Organ Transplant

Question 1

What are the recommended cold ischemia time for heart/lungs, livers, kidneys?

Answer 1

• Cold ischemia times (Barash), unos.org gives shorter times: preferably not as long (cold ischemia starts when arterial supply gets clamped)
  
  • less than 6 hours for heart or lung grafts
  • 12 to 24 hours for livers
  • up to 72 hours for kidneys

Question 2

What are some methods that increase the donor pool?

Answer 2

• Donation after cardiac death donors (DCD) previously called “non-beating heart”
  
  • as opposed to brain dead
• Acceptance of “marginal donors”
  
  • generally get paired with marginal recipients
  • older people with comorbidities
• Paired kidney donations (kidney swaps)
• Some of the increase in deceased donation is d/t increased usage of donors w/ a broader set of medical criteria than considered in past.
• Nearly 20% of donors in 2018 donated after circulatory death as opposed to brain death.
• 9% of deceased donor kidney transplants involved organs with a kidney donor profile index (KDPI) score of 86 or higher, which may function less time compared to low KDPI kidney offers but may also shorten the waiting time for transplant candidates.
• Other donor characteristics setting all-time records in 2018 included age of 50 or older and/or being identified as having increased risk for blood-borne disease

Question 3

What is the organ procurement and transplantation network? united network for organ sharing?

Answer 3

• Organ Procurement and Transplantation Network [OPTN]
  
  • Established by Congress in 1984
  • Facilitates organ matching/allocation process
  • Collects and manages data about organ donation and transplantation
  • Professional and public education
• United Network for Organ Sharing [UNOS]-administers the OPTN under contract with Health Resources & Services Admin of the U.S. Dept. of Health & Human Services
  
  • Develop policy
  • Monitor/Enforce processes of OPTN
  • Maintain OPTN membership and review applications
  • 2006: DonorNet- how they match donors to recipients
  • Electronic resource for matching and distribution of organs around the United States
  • Regional databases based on feasibility of achieving optimal cold ischemia times

Question 4

What was the medication that changed survival rates in transplants?

Answer 4

cyclosporine

Question 5

What are some wait time factors for the organ recipient?

Answer 5

• blood type; always confirm ABO compatibility of donor and recipient prior to surgery (HLA and ABO compatibility)
• tissue type
  
  • not as many heart/lung vs kidney
• height and weight of transplant candidate
  
  • ie lungs need to be optimally sized for best outcomes
• size of donated organ
• medical urgency
• time on the waiting list (not as important now—look more at regional and survivability)
• the distance between the donor’s hospital and the potential donor organ
• how many donors there are in the local area over a period of time (trauma center versus not, more organs high trauma area)
• the transplant center’s criteria for accepting organ offers – some only get high quality and others are volume-based
• need social, psychosocial support. Cant charge for organ but the rest cost $. Stay at hotel nearby for up to 6 mos. $$. Can be on multiple regional lists.
• Right to self-determination w/ donors, beneficence, maleficence, and equity. Huge ethical criteria.
• Use of marginal donors has expanded pool- ”marginal donor status” hepatitis, LV dysfunction, CAD, advanced age, DCD
• Marginal donors are used for patients who do not meet standard criteria
• 16% DCD in 2015
• DCD kidneys do well although longer time to graft function; DCD livers have poorer survival

Question 6

Major indication for transplant? (don’t think she’ll actually test on this)

Answer 6

• Lung
  
  • # 1 idiopathic pulmonary fibrsois
  • Obstructive lung disease
• Heart
  
  • CMP
• Intestinal
  
  • primarily in kids (short gut syndrome)
• Pancreas
  
  • T1DM

Question 7

What are some considerations before transplant after brain death?

What patient criteria need to be met before clinical tests for brain death can be performed?

Answer 7

• Definitions will very state to state
  
  • Cessation of cerebral and brain stem function
    
    • death from a physiologic standpoint, does not mean that the patient will die a cardiac death
• Physicians involved in the transplant process may not be involved in the declaratory process
• First- potentially reversible causes are ruled out
  
  • Hypothermia ( _>_36 C), hypotension ( > SBP 100 mmHg) even w/ pressors, drugs, toxins
  • Achieve normal core temperature.
    
    • Prior use of hypothermia (e.g., after cardiopulmonary resuscitation for cardiac arrest) may delay drug metabolism.
    • In most pts, warming blanket needed to raise body temp and maintain a normal or near-normal temperature (36°C)
  • Exclude presence of CNS-depressant drug effect by history, drug screen, or plasma levels below the therapeutic range.
  • Legal alcohol limit for driving (BAC 0.08%) is a practical threshold below which brain death exam could reasonably proceed.
  • No recent admin or continued presence of NMBDs (presence of a train of 4 twitches w/ maximal ulnar nerve stimulation).
  • There should be no severe electrolyte, acid-base, or endocrine disturbance
• Clinical exams completed once above has been met
  
  • Apnea test
• Validated with diagnostics
  
  • EEG, transcranial doppler, angiography

Question 8

Clinical exams for brain stem reflexes?

Answer 8

• Brainstem Reflexes: combination of tests, not just ONE!
  
  • Absence of pupillary response to a bright light is documented in both eyes
  • Absence of ocular movements using oculocephalic testing and oculovestibular reflex testing
    
    • Oculocephalic reflex: Movement of eyes should be absent during 1 min of observation. Both sides tested, w/ an interval of several mins.
  • Absence of corneal reflex— many don’t have if wear contacts
    
    • ​Corneal reflex: Absent corneal reflex is demonstrated by touching the cornea with a piece of tissue paper, a cotton swab, or squirts of water. No eyelid movement should be seen.
  • Absence of facial muscle movement to noxious stimulus
  • Absence of the pharyngeal and tracheal reflexes
    
    • pharyngeal or gag reflex is tested after stimulation of the posterior pharynx with a tongue blade or suction device.
    • tracheal reflex is most reliably tested by examining the cough response to tracheal suctioning. The catheter should be inserted into the trachea and advanced to the level of the carina followed by 1 or 2 suctioning passes
• Brain death is not perfect: bodies of some patients who meet all criteria for brain death can survive for many years with all bodily functions intact except for consciousness and brain stem reflexes
• • *

Question 9

What is the apnea test?

Answer 9

• 100% FiO2 for 10 minutes (preoxygenate)
• Normalized PaCO2
  
  • Confirmed by ABG
  • T-piece: 7-10 minutes after disconnecting vent (want no ventilatory effort for 10 min)
  • Repeat ABG
• PaCO2 >60mmHg
• Absence of spontaneous ventilation

if become hypotensive, if start to decompensate, they are placed back on vent and then retest

Question 10

What are some aberrations that occur after brain death?

Answer 10

• Hemodynamic instability, wide swings in hormone levels, systemic inflammation, and oxidant stress
• Just after brain death = adrenergic surges= ischemia and ischemia-reperfusion injuries
  
  • Transient period of hypotension with increased cardiac index and tissue perfusion
    
    • precedes the autonomic storm associated with herniation of the brain
  • bradycardia after brain herniation is often unresponsive to atropine
  • catecholamine storm is often followed quickly by pituitary failure
• Pituitary failure: hormone therapy; specifics vary widely
  
  • triiodothyronine (thyroid hormone infusions)—**helps w/ response to pressors
  • Desmopressin to maintain SVR at 800 to 1,200 dyne/s/cm5 (and for DI secondary to loss of pituitary function) good HD status
  • Low-dose vasopressin also can be used for DI and to reduce catecholamine requirements- get ADH and pressor effect, w/ hypotensive
  • Methylprednisolone (vs hydrocortisone)
• High doses of catecholamines avoided. If use pressor—use dopamine w/ as low of a rate as possible
• Insulin infusion to maintain blood glucose at 120 to 180 mg/dL to maintain function of all organs
• Coagulopathies may require correction

Question 11

What is uncontrolled DCD? Controlled DCD?

Answer 11

Uncontrolled DCD refers to organ retrieval after a cardiac arrest that is unexpected and from which the patient cannot or should not be resuscitated (not brain dead)

Controlled DCD: planned withdrawal of life-sustaining treatments that have been considered to be of no overall benefit to a critically ill patient

• The patient is brought to the OR, life support is withdrawn – fam had time to say goodbye and going to OR is the finale vs in ICU
  
  • Wait up to 1 hour without ventilation or other support
  • Patient is observed for 2-5 minutes to ensure that the heart does not start beating again spontaneously
• If there continues to be no circulation for 2–5 minutes, the physician pronounces the patient dead.
• At this point, the transplant team enters the operating room and removes organs, usually the kidneys and liver, from the now dead patient.

Question 12

What are some criteria for controlled DCD?

Answer 12

• Death likely within 1 hour of withdrawing support per ICU team; family willing to discuss withdrawal of care
• Characteristics
  
  • Ventilator dependent for respiratory insufficiency: apneic or severe hypopneic; tachypnea ≥ 30 breaths /min after DC ventilator
  • Dependent on mechanical circulatory support (LVAD; RVAD; V-A ECMO; Pacemaker w/ HR < 30 beats per minute without support)
  • Severe disruption in oxygenation: PEEP≥ 10 and SaO2 ≤ 92%; FiO2 ≥ .50 and SaO2 ≤ 92%; V-V ECMO requirement
  • Dependent upon pharmacologic circulatory assist: Norepinephrine, epinephrine, or phenylephrine ≥ 0.2 ug/kg/min; Dopamine ≥ 15 ug/kg/min
  • IABP and inotropic support: IABP 1:1 and dobutamine or dopamine ≥10 ug/kg /min and CI ≤ 2.2 L/min/M2; IABP 1:1 & CI ≤ 1.5 L/min/M2
• Circulation and respiration absent for a minimum of 2 minutes before procurement started

Question 13

Donor anesthesia setup for OR?

Answer 13

• Goal: optimizing organ perfusion and oxygenation
• Pressors on hand (vasopressin, epi, norepi, ephedrine, neo, dopamine, dobutamine)
  
  • Response to pressors can be variable and difficult to manage
  • Mainstay for BP—-FLUIDS (more for kidneys, less for lungs)—know goals of transplant team
• Lung protective ventilatory strategies; transport to OR with PEEP valve; may need ICU vent
  
  • don’t disconnect vent: clamp ETT; disconnect and attach to bag w/ high PEEP valve and then un-clamp. if disconnected, de-recruit lungs
• Thromboprophylaxis—high risk for blood clots. Hep right before they take organs .
• Maintain normothermia (warming vs. cooling mechanisms). High fevers w/ loss of brainstem reflexes. Once die or DCD- get v cold!
• Available: draw bunch of labs HLA typing, serology, virology of pt
  
  • As directed by procurement team: Steroids, N-acetylcysteine, Povidone-Iodine (per NGT); prostaglandin E₁
  • Broad spectrum antibiotics, mannitol, loop diuretics, heparin (usually 30-50,000 units of heparin)
• • Procedure about 1-5hours (sterile): anesthesia present to support organ systems until prox aorta is clamped: once aorta clamped and cooling has started= anesthesia services no longer needed (usually remove PA cath if take the heart), want to d/c vent, fluids off, monitors
• All about communication w/ the team
  
  • Want Fi02 100% and PEEP to maintain oxygen sats
  • >100 SBP
  • UO 2ml/kg/hr (want 4-6 L of crystalloid and 2 L albumin available for resuscitation)
  • Don’t want a lot of vasopressors usually. When use dopamine- want <20mcg/kg/min
  • T4 usually running- improves HD stability in BD pts- converts from anaerobic to aerobic metabolism, controls acidosis, and controls cardiac contractility (dec pt’s need for pressors)

Question 14

Hemodynamic/ lab goals for donor OR?

Control of spinal reflexes?

Answer 14

• CVP monitoring (maintain 6-12 mmHg)
  
  • Depends on organs procured
  • Higher for kidneys and lower for lungs (fluid admin a/w acute graft failure for lung transplants).every addtl L given during procurement increases # of pts w/ acute graft failure
• Na+ <155
• PaCO2 30-35 mmHg
• Spinal reflexes may be intact and NMB’s may be needed
• Volatile anesthetics may help to blunt spinal reflexes, reduce the adrenergic storm (DCD will have storm after asystole for 2-5min) and provide some ischemic preconditioning to the vital organs (controversial 0.4 Iso—some give, some don’t)
• Opioids will also help with reduction in response to stimulation- most people don’t give opioids
• May need the ICU vent if complex vent settings being used
• Diuretics may be given prior to lung procurement

Question 15

Potential complications during organ harvest?

Answer 15

1. Hypoxemia (atelectasis, pulmonary edema, aspiration, or pneumonia)
   
   • FiO₂ and minute ventilation to maintain a PaO₂ ≤100 mm Hg, PaCO₂ = ~35, & pH WNL, SBP >100, UO:2mL/kg/hr
   • Follow ABG every 30 to 60 minutes
   • Avoid High PEEP to preserve cardiac output and avoid barotrauma
   • Avoid High FiO₂ in potential lung donors to minimize possible oxygen toxicity. Most tx can use 100% tho
2. Unable to regulate temperature: actively warm
3. Hypertension transiently accompanies brain death and can be dramatic
   
   • Reflex hypertensive responses to surgical stimulation may occur
   • Tx with Short-acting agents such as nitroprusside or esmolol should be used bc acute hypotension & pituitary failure soon
4. Hypotension follows due to hypovolemia & poor vasomotor control
   
   • Tx with crystalloid, colloid solutions, and blood products (6 L of crystalloid and 2 L of albumin)
   • Keep hct >30%
   • Use pressors PRN—try to avoid, but as needed (dopamine is pressor of choice)
5. Dysrhythmias (due to electrolyte imbalance, hypothermia, increased ICP, hypoxemia and acidosis, and derangement of brainstem cardiovascular control centers)
   
   • Antiarrhythmics (use like normal. V tach- lido or amiodarone) – esmolol, pacing, replacing lytes
   • Bradycardia resistant to atropine—may need pressors (epi available); have pacing available
6. Polyuria(due to volume overload, osmotic diuresis, or DI from derangement of the HPA) common
   
   • Maintain IV infusion of vasopressin or desmopressin may be titrated to treat severe diabetes insipidus (patients receiving vasopressin need fewer pressors)
   • discontinue these infusions 1 hour before aortic cross-clamping to minimize the risk of ischemic injury (esp w/heart and lungs)
   • need fewer pressors w/ vaso instead of other pressors
7. O​liguria
   
   • Use volume; good diuresis will be preferred if kidneys taken
   • Use pressors
   • Fluid & pressors not working? mannitol and/or furosemide

Question 16

Care for the living kidney donor?

Answer 16

• Healthy; no renal disease; no history of proteinuria or renal stones
• Most often laparoscopic (hand assisted)
  
  • small number of these robotically assisted (higher complication rate)
  • rarely done open - position: lateral with bed flexed; high rate chronic pain post-op (up to 1/3)
• 2.4% of kidney donors experience anesthetic/surgical complications (unacceptably high!) 2.4/100 ppl
• Good ERAS candidate: pre-hydration CHO load (carb load); TAP blocks; multi-modal – preemptive analgesia, fluid mgmt., avoid ops
• Insufflation decreases renal blood flow: compensated with fluids to prevent pre-renal injury & mt renal perfusion
• Nitrous oxide is contraindicated (surgeon visualization impaired) bowel distention makes more diff to see retroperitoneal structures
• Not common to place CVL; CVP unreliable with lap retrieval in lateral position – 2 IV bc hard to place another w/ lateral
• Extubate in OR
• Anticipate post-op need for pain control (epidural, PCA)

Question 17

Left vs right liver living donor considerations?

Answer 17

• Healthy donor, no risk for thromboembolic disease, no liver disease
• Left lobe liver donation (segments II and III) is usually done in the context of parent-to-child donation with recipients smaller than 15 kg
  
  • Major procedure but much lower risk vs. right , doesn’t have high comp rate
  • Laparoscopic vs. open
• Right hepatectomy needed for adult-to-adult liver transplantation
  
  • major procedure with significant risk!
  • residual liver volume of the donor must be greater than 35% of original volume
  • Early death among live liver donors in the United States is estimated to be 1.7 per 1,000 donors
  • Complication rates: up to 1/3 of donors:
    
    • air embolism, atelectasis, pneumonia, respiratory depression, and biliary tract damage (then jaundice, ERCP, symptomatic, pain)
  • Reserved for healthier recipients
• When lift/twist liver have no BP. When start bleeding usually parenchymal tissue of liver not big vessels, so very difficult to control bc a mill little bleeders not just 1 vessel to clamp & intrinsic/extrinsic clotting that’s impacted w/ coag status and functional ability of liver & vol status w/ hemodilution if do mass resus

Question 18

Anesthesia consideratiosn with right liver living donor?

Answer 18

• Significant hypotension with cross-clamping hepatic pedicle
  
  • Debate over volume loading (prevent renal compromise; decrease air embolism risk) vs. volume restriction (decreased blood loss) if hemodilute what you lose has less blood content in it vs hemoconc easier for surgical control. Surgeon pref
  • Vasopressin and norepi will augment physiologic levels to compensate – talk to surgeon. If acute compromised HD tell them can manip liver and improve situation
• Right hepatectomy usually done open vs L can be lap
• CVL +/- (need for CVP monitoring is often surgeon preference).
  
  • If no CVP, need ability for mass resuscitation, large bore IV; track CVP if trying to keep dry ~6
• EBL <1 Liter; good cell-saver case bc no malignancy, healthy pt. could be mass BL, just depends
• Avoid hypothermia
• Plan for OR extubation
• Pain control (epidural, TAP catheters, PCA) v painful bc big open abd procedure
• Postop:
  
  • Hypophosphatemia is common
  • Liver function tests including INR are abnormal
    
    • usually return to baseline levels within 3 months; may persist up to 1 year
    • some donors have chronic low platelet counts after hepatectomy

Question 19

What is involved in the workup for the kidney recipient?

Answer 19

• Screened for tumors (mammography, Papanicolaou test, colonoscopy, prostate specific antigen) –all organ recipients go to r/o active malignancy- often CI d/t increased r/f further malignancy secondary to high dose anti-rejection medications)
• Screened for infection (dental evaluation, viral serologies) look at valves or bad dentition at r/f infection, do full mouth extraction ie bad AR, very sick, go to sleep for dental extraction before valve lot of local and only little anesth
• Optimize co-morbidities
  
  • CV risk factor modification: control htn & hyperlipidemia
• Good control of diabetes before transplant
• Evaluation for psychiatric stability and social support, transportation, financial support
• Severe heart, lung, or liver disease; most malignancies; and active or untreatable infections such as tuberculosis are exclusion criteria for renal transplantation.
• latent infections (TB) + anti-rejection meds ^immunsupp**à infections will re-colonize and cause probs. i.e.: s/p heart tx 1st 5 yrs= high r/o dying from rejection. At 10 yrs- 27% will have a malignancy d/t high dose rejection meds

Question 20

Preoperative considerations prior to kidney transplant?

Answer 20

NOT AS RUSHED (rushing time is d/t allowable ischemia time) – have time for w/u beforehand, good can get HD

• Commonly have hypertension and/or diabetes mellitus —2 leading causes for needing a transplant
• Increased risk for coronary artery disease and congestive heart failure
  
  • Review CV workup (TEE, EKG, enzymes)
  • Frequently hyperdynamic if they are fluid overloaded
• Evaluate electrolyte and acid-base abnormalities, anemia, and platelet dysfunction (uremic)
• PFTs are particularly important in type 1 diabetics (kidney-pancreas)
  
  • Common issues with reduced lung volumes and diffusing capacity
• Preoperative dialysis is recommended when feasible – see how graft working, how much fluid off, any problems
  
  • If HD pre-op: may be dry- if a lot of fluid off give ~250mL fluid in pre-op = smoother induction bc already contracted intravascular space bc of chronic HTN, don’t tolerate induction well but if also dry, tank @ induction

Question 21

Preop/induction considerations for kidney transplant?

Answer 21

• Usually GETA
  
  • Epidural/ spinal concerns: uremic plt dysfunction and residual heparin after pre-op dialysis
• Case time 3 hours or less; supine; kidney will be placed in right iliac fossa (most common) or retroperitoneal space
• Pre-meds (Tylenol, H2 blocker to combat anaphylactoid rxn w/ 1st dose of immunosupp) especially if you will be starting the first immunosuppressant (ATG); Midazolam is commonly given
• RSI (diabetes, gastroparesis, uremia)—may or may not have met NPO criteria (uremia huge risk factor for inc resid vol and asp)
• Expect difficult IV & CVL access- CVP will likely be needed; have usg available
  
  • bc had multiple access sites/rep vasc cath & vasculopathic bc DM & HTN. Look @ RIJ w/ US & clotted off or look ok but move US down and see cant thread. When thread wire, if meet resistance, take it out don’t try to pass it thru. If L bad too, can do fem or surgeon can help.
• Foley, NGT
• Give pre-incision antibiotic
• Give Benadryl 50 mg & Solumedrol 500 mg after induction if you will be starting ATG (immunosuppression)

Question 22

Maintenance considerations for kidney transplant?

Answer 22

GOAL: PRESERVE RENAL BLOOD FLOW

• Volume loading and general avoidance of pressors: usually get ~3 liters in volume load before new kidney is in (crystalloid vs. albumin)- monitor CVP as guide (often give 1 L crystalloid and then switch to albumin)
• General goals: systolic pressure > 90 mmHg, mean systemic pressure > 60 mmHg, and CVP > 10 mmHg
• Blood products not usually needed; available- not just T&S, have T&C.
• Choice of inhalational agent does not impact outcome (Sevo, Des, Iso all fine), bal anesth
• Avoid Morphine and Demerol; Fentanyl is usually used (don’t want active metabolites)
• May want to use a NDNMB w/ Hoffman elimination (Atracurium/ Cisatracurium)- cis better bc no histamine release (already have antirejection drugs that cause histamine release). Int w/ sux for RSI, K prob ok if HD. Then switch to nimbex (cis)
  
  • Transplant surgeons tend to REALLY like NMB’s; keep relaxed until fascia closed at least
  • Use TOF monitor to guide & don’t try to get back breathing til very end of case
• Good glucose management; monitor electrolytes throughout
• Anticipate administration of furosemide (40 or 80mg) and mannitol (0.5gram/kg)
  
  • Timed around first anastomosis (per Barash); usually give few mins b4 unclamp. When ask for tiny suture = anastomosis & pay attn to sx
• Monitor UOP after unclamping – make sure foley bag totally drained & start looking for urine
  
  • Unclamp: organ has hyperkalemic, acidotic, preservative in it–may see lactic acidosis and K go to systemic circ– may need Ca (helps w/ hypotension and transient hyperk to dec effects of K on heart membrane)

Question 23

Emergence considerations in kidney transplant?

Answer 23

• Expect to extubate: evaluate closely for fluid overload before making this decision bc of comorbs
  
  • Tachypnea, diaphoresis, rales, hyperdynamic: caution; may have to stay on vent until fluid off. Don’t assume pain, ausc.
  • Ensure NMB adequately reversed
  • Increased risk for post-op respiratory depression with narcotics
• Pain control: consider TAP blocks or combo blocks ilioinguinal-iliohypogastric and intercostal nerve blocks; PCA
  
  • NSAIDs & COX-2 contraindicated!
  • Post-op pain is expected to be severe
• Post-op complications:
  
  • ureteral obstruction and fistulae, vascular thromboses, lymphoceles, wound complications, and bleeding

Question 24

Anesthesia considerations for pancreas transplant?

Answer 24

same stuff from kidney but + a line

• Pre-op: Evaluate Type I diabetes complications
• The main thing that is different on a Pancreatic TP (75% are getting a kidney too) is that they all get arterial lines because a kidney/pancreas TP is very long and we check blood sugars every 15- 30 minutes after the pancreas is in
• Anticipate ICU admission: need to be monitored for complications more closely
• Blood sugar control: do NOT be overly aggressive; can plummet after the pancreas is in- Want 120-180
• Insulin gtt needs concurrent D5 infusion and frequent blood sugar checks!!!

Question 25

Liver anatomy review?

Answer 25

• largest internal organ in the body
• 25% to 30% of the cardiac output
• dual blood supply
  
  • hepatic artery provides 25% (50% of O2 delivery)
  • portal vein provides 75% (50% of O2 delivery)

Functions:

• metabolic pathway of carbohydrates, fats, and proteins.
• glucose is stored as glycogen and is converted by the liver to lactate, with the generation of energy.
• Protein is metabolized to ammonia and urea for excretion
• produces nearly all the plasma proteins, except immunoglobulins; produces albumin, the body’s primary transport protein and major determinant of oncotic pressure. ESLD w/ hypoalbuminemia
• drug metabolism, especially via the cytochrome p450 isoenzymes.
• hormone, vitamin, and mineral metabolism
• hepatic synthesis of procoagulant factors such as the vitamin K–dependent coagulation factors; the liver also produces the anticoagulant factors protein C, protein S, and antithrombin III- complex prob w/ liver dx of anticoag abnormals & procoag abnormals. Mass bleeding & issues w/ clotting or maintenance of clots or production of clots w/o suffic clot breakdown because don’t have protein C
• sequesters platelets

Question 26

CNS, Pulmonary and CV S/S seen with ESLD?

Answer 26

• CNS
  
  • encephalopathy- fatigue
    
    • BBB disruption and intracranial HTn (in acute liver failure)
• Pulmonary
  
  • respiratory alkalosis
  • reduced diffusing capacity- hypoixemia/hepatopulmonary syndrome
  • pulm htn- reduced R heart function
• CV
  
  • Reduced Svr- hyperdynamic circulation
  • Diastolic dysfunction
  • prolonged QT
  • Blunted response to inotrop
  • blunted response to vasopressor
  • diabetes
  • caution with TEE with bleeding esophageal varices!!!

Question 27

GI/Renal, hematologic, endocrine, and other s/s with ESLD?

Answer 27

• GI
  
  • gastrointestinal bleeding from varices- caution TEE
  • Ascites
  • delayed gastric emptying
  • nutritional/metabolic- muscle wasting and weakeness
• Hematologic
  
  • decreased synthesis of clotting factors- risk of massive surgical bleeding
  • hypersplenism (pancytopenia)- prone to injury
  • impaired fibrinolytic mechanisms
• Renal
  
  • hepatorenal syndrome- impaired renal excretion drugs
  • hyponatremia
• Endocrine
  
  • glucose intolgerance
  • osteoporosis- fracture susceptibility
• Other
  
  • poor skin integrity; pruritis
  • increased VD of drugs
  • decreased citrate metabolism- calcium requirement with rapid fresh frozen plasma infusion

Question 28

Liver transplant selection

Answer 28

• Patients with Acute Liver Failure are given priority for donor livers, then the patients with the highest MELD/PELD score and compatible blood group are next
• Screened for infectious diseases: HIV, CMV, and Epstein-Barr virus
  
  • major infection and malignancy may exclude patients from consideration for transplantation
• MELD score: determinant of where patient is on “the list”
• MELD variables: creatinine, bilirubin, INR, sodium (added in 2016) memrozie meld score variables
  
  • Hyponatremia associated with increased mortality in ESLD
• ALF: viral, acute hepatitis, Wilson dz, drug induced= will be first on list!
• HIV positive still get livers at some centers

Question 29

Renal and CV preop considerations in ESLD patients?

Answer 29

• Renal dysfunction very common and creatinine not reflective of severity
  
  • Lack of muscle mass makes creatinine a poor marker – small elevation could mean a lot of renal dysfunction
• Hepatorenal syndrome
  
  • Increased renal vasoconstriction, a reduced GFR, subsequent increase in creatinine, and impaired sodium and water excretion
• CV:
  
  • CAD common: needs extensive cardiac workup; 30-day mortality post-op is highest from CV causes
    
    • Stress test, cardiac cath, might need angioplasty pre-op if stenotic, echo
    • Assess functional ability
    • Very low SVR, high cardiac index, and increased mixed venous sat (not using oxygen effectively)
    • Complicated to take care of bc vasodilated & hypderdynamic
    • Cirrhotic cardiomyopathy (will have blunted response to beta agonists and vasopressors)
      
      • Need echo; systolic and diastolic dysfunction
    • HOCM (hypertrophic CM): may require pre-op septal ablation to prevent inc risk post-op

Question 30

What is hepatorenal syndrome patho?

Answer 30

• Hepatorenal syndrome
  
  • Increased renal vasoconstriction, a reduced GFR, subsequent increase in creatinine, and impaired sodium and water excretion
• Patho of hepatorenal syndrome:
  
  • Portal hypertension leads to profound systemic and splanchnic vasodilatation and intravascular volume depletion. This increases renal vasoconstriction via both the renin–angiotensin–aldosterone pathway and sympathetic nervous system activation. Renal vasoconstriction leads to significant hypoperfusion of the kidney =Vol overloaded but intravascularly depleted.
  • Patients usually in renal failure by liver tx

Question 31

Pulmonary considerations for ESLD?

Answer 31

• Evaluate presence of portopulmonary hypertension: PA pressure of _>_25 mmHg, PVR >240 dyne, and PAOP 12 mmHg or lower
  
  • High risk perioperative death
  • mean PA pressure > 50 mmHg is an absolute contraindication to liver transplantation d/t r/f RHF
  • Right heart evaluated before surgery
• Evaluate PFT’s & presence of hepatopulmonary syndrome
  
  • Marked A-a gradient, intrapulmonary shunting with hypoxia
  • Pleural effusions common- due to osmotic gradient issues

Question 32

Considerations with Hep C in ESLD patient?

Coag studies in ESLD?

Benzo use in ESLD?

Answer 32

• Recent treatment for Hep C? Some of the newer agents have interactions with peri-operative meds
  
  • Ex: Telaprevir inhibits CYP3A; protease inhibitors prolong Midazolam effect
• Lab evaluation: coag studies do not accurately predict bleeding in this population – look @ bleeding on the field, use coags as guide
  
  • fragile balance between low levels of both procoagulation and anticoagulation factors
• Must use BZD with caution esp in encephalopathic patients
  
  • Become hypercarbic d/t dec RR—cause PVR inc (PA clamps down) and worsening chronic RHF—superimposed w/ acute RHF and become way worse. Don’t like to give benzos to lungs either.

Question 33

What are changes that impair hemostasis in ESLD?

Answer 33

• Thrombocytopenia
• plt functiond effects decreased
• low levels of alpha2-antiplasmin, factor XIII and thrombin-activatable fibrinolysis inhibitor
• low levels factors II, V, VII, IX, X, and XI
• Vit K deficiency
• dysfibrinogenemia
• elevated Tissue plasminogen activator levels
• enhanced production of Nitric oxide and psostacyclin

Question 34

What are changes htat promote hemostasis in ESLD?

Answer 34

• Elevated levels of VWF
• Decreased levels of ADAMTS-13
• Elevated levels of factor VIII
• Decreased levels of protein C, protein S, antithrombin, alpha2-macroglobulin and heparin cofactor II
• Low levels plasminogen

Question 35

Anesthesia setup for liver transplant?

Answer 35

• RSI: secondary to gastroparesis & ascites; usually done as an emergency case (not often NPO)
• Art line (1 or 2) Radial and +/- Femoral – central prs much higher vs periph, decisions done w/ central prs
  
  • ​difference in pressures most pronounced right after reperfusion of liver
• PA catheter to follow PVR (some centers; based on patient)
  
  • monitors R heart function
• TEE (caution with bleeding- varices); TEG to evaluate coagulation
  
  • TEE limitations: expertise required, limited transgastric views during key portions of the operation, the potential for esophageal varix rupture and difficulty in obtaining quantitative measures of CO in the absence of tricuspid regurgitation.
• Ability to monitor labs frequently (I-stat, lab support)
• Rapid infusion catheters (RIC)- 14 gauge peripherally; CVL- have usg available. Not hard to get IV on
• Belmont or another rapid infusion system primed and ready
• Colloids; Blood & products in the room (10 PRBCs, 8 FFP , 4 platelets)
• Active warming mechanisms bc hypothermia affects coag
• Foley/ NGT
• Maintenance: Balanced technique: Narcotic, Inh agent (No N20), NMB
• Case will progress in 3 phases: dissection, anhepatic phase, neohepatic phase

Question 36

What are the 3 phases of liver transplant

Answer 36

1. dissection
2. anhepatic phase
3. neohepatic phase

Question 37

Anesthesia considerations during dissection phase of liver transplant?

Answer 37

aka pre-anhepatic phase

• Native liver is dissected and removed
• Major anesthetic goals of this phase are correction of coagulopathies and maintenance of intravascular volume for renal protection
• Compression or occlusion of major blood vessels—25-30% blood to liver, will see hypotension (major swings in BP)
• Large-volume (>5 L) drainage of ascites at incision requires albumin to prevent renal decompensation (give 6 to 8 g/L of ascites drained)
• Ends in the clamping of the inferior vena cava, portal vein and hepatic artery, and removal of the liver
• Some centers use veno-venous bypass- not common to use perfusionist- just have them on standby
  
  • Venous blood from the inferior vena cava and femoral vein is returned into the internal jugular vein using extracorporeal venovenous cannulas and a centrifugal pump
  • No strong advantage and risk of VAE, thromboembolism, hypothermia

Question 38

What are som considerations with replacement of intravascular volume and correction of coagulopathies during pre-anhepatic phase of liver transplant?

Answer 38

• Significant blood loss during this phase- follow TEG (complex interaction of pro and anti-coagulant factors)
• Giving balance of PRBCs, FFP, cryo, and plts. Prefer not to give plts
  
  • FFP is used to maintain an INR of 1.5 or less in patients with anticipated or ongoing bleeding
    
    • May need Ca++ due to inability to metabolize citrate - FFP highest citrate
  • Keep Fibrinogen above 150 mg/dL with cryoprecipitate: critical for hemostasis
  • Plt >50k but plt transfusions lead to poorer outcomes/ may not need w/ cryo/ FFP
  • Cell-saver if not a tx for cancer (hepatocellular carcinoma)
  • Activated factor VII: rescue of refractory critical bleeding unresponsive to more standard management
  • Tranexamic acid or ε-aminocaproic acid (EACA; 5-g load and 1 g/hr infusion) may be needed
• Ensure adequate volume replacement- colloids preferred
• Pulmonary embolization risk during LT
  
  • patent foramen ovale— (need ECHO with bubble test to see if pro-patent PFO present).
• Advantage of TEE: detect pro-patent PFO & Real time volume status. If R heart acutely enlarges PFO flaps open, emboli can cause mass CVA. Pro-patent PFO means not open all the time just open w/ stimulation*
• coagulopathy and hypercoagulability can cause simultaneous and serious problems—two distinct diseases rather than a balanced system. In general, prohemostatic factors are also elevated in patients with liver disease, including von Willebrand factor and factor VIII, and low values of ADAMTS-13, antithrombin, protein C, and plasminogen disrupt the normal balance of hemostatic factors

Question 39

What happens during the anhpeatic phase of liver transplant?

Answer 39

• With cross clamping of the portal vein and IVC, cardiac output (CO) may decrease by up to 50%
  
  • To avoid this sudden loss of preload, volume loading should occur prior to crossclamping
• Some surgeons use a “piggyback” technique where the inferior vena cava is only partially occluded
  
  • Less derangement in hemodynamics
• Alternatives include the use of a temporary portocaval shunt or venovenous bypass.
  
  • V-V bypass has fallen out of favor

Question 40

What occurs during the anhepatic phase during the transition to neohepatic phase?

Answer 40

• New liver is anastomosed into place and re-perfused
  
  • Vena cava unclamped, adequate return of venous return to the heart is restored
    
    • Blood pressure and cardiac output improve transiently- all BF restored to heart BUT when portal vein is open….
  • Portal vein is then opened: cold, acidotic, hyperkalemic blood from below the clamp and from the liver graft circulates directly into the right heart/central circulation
    
    • Significant drop in blood pressure, bradycardia, other arrhythmias, and occasionally cardiac arrest: reperfusion syndrome- massive drop in BP, etc.
      
      • Surgeon must communicate when they intend to unclamp portal vein
      • Reduce effects with perfect timing of calcium chloride & bicarbonate
      • Have available for immediate use: +/-epinephrine, and +/- vasopressin, +/- lidocaine, +/- atropine, +/- methylene blue (vasoplegia of reperfusion; methylene blue for refractory to all pressors)
  • The time taken to sew the new graft in place is the warm ischemia time
    
    • Warm ischemia is very damaging to the graft, limiting warm ischemia time is critical to graft success
    • any emergency at this time that slows down anastomosis can affect the graft long-temr
• Postreperfusion syndrome: decrease in MAP by 30% for at least 1 min within 5 min of reperfusion reported in 12.1%-42% of patients

Question 41

What occurs during neohepatic phase of liver transplant?

Answer 41

• Hepatic artery and bile duct anastomoses; usually with a cholecystectomy
• Looking for signs that the new liver is beginning to function:
  
  • improvement in acidosis
  • clearing of lactic acid
  • improved hemostasis
  • production of bile
• Renal function hopefully improves after reperfusion
• Assess bleeding on field and need to use antifibrinolytics (should be improving as coag factors are being produced)
• Sources of surgical bleeding are corrected
• Drains are placed and the abdomen is closed
• Consider extubation based on surgical course and fluid status
  
  • Check TOF & reverse; assess cardiopulmonary and ventilatory status
• First 30 minutes: base deficit improves with graft metabolism of citrate and lactate
• 1^st hour: CO decreases as SVR increases with graft metabolism of vasoactive substances unleashed at reperfusion
• Graft should appear smooth edged with no evidence of engorgement - want to optimize perfusion, acid-base, fluid status during this time of tension

Question 42

Types of lung transplants?

Answer 42

• Low availability; lengthy waiting list time (500-1000 days)
• Options:
  
  • single lung transplant,
  • en bloc double (cut bronchial tree & put both lungs in at same time),
  • sequential double (take out worse lung, put in new lung, & then take out other lung & put new lung in, same case), and
  • heart- lung transplantation
• Long-term survival after bilateral lung transplantation is better than after single-lung transplantation
• Double lung is required if pathological process in remaining lung would jeopardize new lung (ex. CF; severe emphysema- hyperinflated other lung bc the dynamics to ventilate old lung will ruin new lung; severe pulmonary htn), pulm fibrosis restrictive lung dx often only need single
• Trend is moving away from using CPB – after induction do TEE & then decide if need bypass dep on how bad RHF is

Question 43

Indications for lung trasnplant?

Answer 43

• Indication: poor pulmonary function despite maximal medical therapy
• COPD:
  
  • O2 requirement
  • FEV1 <25% of predicted value after bronchodilators and/or PaCO2 = 55 mmHg and/or pulmonary hypertension (especially with cor pulmonale) know specific physiologic differences of pt that affect anesthetic mgmt. vs the criteria for tx
• Idiopathic Pulmonary Fibrosis
  
  • Vital capacity <60%-65% of predicted
  • Resting hypoxemia
  • Progression of disease despite therapy (steroids)

DON’T NEED TO MEMORIZE SPECIFIC INDICATIONS FOR TRANSPLANT, FOCUS ON ANESTHETIC MGMT

Question 44

Lung transplant screening?

Answer 44

• Rule out malignancy (mammography, Papanicolaou test, and colonoscopy)
• PFT, left and right heart catheterization, and TTE
• CF patients can be successfully transplanted despite chronic bacterial infections (if waited not to have infection, would never get tx)
• Continue bronchodilators, steroids, and pulmonary vasodilators perioperatively – continue all long-term therapies

Question 45

Considerations for lung transplant patient?

Answer 45

very little amount of cold ischemia time!

• Emergency case so may be a full stomach; RSI
  
  • metoclopramide, histamine-2 antagonists, nonparticulate antacid
• Minimal reserve: caution with pre-op sedation; small doses Versed (use benzos w/ great caution d/t RHF)
• Chronically intravascularly volume depleted
• Pulmonary hypertension is common impacts induction
• GETA w/ +/- thoracic epidural
• CVL, PAC, A-line (have ultrasound on board)
• FOB (fiberoptic bronch), Double lumen tube- multiple sizes
• Post-op pain control plan: thoracic epidural, paravertebral blocks, intercostal nerve blocks; multi-modal analgesia
  
  • want to minimize opioids if poss to allow for maximal lung expansion post-op. LOTS OF PAIN!
• DON’T EXTUBATE!- stay intubated. Kidney prob ext, liver might ext, lung & heart stay int

Question 46

Positioning, induction and maintenance concerns in lung transplant?

Answer 46

• Lateral thoracotomy; usually lung with poorer function is replaced if single
  
  • Bronchial anastomosis more common than tracheal anastomosis for technique – intact cough
• Prone to hypotension with induction (intravascular volume depletion)
  
  • Reduce doses
• Maintenance: balanced anesthetic (volatile agent plus narcotic w/ NMB) fluid mgmt. & surgical course whats diff vs anesth
  
  • Avoid N2O: may exacerbate bullous emphysematous disease, pulmonary hypertension, or intraoperative hypoxemia
• Fluid restriction is optimal; use small volume colloids (CVP<7) ideal: 6
  
  • Use pressors to support!- usually have a neosynephrine gtt running
• Use lung protective ventilation
  
  • tidal volumes (6 mL/kg), PEEP, lowest acceptable Fio2 settings
  • Use PCV
• Hypoxemia during single lung ventilation:
  
  • PEEP to the dependent lung
  • CPAP to the nondependent lung
  • PA clamping of the nonventilated lung by the surgeon

Question 47

When might CPB be used during lung transplant?

Answer 47

Indications for CPB:

• Inability to oxygenate despite above efforts
• inability to provide adequate ventilation
• RV failure: TEE is very helpful to evaluate RV and need for CPB.
  
  • After induct & DLT placement, TEE à DLT regular induction, place SLT, adeq anesth depth, set up FOB, place DLT, confirm placement of DLT, do optimal ventilation, they do TEE and look at RH and based on pts abil to oxygenate & how RH looks, decide about CPB

Question 48

Considerations after reanastomosis of lung?

Answer 48

• Following re-anastomosis of atrial/pulmonary vein patch, bronchus, and PA, lung is unclamped and perfused
  
  • Hypotension can be seen but not usually as severe as liver
• Hemostasis is checked; may use FOB to remove secretions & blood from freshly anastomosed lung
• Ventilation is attempted with new lung
• After closing, attempt to exchange DLT for single lumen ETT over a catheter
  
  • Indications to wait on exchange: Significant oropharyngeal edema, high PEEP requirement, or need for differential lung ventilation

Question 49

Use of DLT versus bronchial blockade technique?

Answer 49

• Double-lumen tube vs bronchial blockade techniques:
  
  • DLT: allows better suctioning of secretions, improved deflation of the operative lung during dissection, and application of continuous positive airway pressure to the operative lung if indicated.
  • BB: more easily dislodged with surgical manipulation, may not provide isolation of the right upper lobe, and requires repositioning midsurgery in the case of a bilateral sequential procedure.

Left-sided endobronchial tube is preferred, because Right-sided tube may be difficult to position relative to the right upper lobe bronchus.

Question 50

Considerations in double lung transplant?

Answer 50

• Supine position, using a “clamshell” incision vs. midline sternotomy (need to drop lungs b4 the sternotomy so don’t inj ury to lungs w/ saw)
• En bloc double-lung transplantation requires CPB, can use standard ETT
• Bilateral sequential transplantation requires lung isolation (DLT)
• Expect severe pain post-op
  
  • Thoracic epidural advisable

Question 51

What are some potential lung transplant complications?

Answer 51

• Acute transplanted lung failure: acute graft rejection, inadequate pulmonary venous drainage- fluid overload, primary graft dysfunction
• Primary graft dysfunction: allograft dysfunction within 72 hours of transplantation
  
  • Factors: prolonged organ ischemia time with ischemia/reperfusion injury, advanced donor age, recipient pulmonary hypertension, and the use of CPB (poor donor and recipient criteria)
  • ECMO has been used
• iNO therapy (nitric oxide) may be used to decrease PVR and improve oxygenation perioperatively
  
  • Methemoglobinemia risk
• Sx acute rejection:
  
  • peri-hilar infiltration on x-ray;
  • significant decreases in forced expiratory volume in 1 second, vital capacity, and total lung capacity
  • obstructive pattern; blood gas with significant A-a gradient
• Lung Protective Strategies: Obstructive pattern: inc I:E ratio to 1:2.5- 1:3*
• Restrictive pattern: normal I:E or drop to 1:1 and improve their ventilation

Question 52

Selection criteria for heart transplant?

Answer 52

• Class III or IV heart failure despite optimal medical therapy.
  
  • Most common: severe LV systolic dysfunction (LVEF less than 20% usually), PVO2 <12mL/kg/min
  • Occasional: refractory angina, unmanageable dysrhythmias, diastolic heart failure
  • Irreversible pulmonary hypertension is a contraindication. New heart cant handle high PVR
  • Other potential contraindications: other systemic co-morbidities that would impact survival (renal or hepatic failure could impact ability to tolerate immunosuppresive agents)
  • severe atherosclerosis is a contraindication
  • (FEV1) less than 50% predicted despite optimal management of CHF will have increase in post-op respiratory failure

Question 53

Preop heart transplant considerations?

Answer 53

• Cold ischemia time is about 6 hours or less optimally
  
  • Ischemic time for the donor heart starts with aortic cross-clamping during the harvest and ends with removal of the cross-clamp from the recipient aorta
• Emergent case with fast, efficient evaluation
• Review recent CXR and labs
  
  • Evaluate pulmonary, hepatic, and renal compromise associated with CHF
• Mobilize blood products (FFP, cryo, plt, PRBC’s) & in room
• Evaluate and setup much like any other open heart
• Determine of any prior aprotinin exposure (anaphylaxis with re-exposure- esp within 6 mos; will use something else like amacar) – if prev sternotomy

Question 54

Preinductions considerations for heart transplant?

Answer 54

• Evaluate current inotropic infusions, chronic medications for heart failure, presence of LVAD; pacemaker or defibrillator- repeat sternotomy= more bleeding
  
  • Antiarrhythmic devices need to be interrogated and reprogrammed to a mode that will not be affected by electrocautery interference
  • ACEI (consider vasopressin infusion); anticoagulated? (have FFP)
• A-line before induction; large bore IV for resuscitation prior to induction for resuscitation
• Inotropes and Pressors ready and on-hand (dobutamine or milrinone, epinephrine, norepinephrine, dopamine, vasopressin, and phenylephrine) – some start inotropes on induction, some already on inotrope from ICU (leave running)
• RSI
• Strict infection prevention
• Immunosuppressants may be given prior to incision
• Evaluate patency for CVL/ PAC placement and have usg present

Question 55

Induction/maintenance considerations for heart transplant?

Answer 55

• Median sternotomy; CPB; recipient heart is excised
  
  • Variety of techniques; residual P-wave with bi-atrial technique (still have residual non-functioning SA node- no impact on HR or CO but will have another p wave)
• High-dose narcotic techniques for induction and management varies ie 20 cc fent, 10 versed, .4 iso
  
  • Alternative is balanced technique with lower doses of narcotics, and inhalation anesthetics
• Neuromuscular blockade needed
• Hypotension may not respond to ephedrine or phenylephrine (catecholamine refractory-may need epi and inotropes)
• TEE examination should be performed after induction of anesthesia and after weaning from CPB- (required before take out native heart and after put in recipient heart) –preferred for livers, done most places for lungs and required for hearts
  
  • risk of intracardiac thrombus is increased in the recipient heart
• Heparin dosing is similar to that for other CPB procedures (big dose before going on bypass)
• Cannulation is done so that the surgical field is bloodless (cannulate SVC, IVC and aorta)
• Prior to resection of the native heart, the PAC should be withdrawn from the surgical field
  
  • can be readvanced after removal of the superior cava cannula
• Maintenance of CPB and weaning from CPB are associated with the same issues as for other cardiac surgical procedures
  
  • Temp- rewarming, acid/base, electrolytes

Question 56

Considerations when weaning from CPB during heart transplant?

Answer 56

• Weaning from CPB done in similar fashion to other open heart surgery
• Air should be evacuated prior to weaning from CPB
• Prior to weaning from CPB, the heart is reevaluated with TEE to look for air
• Donor heart is denervated: feedback for inotropy and chronotropy are lost
  
  • Isoproterenol is used frequently for its direct effects on cardiac β- receptors to increase graft heart rate
  • Temporary pacing may be needed
  • Atropine will not work for them
• Acute right heart failure is a complication b/c donor right heart not used to high PVR

Question 57

Post heart transplant considerations in regards to autonomic influence?

Answer 57

• severed from autonomic influence
  
  • HR determined by intrinsic rate of SA node
  • patients have resting tachycardia (HR 100-120 BPM)
• If CO is product of HR x SV, then CO becomes dependent on preload
  
  • heart transplant patients very sensitive to hypovolemia
• Drugs that cane be used to increase HR
  
  • Since no autnomic input from cardiac accelerator fibers or vagus nerve
    
    • drugs that directly stimulate SA node can be used to increase HR (epi, isopril, glucagon)
    • drugs that indirectly stimulate SA node canNOT be used (atropine, glyco, ephedrine)
      
      • peripheral attempts to induce hemodynamic changes (carotid massage, valsalva maneuver, or DL) will have no affects
  • B receptor effects of Epi/NE are exaggerated in transplanted heart (versus alpha effects which are not exaggerated)
• Other considerations:
  
  • although cholinesterase inhibitors won’t cause bradycardia, they can cause other s/s of PSNS activation elsewhere in body, so still pretreat
  • may see 2 p waves on EKG
    
    • one corresponds to recipient intrinsic SA ndoe and one from donor herat
      
      • native heart may react to fluctuation in autonomic input, but will not affect cardiac funtion
  • any reflex that requires ANS innervation will be disrupted in denervated heart
    
    • exception to this is bainbridge– SA node stretch will directly increase SA node’s firing rate

Question 58

Denneravation heart transplant pharamacology?

med, effect on recipient, mechanism?

Digitalis

Atropine

adrenaline

noradrenaline

isopril

quinidine

verapamil

nifedipine

hydralazine

b-blcoker

Answer 58

• Digitalis
  
  • effect-normal increase of contractiliy,
    
    • mech- direct myocardial effect
  • effect- minimal effect on AV node
    
    • mechnism- denervation for av node
• Atropine
  
  • no effect on recipient
  • mech- dendervation
• Adrenaline
  
  • effect- increased contractility,
    
    • denervation, hypersensitivity
  • increased chronotropy
• Noradrenaline
  
  • effect- increased contractility,
    
    • mech- denervation
  • effect increased chronotopry
    
    • mech- no neuronal uptake
• Isopril
  
  • effect- normal increase in contractility, normal increase in chronotropy
• Quinidine
  
  • effect- no vagolytic effect
  • mech- denervation
• verapamil
  
  • effect- av block
  • mech- direct effect
• nifedipine
  
  • effect- no reflex tachycardia
  • mech0- denervation
• Hydralazing
  
  • effect- no reflex tachycardia
  • mech- denervation
• Bblocker
  
  • effect- increased antagonistic effect
  • mech- denervation

Question 59

Anesthesia pearls for patient s/p transplant?

Answer 59

• Pre-op: focus on determining the degree of immunosuppression and transplanted organ function, evaluating for any co-existing infection, reviewing co-morbidities
• Minimum: CBC, CMP, LFT’s, viral panels/ viral loads PRN, chest x-ray, ECG
• Strict aseptic technique with all invasive procedures
• Active rejection requiring explantation: emergent case right to OR if can take organ out ie kidney vs heart
  
  • Elective or non-urgent cases should be postponed in active rejection or in patients with evidence of active infection
• Regional anesthesia is controversial post-transplant d/t immunosuppression
• Avoid nasal intubation due to immunocompromised state (infection risk)

Question 60

Non-transplant anesthesia considerations?

Answer 60

• Signs of infection are masked in post-transplant patients (may not have fever or inc in WBC), sm inc WBC or change xray w/o fever = stop & get eval
• Evaluate function of grafted organ
• Evaluate liver/ kidney function for necessary pharmacological adjustments
• Significant effects of immunosuppression on renal elimination
• Post renal tx: renal perfusion with adequate volume replacement
• Maintain administration schedule: antibiotic, antiviral, antifungal, and immune suppression regimens
• Avoid NSAID’s in general

Question 61

General guidelines for lung transplant in non-transplant anesthesia?

Answer 61

• Lung tx with tracheal anastomosis: absent cough reflex below suture line due to denervation
  
  • increased risk of retained secretions and pneumonia and have an increased airway hyperreactivity and bronchospasm (below still have innervation and can be hyper-responsive (at bronchial level)
• General guidelines post lung tx
  
  • Evaluate: PFT, arterial blood gas, and chest x-ray results
  • Prefer regional anesthesia when feasible

Question 62

Post-heart transplant considerations with non-transplant anestheisa?

Answer 62

• Post heart tx: denervation
  
  • Rejection presents like CHF
  • ECG and TEE before surgery
  • cannot respond to indirect acting agents, such as ephedrine and even dopamine
  • cannot respond to peripheral attempts to induce hemodynamic changes, such as carotid massage, Valsalva maneuver, or laryngoscopy
  • β-Receptor effects of epinephrine and norepinephrine are exaggerated in heart transplant recipients (versus α effects)
  • Isoproterenol is the mainstay of chronotropic therapy & should be present in the OR
  • General preferred over regional: denervated heart cannot compensate for hemodynamic changes with regional (neuraxial- spinal/epidural)

Primary graft failure can = death. Leading cause of death (5-10years)= malignancy secondary to immunosuppressant therapy

Question 63

Consideraiton with traco level with intraop fluid administration?

Answer 63

• May need to monitor tacro or sirolimus levels intraop and may need add’l dosing if large fluid shifts drop levels- bone marrow tx check trough intraop

Question 64

Infection s/p transpalnt?

Answer 64

• Immunosuppressive therapy
  
  • Infections within 1 month- likely source is allograft (organ has residual infection)
  • 2nd to 6 months: Opportunistic infections; reactivation disease syndromes (TB)
    
    • Trimethoprim-sulfamethoxazole (Septra) prophylaxis for Pneumocystis pneumonia for at least 6 mo’s
    • Inflammatory response blunted; sometimes difficult to identify source of infection
  • >6 months: Many do well & infection risk decreases; some deal with chronic or progressive viral infections (hepatitis B virus, hepatitis C virus, CMV, EBV, herpes zoster)
  • Donor w/ CMV –CMV reinfection intractable seizures

Question 65

Consideratiosn for chronic immuosuppression?

Answer 65

• General side effects:
  
  • Lower seizure threshold, diabetes,
  • CV disease, Diabetes,
  • Increased infection risk,
  • Increased malignancy risk,
  • Pancytopenia,
  • Decreased GFR,
  • Hyperkalemia, Hypomagnesemia
• Immunosuppressed patients who are undertreated risk rejection
• Overimmunosuppression: renal toxicity
• Protocols vary; communicate with transplant team ie lymphatic drainage issues & fresh liver or infection & on acute new immunosupp, talk to team for intraop
• Special attention re: sterile technique
• Maintain antibiotic, antifungal, and antiviral regimens- don’t skip any dosing!

Question 66

Calcinuerin inhibitors MOA, side effects?

Answer 66

• Example- cyclosporine
• inhibits T-lymphocyte activation, differentiation, and cytokine production
• SE: hypertension, hyperlipidemia, ischemic vascular disease, diabetes, and nephrotoxicity
  
  • Cyclosporine
  • Tacrolimus: metabolized by cytochrome P450 3A4 ->upregulation

FOCUS ON S/E of drugs!!!

Question 67

Purine anatagonist MOA, S/E

Answer 67

• Mycophenolic Acids, Azathioprine
  
  • Antiproliferative drugs
  • bone marrow suppression can cause pancytopenia; cardiac arrest and severe upper airway edema occur rarely

Question 68

Corticosteroids MOA/SE

Answer 68

• disrupt expression of many cytokines in T cells, antigen-presenting cells, and macrophages
• SE: hypertension, diabetes, hyperlipidemia, weight gain, GI ulceration

Question 69

Monoclonal MOA/SE

Answer 69

• (ATG, OKT3, IL-2 receptor antagonists)
  
  • Antithymoglobulin (ATG): purified rabbit immunoglobulin G taken from animals immunized with human thymocytes; MOA is depletion of T cells
    
    • Rare: Acute serum sickness:
      
      • sx: jaw pain
      • tx: stop the drug, bridge w/ another drug, plasmapheresis, and corticosteroids