Week 8 (Anesthetics, Transplant, Cardiac Life Support) Flashcards
Where do inhaled (volatile) anesthetics work?
Directly activate GABA-A receptor (allow Cl- to come into cell?) and inhibit nicotinic ACh receptors (which are usually excitatory) –> inhibition
Voltage gated ion channels (Na, K, Ca)
G-proteins
Protein kinase C
Anesthetic effects
Explicit memory: amnesia
Consciousness: inhibition perceptive awareness, unconsciousness
Pain response: immobility to pain
Autonomic system: reflex blunting, autonomic depression
Stages of anesthesia
Analgesia
Excitement
Surgical anesthesia
Medullary depression
Minimum alveolar concentration (MAC)
Alveolar concentration (%) of an inhalation agent that produces immobility to noxious stimulation in 50% of subjects (humans: skin incision)
Advantages of MAC: short equilibration time, alveolar concentration represents partial pressure of anesthetic in CNS; consistency for given animal group or between species
Measures potency (increased MAC = decreased potency)
Things that affect MAC
Temperature: MAC decreases with decreasing body temp (approx 2-5% per degree); people who are colder are more likely to go unconscious
Age: MAC is maximal at 6 months of age and gradually decreases with age (MAC for octogenarian is 50% that of infant); gases become more potent as you age
MAC of commonly used gases
NO >100%
Desflurane 6-7%
Sevoflurane 2%
Isoflurane 1.4% (most potent)
Speed of induction: uptake and distribution
Alveolar partial pressures of gas agents govern partial pressure of gas agents in all other parts of body (including brain)
Two factors primarily affect the rate of rise of alveolar partial pressure: alveolar/inspired relationship (FA/FI); uptake by blood
Inspired gas –> alveolar concentration –> uptake
What affects rate of rise of alveolar concentration?
Increased inspired concentration –> increases rate of rise of alveolar conc
Increased uptake by blood –> decreases rate of rise of alveolar conc
Inspired-alveolar relationship
Inspired concentration of the gas
Pulmonary ventilation
Uptake by blood
Decreased solubility increases alveolar concentration more rapidly
Increased CO (pulmonary blood flow) decreases alveolar concentration more rapidly
Alveolar-venous partial pressure difference: dependent upon tissue uptake which effects venous partial pressure; increased venous partial pressure decreases A-V partial pressure difference and increases alveolar partial pressure
Elimination
Occurs as anesthetics are transferred back from brain to alveolar space and exhaled
Less soluble anesthetics eliminated more rapidly
Duration of exposure: since there is accumulation of anesthetic in less perfused tissues (muscle, fat and skin)
Minute ventilation
What increases alveolar partial pressure of gas?
Increased inspired concentration of gas
Increased minute ventilation
Decreased solubility
Decreased CO
Decreased A-V difference (increased venous partial pressure)
Effect of N2O on closed gas spaces
Nitrogen 30x less soluble than NO
NO enters airspaces faster than nitrogen leaves so significant enlargement of airspaces
Airspaces include bowel, inner ear, pneumothoraces, air emboli
Effects of inhaled anesthetics
Pulmonary: decrease or same TV, increase or same RR, decrease or same minute ventilation, increase apneic threshold, increase bronchodilation, increase or same airway irritability
Cardiovascular: decrease BP, decrease myocardial function, decrease (NO increases) SVR, increase (NO decreases) HR, increase or same coronary vasodilation
Brain: decrease metabolic rate, increase cerebral blood flow (increased ICP)
Kidney: decrease GFR
Uterus: except N2O, all others are relaxants (good for delivery, bad after because too much bleeding if uterus doesn’t contract again)
Toxicity: no studies have demonstrated mutagenesis, teratogenesis, and carcinogenesis with modern anesthetics
IV anesthetics
Rapid induction of anesthesia
Continuous sedation with infusion
Ex: propofol, ketamine, etomidate, dexmedetomidine
One compartment model
Drug administration –> V1 central compartment –> elimination
Three compartment model
Drug administration –> V1 central –> V2 rapid equilibrating compartment or V3 slower equilibrating compartment –> elimination or Ve effect site to elimination
Propofol
Most frequently used IV anesthetic
Administered as bolus (induction) or infusion (maintenance)
Metabolized in liver and excreted in kidney, and 20% excreted in lungs
Abuse potential (“milk of amnesia”)
Initial distribution half-life = 1-8 minutes
Slow distribution half-life = 30-60 minutes
Elimination half-life = 4-23 hours
Primary effect is hypnosis (sedation by potentialting GABA-induced Cl by acting on GABA-A); pleasure seeking by increase DA in nucleus accumbens; anti-emetic by decreasing 5HT in area postrema
Minimal analgesia
Decrease ICP, decrease CMRO2
Decrease BP, O2 supply and demand
No predictable change in HR
Bolus decreases RR and TV and can cause apnea (exaggerated by narcotics)
Infusion causes decrease TV and rate with overall decrease in minute ventilation (exaggerated by narcotics)
Induces bronchodilation
Other effects: euphoromimetic, pain on injection, sepsis/infection, anaphylaxis
Ketamine (PCP)
Glutamic acid inhibitor at NMDA receptor
Metabolized by liver
Slow distribution half-life = 11-16 min
Elimination half life = 2-3 hours
Unconsciousness and analgesia
Dissociative anesthesia: patients appear to be in cataleptic state with eyes open and many reflexes intact but profound analgesia and amnesia
Some opioid mu receptor activity
Increase ICP, cerebral metabolism, CBF
Increase BP, HR, CO, O2 demand and work, SVR, PVR (central mechanism that enhances SNS to release NE)
No effect on central respiratory drive
Bronchodilator
Increased salivation with possible airway obstruction in children
No pain on injection
Undesirable psychological reactions during awakening (vivid dreaming, extracorporeal experiences and illusions), associated with excitement, confusion, euphoria and/or fear, attenuated by benzos
Etomidate
Imidazole derivative
Half life 3 minute initial redistribution, 29 minute slow distribution half life, 2.9-5.3 hour elimination
Cleared by liver
Hypnosis (GABA agnoist)
After bolus, CMRO2 decreases by 45%, CBF decreases by 34%, net increase in cerebral O2 supply-demand ratio
Reduction in ICP
EEG similar to barbiturates, ultimately burst suppression; increases EEG activity in epileptogenic foci
Minimal cardiovascular effects (and no effect on SNS or baroreceptors)
Respiratory effects: minimal effect on ventilation, ventilatory response to CO2 depressed (leads to brief periods of apnea), doesn’t release histamine, mild pulmonary vasorelaxant effects
Potetial problems: mild decrease in cortisol (not likely relevant), pain on injection, N/V, myoclonus and hiccups
Uses: bolus to induce general anesthesia; useful in pts with compromised CV system; useful in neurosurgical procedures because decreased ICP (?) and good cerebral O2 supply/demand and good CV stability
Summary of clinical uses for IV anesthetics
Propofol: short cases, outpatient cases, neurosurgical cases, ophthalmology cases, other cases involving patients with reasonably normal myocardial function (most common agent)
Ketamine: trauma cases with significant hypovolemia/shock, pediatric cases (especially congenital heart with right to left shunt)
Etomidate: cardiac and vascular cases, heart and lung transplant cases, patients with significantly depressed myocardial function, also can be used in neurosurgical cases
Dexmedetomidine
Alpha2 agonist but highly selective (more than clonidine)
Sleep-like hypnosis
Minimal effect on respiration
Decreases HR, BP, CO
Becoming increasingly popular to use as infusion in intubated pts in ICU
Other IV anesthetics
Barbiturates
Benzodiazepines
Narcotics
Local anesthetic
Drugs that produce reversible, conduction blockade of impulses along central and peripheral nervous pathways after regional anesthesia
Cocaine as topical anesthetic
Cocaine is vasoconstrictive (less bleeding in surgical area)
ENT uses cocaine for endoscopy of nose/sinuses (can anesthetize mucous membrane)
Only ester that is metabolized in the liver
Procaine
Local anesthetic
Disadvantages are that it has short duration, systemic toxicity, allergic reactions
Lidocaine
Most widely used cocaine derivative
Inhibits membrane depolarization by blocking conductance of Na+ into cell (reversibly binds and inactivates Na+ channels)
Blocks conduction in peripheral nerves
Action ends when concentration falls below critical minimal level
Rapid onset of action, 2 hr duration (4 hr with epinephrine)
Different nerve fibers and which ones are affected by local anesthetics
Small C fibers (unmyelinated) and small/medium sized A delta fibers (myelinated) are more sensitive to action of local anesthetics than larger fibers, so patients may be able to feel sensations such as pressure and vibration but not pain
A alpha: muscle spindle
A beta: muscle spindle, touch
A gamma: touch, pressure
A delta: pain
B: preganglionic autonomic
C: pain
Chemical structure of local anesthetics
Amine end is hydrophilic
Aromatic end is lipophilic
Linked by intermediate chain: amino amides have amide link and amino esters have ester link
Amino amides
Amides have “i” in first part of word
Lidocaine
Mepivacaine
Prilocaine
Bupivacaine
Etidocaine
Dibucaine
Metabolized by liver and allergic reaction less likely
Amino esters
Esters have no “i” in first part of word
Tetracaine
Procaine
Chloroprocaine
Cocaine
Benzocaine
Metabolized by pseudocholinesterase (a plasma enzyme) and more likely to have allergic reaction
What determines physiologic activity of local anesthetics?
Lipid solubility determines potency (increased lipid solubility leads to faster blockade of Na+ channels)
Diffusibility influences speed of action
Protein binding related to duration of action
Percent ionization at physiologic pH: nonionized form diffuses across nerve membrane so means faster onset of action; decreased pH shifts equilibrium toward ionized form which delays onset of action (slower onset of action and less efficetiveness in presence of inflammation which has acidic environment)
Vasodilating properties
Adjuvants to local anesthetics
Bicarbonate: to speed onset of action by increasing pH
Epinephrine: vasoconstrictor so washout of anesthetic slower so longer duration of local anesthetic
Opioids: analgesic so can use less local anesthetic, less motor blockade but same sensory blockade
Hyaluronidase: enzyme that breaks collagen so better tissue penetration of local anesthetic; only used in ophtho cases for retrobulbar block
Metabolism of local anesthetics
Esters metabolized by plasma enzyme pseudocholinesterase and excreted in urine
Exception is cocaine which undergoes metabolism in the liver
PABA is an allergen and a metabolite of hydrolysis by pseudocholinesterase (?)
Amides metabolized in liver and should be used with caution in pts with liver disease
Adverse effects of local anesthetics
Due to the anesthetic solution:
Systemic toxicity (cardiovascular and CNS)
Allergy (hypersensitivity reaction; hives, swelling)
Neurotoxicity
Tissue irritation
Cardiovascular toxicity: decrease depol of cardiac tissue, decrease conduction velocity; vasodilation leading to hypotension; negative inotropic effect leading to bradycardia, v-fib, asystole
CNS toxicity: light headedness, tinnitus, circumoral numbness, metallic taste, double vision, drowsiness, slurred speech, nystagmus, seizures leading to hypoxia, acidosis, hyperkalemia, respiratory arest
Progression of symptoms in lidocaine toxicity
Numbness of tongue
Lightneadedness
Visual disturbance
Muscular twitching
Unconsciousness
Convulsions
Coma
Respiratory arrest
CVS depression
Special toxicity considerations
Benzocaine: methemoglobinemia
2-chloroprocaine: back pain when large doses used and is related to EDTA in preparation
Bupivacaine: CVS toxicity at serum concentration slightly above seizure threshold, cardiac arrest that is resistant to resuscitation (pt needs to be on bypass until bupivacaine wears off)
Techniques for regional anesthesia
Topical anesthesia
Local infiltration
IV regional anesthesia: Bier block
Peripheral nerve block: brachial plexus, median nerve
Spinal anesthesia
Epidural anesthesia
Caudal block
NTs used in peripheral nervous system
Somatic nervous system: Ach acts on nicotinic receptors of motor neurons of skeletal muscle
ANS sympathetic nervous system (thoracolumbar region with ganglia near spinal cord): Ach is preganglionic but NE is primary postganglionic (Epi for adrenal glands and Ach for sweat and salivary glands though)
ANS parasympathetic nervous system (cervicosacral region with ganglia near innervated tissue): Ach only!
Ach is the NT for what?
Ach is NT for:
All preganglionic parasymp and symp ANS fibers
All postganglionic parasymp ANS fibers
Postganglionic symp fibers to sweat and salivary glands
All somatic motor neurons released at NMJ
Nicotinic Ach receptor (nAchR)
Receptor is ligand-gated ion channel
2 Ach molecules required to bind 2 alpha subunits to open Na/K ion channel
Muscarinic Ach receptor (mAchR)
G protein coupled receptor
Ach is ligand
Nicotinic vs muscarinic receptors
Nicotinic receptors use ion gated mechanism for signaling; sufficient ligands cause ion channel to open; diffusion of Na and K across receptor causes depolarization, the end-plate potential, that opens voltage-gated Na+ channels which allows for firing of AP and potentially muscular contraction; primary receptors of autonomic ganglia and sole Ach receptors at NMJ
Muscarinic receptors use intracellular G proteins as signaling mechanism; ligand (Ach) binds receptor which has 7 transmembrane regions; receptor bound to intracellular G proteins which activate other ionic channels via second messenger cascade; found at some autonomic ganglia and effector organs
Botulinum toxin
Degrades synaptobrevin (SNARE protein) preventing Ach containing vesicles from fusing with presynaptic plasma membrane –> blockade of Ach release –> flaccidity (“floppy baby”)
In case of poisoning, treatment is antitoxin and supportive care (mechanical ventilation)
Medical therapies include treatment of migraines, spasticity, cosmetics, etc
Summary of Ach at the NMJ
Ach released from presynaptic nerve terminal into synaptic cleft after nerve impulse
Ach then binds 2 alpha subunits of nAchR opening the ion channel to Na+ and K+
When sufficient nAchRs are activated, transmembrane potential increases from -90 mv to -45 mv and AP is propagated over skeletal muscle surface causing contraction
Use of neuromuscular blockade in anesthesiology
NMB used daily by anesthesiologists to facilitate endotracheal intubation, provide muscle relaxation as needed for intraabdominal, orthopedic, laparoscopic and delicate surgeries
Succinylcholine
Depolarizing neuromuscular blocker
Structurally similar to Ach (competitive agonist) and binds 2 alpha subunits of nicotinic receptor to open the channel
Rapid (<60 sec) depolarization of muscle cells causes fasciculations followed by flaccid paralysis
Use when rapid and/or brief paralysis desired (rapid endotracheal intubation for patients at risk for pulmonary aspiration, for pts with potentially difficult ET intubation, relaxation for very short procedures such as direct larygoscopy/biopsy)
Remains bound for several minutes because NOT broken down by acetylcholinesterase; diffuses away from motor end plate and quickly degraded into acetic acid and choline by pseudocholinesterase (which is NOT found at NMJ)
Muscle function usually returns after 5-10 min
Side effects: hyperkalemia due to depolarization (more in pts with recent burns, renal failure, neuro/muscular disorders), myalgias, increased ICP, intragastric pressure, ophthalmic pressure; may cause prolonged paralysis if pt has atypical pseudocholinesterase; malignant hyperthermia
Nondepolarizing neuromuscular blockers (NDMBs)
Everything else other than succinylcholine!!
Quarternary ammonium compounds with structures similar to Ach
Bind selective alpha subunits of nicotinic receptors
Bulky molecules bind nAchR and act as competitive antagonists to prevent depolarization
Reversal due to slow release into NMJ and then hepatic/biliary and/or renal metabolism
Two classes of NDMBs
Benzylisoquinolines: curare derivatives including d-tubocurare, atracurium, cisatracurium
Aminosteroids: pancuronium, vecuronium, rocuronium
When do you see the effect of NDMBs?
No evidence of NM blockade when even 70% of nAchR are blocked!
Once 80-90% of nAchRs are blocked then NM transmission fails
This margin of safety essential in modern anesthesia and is basis for monitoring NM blockade in OR
Short acting NDMBs
Mivacurium: duration 12-20 min; like succinylcholine metabolized by pseudocholinesterase; but discontinued by manufacturer
Intermediate acting NDMBs
Cisatracurium: duration 40-75 min; metabolized by Hofman elimination (pH and temp dependent enzymatic degradation NOT organ dependent; good for pts with liver and kidney disease)
Vecuronium: duration 45-90 min; primarily hepatic/biliary but some renal excretion
Rocuronium: like succinylcholine, rapid onset makes appropriate for rapid intubation; duration 35-75 min; primarily hepatic/biliary but some renal excretion
Long-acting NDMBs
Pancuronium: duration 60-120 min; atypically increases HR by vagal antagonism at cardiac receptors; long-acting NDMBs with primarily renal excretion
Side effects of NDMBs
Histamine release by atracurium, pancuronium, mivacurium (and morphine!) can cause bronchospasm, flushing, peripheral vasodilation (avoid in severe asthmatics, septic and other susceptible pts)
Allergic reactions can cause anaphylaxis
What happens with NDMBs when surgery ends?
Problem: residual weakness at end of surgery may prevent adequate spontaneous ventilation
Solution: reverse the paralysis by increasing amount of Ach at NMJ (neostigmine) to competitively beat out NDMB and cause muscle contractions
Reversal of NM blockade
AchEIs reversibly bind and inactivate AchE in NM junction
Used to increase level of Ach in NMJ to compete with NDMBs for binding sites, thereby reversing NDMB paralysis
Problem with NM blockade reversal
Ach is also increased at MUSCARINIC receptors!
SLUDGE
Antimuscarinic (atropine) agents must be used to block effects of Ach and avoid cholinergic effects!
Neostigmine
Reversibly inhibits AchE to allow Ach to remain elevated to stimulate nicotinic and muscarinic receptors
Most commonly used reversal agent in OR
Weak nAchR agonist so excess dosing can itself cause weakness
Also inhibits pseudocholinesterase activity, so NEVER give succinylcholine after administering neostigmine
Edrophonium
Reversible AchEI
Rapid onset only 1-2 min, lasts >1hr only at higher doses
Less than 10% as potent as neostignime
Used to diagnose myasthenia gravis: if strength improves after giving edrophonium it means Ach levels got high enough to overcome Ach receptor antibodies, leading to resumption of stimulation at NMJ
Pyridiostigmine
Reversible AchEI
20% as potent at neostigmine
Limited inhibition of pseudocholinesterase
Used to treat myasthenia gravis
Physostigmine (“antilirium”)
Tertiary amine
Only AchEI that crosses BBB
Used to treat CNS anticholinergic toxicity and for antagonism of volatile anesthetic effects especially in patients with Alzheimer’s disease
Irreversible AchEIs
Organophosphates
Form very stable bonds to enzyme AchE –> increased Ach
Used in ophthalmology to induce miosis and thereby decrease intraocular pressure
Key ingredient in pesticides
Acute treatment of organophosphate poisoning is with anticholinergic agent atropine but definitive treatment is pralidoxime (must be given before “aging” occurs though)
What happens even if you give an appropriate dose of neostigmine for reversal of NM blockade?
Inhibition of AchE causes increased Ach which causes increased muscle contractility but ALSO cholinergic crisis (SLUDGE = salivation, lacrimation, urination, defecation, GI upset/hypermotility, emesis) and bradycardia
Excessive dosing can exacerbate weakness
Preventing adverse reaction to AchEIs
Pretreat with an anticholinergic agent to act at muscarinic receptors
Ex: glycopyrrolate, atropine
Anticholinergics/antimuscarinics
Atropine: fast onset, shorter duration, crosses BBB, used in tx of bradycardia and as part of ACLS
Glycopyrrolate: intermediate onset, longer duration, does NOT cross BBB, may also be used to counteract bradycardia (induced by surgical stimulation of parasymp nervous system)
Pralidoxime
Antidote for AchEIs because reactivates inhibited AchE
Treat organophosphate exposure
Helps prevent phosphorylation by organophosphate and helps reactivate AchE
Also used to treat patients exposed to nerve gas or with OD of pyridostigmine (cholinergic crisis) in myasthenia gravis
Reversal agent/anticholinergic combinations in anesthesia
Safe and effective reversal is based on speed of onset and duration of action fo drugs used
Neostigmine/glycopyrrolate
Edrophonium/atropine
Pyridiostigmine/glycopyrrolate
Physostigmine/not applicable
Sugammadex
Novel NMB reversal agent
Negatively charged cyclodextrin molecule that reverses NMB by electrostatically binding aminosteroid nondepolarizing agents
Most avidly encapsulates Rocuronium, less avidly binds vecuronium and no binding of benzylisoquinolines
Binding creates concentration gradient favoring release of rocuronium fron nAchR
Equal or faster recovery time after rocuronium compared with succinylcholine
Overcomes problem of inability to achieve timely/complete NMB reversal and complications by relying on Ach
Why are living donor transplants better than deceased donor transplants?
Because living donor kidneys are healthier–they’re alive!
NOT because of matching
Benefits of kidney transplant
Transplant doubles anticipated lifespan of patient waiting for transplant
Life-prolonging, and quality-of-life-enhancing
Causes of death of people waiting for kidney transplant
Diabetes mellitus
glomerulonephritis
Hypertension
Other
Annual death rate overall is 6.3%
Types of transplant rejection
Hyperacute rejection (antibody-mediated)
Acute rejection (cell-mediated, antibody-mediated, vascular rejection)
Chronic rejection
Chronic allograft nephropathy (CAN)
3 signal hypothesis of how body responds to antigen
Signal 1: APC presents antigen to T cell receptor (“kiss”)
Signal 2: Costimulation by B7 on APC to CD28 on T cell (“hug”); after 2 signals, calcineurin (phosphatase enzyme) dephosphorylates NFAT so NFAT can now get into the nucleus and cause transcription of IL-2 and CD25 –>
Signal 3: self-proliferation signal
Cyclosporin and tacrolimus
Calcineurin inhibitors
Block the dephosphorylation of NFAT so NFAT cannot get into the nucleus to cause transcription of IL-2 and CD25 –> no signal 3 to cause proliferation of T cell
Slow down process of responding to foreign antigen
Note: don’t have to tweak immune system THAT much, just cut calcineurin activity by 50% and this is enough
Belatacept
CTLA-4 Ig
Like abatacept in RA
Blocks costimulatory molecule (B7) from interacting with counterpart on T cell
Basiliximab
Mab to CD25 receptor (the receptor for IL-2) on T cells
Blocks signal 3 so T cell cannot proliferate
Sirolimus/everolimus
AKA Rapamycin
Blocks mTOR so cannot do cell division
Syndromes of calcineurin inhibitor toxicity
Prolonged DGF
Acute reversible decrease in GFR (due to vasoconstriction caused by calcineurin)
Post-transplant TTP
Chronic CI toxicity
Electrolyte disturbance
Why do non-renal transplant recipients develop CKD?
Because any transplant causes fibrosis in some way
20% of non-renal transplant recipients become candidates for renal transplant
Indications for heart transplant
Intractable angina
Refractory heart failure
Uncontrolled ventricular arrhythmias
Medications as alternative to heart transplant to improve survival
Baseline 5-year survival is 40% but with these meds, can raise that to 75%
ACEI
Beta blocker
Aldosterone antagonist
ICD
Absolute and relative contraindications to heart transplant
Absolute contraindications:
Active malignancy
Active infection
Obesity with BMI > 35
Active substance abuse
Noncompliance
Lack of social support
Relative contraindication:
Diabetes with end-organ dz
Pulmonary HTN
Age > 70
Renal failure
Cerebrovascular/peripheral vascular disease
Cirrhosis
Pulmonary disease
Status waiting for a heart transplant
Status 1A (days): PA cath + 2 drips; VAD < 30d; IABP or ventilator, exceptions
Status 1B (weeks): 1 inotrope; VAD > 30d
Status 2 (months): everyone else
Longer wait time for larger people and blood type O because just harder to find
Mortality after heart transplant
Biggest mortality in first year is infection and rejection (only 10% of pts)
After that, conditional half life is 15 years
Cardiac allograft vasculopathy and malignancy more common in year 2 and beyond
Significance of the fact that the transplanted heart is denervated
No afferents so no angina
No efferents so no vaual input so higher resting HR and rely on circulating epi and NE from adrenal during exercise
More exaggerated orthostatic response because loss of feedback regulation (baroreceptor reflex, RAAS)
Increased receptor density so more sensitive to circulating epi, NE
Medications that have no effect or exaggerated effect in heart transplant
No effect: atropine, digoxin (because no vagus nerve)
Exaggerated effect: adenosine, beta agonists, beta blockers (because more alpha and beta receptors)
Endomyocardial biopsy for rejection surveillance
Looking for cellular and humoral rejection
Only care about moderate and severe to treat
Treatment of rejection depends on whether pt is asymptomatic, reduced EF or in heart failure/shock
Transplant coronary artery disease
Asymptomatic (denervation), fagitue, reduced EF
Panvascular disease, distal pruning
Rapid progression
Concentric lesions
Generally lipid poor, fibrointimal proliferation
Management of transplant coronary artery disease
Diagnosis: surveillance angiograms, IVUS (not standard)
Prevention: aspirin, pravastatin (doesn’t interact with tacrolimus), vitamin C and E, sirolimus
Treatment: PCI but doesn’t work that well and pts usually need second transplant (TCAD is most common indication for second transplant)
How long do heart transplants usually last?
10-15 years
Indications for lung transplant
CF
Idiopathic pulmonary fibrosis (IPF)
COPD
Alpha 1 antitrypsin deficiency
PPH
5 year survival rate for lung transplant
Should we give induction immunosuppression at time of lung transplant?
No evidence that it makes any difference in terms of survival, but we do it at UCLA anyway
Post lung transplant morbidity
Infection biggest problem in first 30 days (lung exposed to outside environment…)
Hypertension
Renal dysfunction
Hyperlipidemia
Diabetes
Bronchiolitis obliterans syndrome (chronic rejection after transplant; is progressive obstructive just like emphysema and is biggest cause of death more than 1 year after transplant; at 5 years, 50% of pts have this)
Skin cancer (squamous cell carcinoma) is problem!
