrees of oblique cut may cause kinking -> should be avoided
• anastomosis distal to side branch and opening up distal wall
Anastomosis between size-discrepant vessels
• When the discrepancy is greater than 3 : 1
• consider an end-to-side anastomosis, a vein graft to graduate the discrepancy, or
using a side branch of the larger vessel
• Remaining vessel can be directly sutured to itself taper the vessel and
minimize turbulence
ระวัง มุม>30 oblique cut อาจทาให ้ kink ได ้
Difficult anastomosis
• Vertically oriented anastomosis
ปรับเปน horizontal oriented จะง่ายกว่า หรือลดขนาด magnification
• Atherosclerosis and loose intima
ั เจน ให ้ trim จนได ้ good vv หรือเปลีย
้
- เห็น plaque ชด
่ นเสนใหม่
- loose intima ระวังเกิด intimal separation
- Vascular clamp ไม่แน่นไป
- Round needle
- Smallest suture
- Avoid vessel dilatation
- เย็บแน่นไปจะ erode plaque
- Prefer end to end fashion
Microvascular grafts
Vein grafts
• I/C : gap resulting from short pedicle, tension at anastomosis, size
mismatch, place anastomosis outside zone of injury.
• Workhorse: great/lesser saphenous (alternatives include the cephalic and
the comitant veins, volar forearm and dorsal foot
• need dilatation prior to anastomosis
Arterial graft
• advantages over vein grafts
• absence of valves, similar luminal and wall-thickness
• produce more prostacyclin -> greater antithrombogenic
• not been shown to have significant advantages in the context of
microvascular surgery
• Harvested: subscapular tree, ant/posterior interosseous arteries,
radial or ulnar, deep or superficial inferior epigastric, dorsalis pedis
Testing patency
1. Uplift test
2. Empty and refill test
• more traumatic -> performed
when needed
• preferably on veins (minimize
spasm or intima separation)
General aspects of free-flap surgery
• Advantages
• Freedom of choice of donor
• Can be tailored to meet specific
requirements
• Single-stage procedure
• better cutaneous blood flow
• Disadvantages
• Long operative time
• Lack of quality recipient vessels
• Need for highly skill
• Flap failure
Pre-op evaluation
• Patient factors
• Healthy  diabetic, hypertensive control,PAD
• Age  not a contraindication
• Smoking  not affect vessel patency, flap survival and
reoperation rates, but increased donor site complications
• stop smoking 4 wks before sx
• Obesity  increased risks (flap loss, hematoma seroma, donor
complications) with BMI >30
• Alcohol  increased flap failure, nonflap related
complications(post op ALC withdrawal)
Pre-op evaluation
• Evaluation of recipient and donor sites
• Irradiation  increased flap failure?
• Author : increased risk of reoperation and
complications
• meticulous tech, anastomosis site out of zone RT
• Delayed neovascularization
• Infection or traumatic wounds : Debridement ให ้ดีกอ
่ น
• Doppler device , CTA for perforator selection
• Routine preop angiography  unjustified
• แนะนาทาใน abnormal distal pulse
Pre-op evaluation
• Choice of flap
• Does this defect need a free flap?
• Size & tissue component
• Timing
• Acute reconstruction  immediate within 24 hr, urgent within 72 hr
• author : adequate debridement
• immediate cover must be considered if vital structures are exposed
Microvascular anesthesia
• Good pain, temperature, and sympathetic control to prevent vasospasm
and vasoconstriction
• Finetuning of blood pressure
• Adequate fluid management
• slight hemodilution to maintain high cardiac output and low systemic vascular
resistance
Choice of anesthetic
•
•
•
•
Several anesthetic agents : vasoactive
Isoflurane , sympatholytic vasodilator : better flap survival
Nitrous oxide : vasoconstriction
Verapamil , lidocaine : decrease skin flap necrosis (pedicle flap)
• Fluid overload : flap edema
Postoperative management,
complications, and outcomes
Post op care
• Key : ไม่กด pressure ลงบน flap & prevent vasospasm
• ห ้าม Circumferencial dressing
• Position prevent direct pressure on flap
• +/-External fixation for extremity : Slab ,K-wire , external fix
• ROOM warm
• Adequete urine output&SBP
• Hct 25-35%
• Pain control
• Avoid caffeine&nicotine
Monitoring
• There is no substitute for experienced nursing and
medical staff, whether in a dedicated intensive care unit
or on the general ward
• Clinical observation of the flap is the gold standard ;
performed at hourly intervals for the first 24 hours.
• This can be extended to 1-2 hourly for the next 24 hours,
then 4-hourly for the next 48 hours.
Monitoring
• Signs: color, capillary refill, turgor, and surface temperature
• If capillary refill is not obvious  pinprick testing
• Surface temperature measurement with a surface
temperature probe  difference of 1.8 C between flap
and control sites is 98% sensitive and 75% predictive of
vascular compromise
• Temperatures below 30 C are indicative of flap failure
Monitoring
• Pinprick bleeding
• Temperature monitoring
• Monitor circulation : false-negative in Warm ischemic (without zone II flow)
• A hand-held pencil Doppler probe
• An implantable Doppler probe  esp. for buried flap
• Tissue oxygen
• Trancutaneous oxygen pressure (TcPO2)
• and transcutaneous CO2 pressure
Monitoring
• Near-infrared spectroscopy
• Monitor hemoglobin movement by reflectance of light signals
• Tissue Pressure
• Sensitive for venous occlusion
• Common use in extremity injury / cerebral injury
• Laser doppler flowmeters
• Implantable venous flow coupler monitor higher sensitivity than internal arterial doppler
• Venous thrombosis : common cause of flap failure
Laser-assisted indocyanine green angiography (ICG)
• ICG which tags plasma proteins
• Used to select free flap donor sites and for planning high-risk free flap design
Causes of failing flap
•
•
•
•
Anastomotic failure
Vasospasm
Thrombogenesis
Ischemic tolerance, ischaemia–reperfusion injury, and
no-reflow phenomenon
Sign of vascular compromise
Anastomotic failure
• Principal faults
•
•
•
•
•
tearing
leaking
narrowing of lumen
Through stitching (2wall)
inclusion of the adventitia (prolapse adventitia leads to
thrombus formation)
Vasospasm
• Vasospasm leading thrombosis
• Occurs in 5–10%
• May be seen intraoperatively and up to 72 hours postoperatively
• General factors: low core temperatures, hypotension, and
sympathetic response to pain
• Local factors: trauma to vessel, tight adventitia, myogenic
response to local hemorrhage, vascular disease
• Veins less susceptible to vasospasm than arteries
• But Harder to resolve
Vasospasm
• The most commonly used agents
• papaverine (30 mg/ml)
• opium alkaloid: phosphodiesterase inhibitor -> direct action on smooth muscle
• lidocaine 2-4 %
• vasodilatory mechanism remains unclear
• calcium channel blockers
• nifedipine, verapamil, and nicardipine
• blocking voltage- gated calcium channels in vascular smooth muscle
• mechanical treatment
• gently dilating healthy vessel ends
• Surgical stripping of adventitia
• sympathectomy effect
• mechanical thinning of the vessel walls allows them to dilate more freely
• monitored patient’s temperature(>36), adequate hydration, wound should
not dry
Thrombogenesis
• The risk of thrombosis is greatest within the first 48
hours and decreases to 10% after 72 hours
• The majority of arterial thromboses occur during the
first 24 hours and are related to platelet
aggregation at the anastomotic site
• Venous thrombosis is more often responsible for
flap compromise, presents later, and is related to
the formation of a fibrin clot
Thrombogenesis
• Hypercoagulability
• pregnancy, active cancer, and recent trauma
should be identified preoperatively as far as
possible and warrant thromboprophylaxis
• disorders : activated protein C,
hyperfibrinogenemia, antiphospholipid syndrome
and reactive thrombocytosis should be treated
preoperatively
Thrombogenesis
Heparin
• Unfractionated heparin: irrigate vessels during microvascular
surgery
• Improve patency at high concentrations
• reduces platelet aggregation
• activates antithrombin III (directly deactivating clotting factors II,
IX, X, XI; indirectly factors V and VIII)
• lowers blood viscosity
• vasodilatory properties
• Heparin-induced thrombocytopenia
Thrombogenesis
• important in patients with atherosclerotic or injured vessels, when
vein grafts have been used and with thrombosis of an anastomosis
• LMWH
• inhibit clotting factor Xa
• less of an effect on thrombin inactivation
• may be just as effective in improving patency
• without the risk of hematoma formation
Thrombogenesis
Dextran
• Antithrombolitic effect & volume expander
• No randomized controlled studies have shown a
cause and effect relationship between the use of
dextran and flap loss or prevention of thrombosis
• Has not been shown to be more effective than
other anticoagulants
• Side-effects  anaphylaxis, volume overload,
pulmonary or cerebral edema, platelet dysfunction,
and even acute renal failure
Thrombogenesis
Aspirin
• Inhibits cyclooxygenase and reduces the
breakdown of arachidonic acid to thromboxane,
and prostacyclin
• Low-dose is enough (75 mg/d)
Thrombogenesis
Thrombolytics
•
•
•
•
•
Streptokinase, urokinase, and tissue plasminogen activator
advocated for flaps not responding to standard salvage techniques
may be effective in reversing microvascular thrombosis
significant risk of bleeding in systemic use
can be minimized by local intra-arterial administration of the
thrombolytic and drainage of the venous effluent
• retrospective multi-institutional study even reported no significant
improvement in patency with the use of thrombolytic therapy in
free-flap salvage
Thrombogenesis
Medicinal leeches (Hirudo medicinalis)
• Effectively treat venous congested flaps
• Local anesthetic, vasodilator, and anticoagulant, hirudin 
in saliva
• Hemoglobin should be monitored daily  can be
significant blood loss
• Prophylactic antibiotics against Aeromonas hydrophila from
the leeches’ digestive tract
• Cephalosporin ,fluoroquinolone ,tetracycline , Bactrim
Ischemic tolerance, ischemia–reperfusion injury,
and no-reflow phenomenon
• skin, nerve, bone, muscle, and then intestine being decreasingly
tolerant
• Muscle tolerant 3 hr (warm ischemia)
• Skin & subcutaneous tissue tolerant up to >= 6 hr
• Ischemic time was irrelevant to flap survival provided ischemia
was not prolonged beyond 3 hours or to the point of “noreflow phenomenon.”
• Severe ischemia–reperfusion injury results in irreversible
vasoconstriction, and the resulting inability to reperfuse the flap
despite patent anastomoses  no-reflow phenomenon
Ischemia–reperfusion injury
• result of the buildup of oxygen radicals during the ischemic period
• cause tissue injury, specifically of cellular membranes
• stimulate inflammatory cells (leukocytes, neu- trophils, and platelets,
and other inflammatory mediators and cytokines
• while suppressing protective molecules such as nitric oxide synthase,
prostacyclin, and thromobomodulin.
• no-reflow phenomenon
• ischemia-induced endothelial injury
• leads to cellular swelling, interstitial swelling, exposure of
subendothelial collagen, platelet–leukocyte aggregation, reduction
in blood flow
• if not correct, thrombosis and flap failure.
Management of failed flaps
• Oliva et al. recommend that three issues must be considered when
the initial flap is declared nonviable
• the reasons for failure
• the indications for the free-flap reconstruction
• the current status of the wound (need debridement/reconstruction?)
• If second free flap needed  where possible, do not reuse the
previous recipient vessels as they are likely to be inflamed and friable
Cystalloid volume > 130 ml/kg/24hr independent predictor for medical complication
• -Hct trigger point for transfusion Hct <25 , <30%
• -Blood transfusion in head&neck free flap does not effect flap survival
• -complication not difference
• Suggest transfusion trigger Hb 7 g/dl or Hct 25% for general patient
• Heart disease : Hb 10 g/dl
Resuscitation in free flap
• NIRS (Near-infrared spectroscopy)
• Principle : Absorption rate of near infrared light of Hb&HbO2 differ by wavelength ->calculate
Tissue oxygen saturation
• The actual timing of detection of vascular compromise by NIR
• Venous congestion 0.5-2.3 hr prior to physical finding
• Aterial occlusion 0.75 hr prior to physical finding
• Cut point
• StO2 < 30% or Delta StO2 decrease/h >20% (Sustian for more than 30 min) ->100%
accuracy
• StO2 < 40% or Delta StO2 decrease/h >15% 100% accuracy
• Reginal oxygen saturation index 0.75
• StO2 <15% -> predict flap failure ได ้