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Thoracic organ transplantation: an overview for perfusionists

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Title: Thoracic organ transplantation: an overview for perfusionists


1
Thoracic organ transplantation an overview for
perfusionists
  • Andreas Hoschtitzky

2
Overview
  • OCTx
  • HCTx
  • HLTx
  • DLTx
  • SLTx

3
History OCTx
  • 1905 Alexis Carrel transplanted a puppy's heart
    into the neck of a dog because of the lack of
    immunosuppression, the experiment was
    unsuccessful.
  • Early investigators included Frank C. Mann of the
    Mayo Clinic, V.P. Demikov of the Soviet Union,
    and Marcus Wong. These early efforts in
    transplantation were thwarted by the infancy of
    cardiopulmonary bypass and a lack of
    understanding of the immune system. As knowledge
    in these areas advanced, so did the field of
    cardiac transplantation.
  • Shumway developed modern day transplantation
    protocols.
  • 1967 Christian Barnard first successful heart
    transplant in a human.
  • 1983 The clinical use of cyclosporine as an
    immunosuppressant revolutionized the field of
    transplantation. Recipient survival rates
    improved, thus producing an explosive increase in
    the number of transplant centers offering cardiac
    transplantation.
  • The remaining limiting factor number of
    available organ donors.

4
OCTx transplantation
  • Indications patients with end-stage congestive
    heart failure with a prognosis of less than a
    year to live without the transplant and who are
    not candidates for conventional medical therapy
    or have not been helped by conventional medical
    therapy.
  • In the US approximately 4000 individuals are
    waiting for hearts. In 1999, about 2000 heart
    transplants were performed in the US. UK around
    300-400 per year.
  • Availability of organs is a major issue.

5
OCTx transplantation
  • Frequency The annual frequency of the procedure
    is about 1 of the general population with heart
    failure
  • Etiology
  • adults
  • Idiopathic cardiomyopathy 54
  • Ischemic cardiomyopathy 45
  • Congenital heart disease
  • and other diseases 1
  • children congenital heart disease and
    cardiomyopathy most common HLHS commonest

6
Pathophysiology OCTx
  • Transplanted heart is unique
  • denervation of the organ makes it dependent on
    its intrinsic rate.
  • as a result of the lack of neuronal input, some
    left ventricular hypertrophy results.
  • right ventricular function is directly dependent
    upon ischaemic time and adequacy of preservation.
  • right ventricle is easily damaged and may
    initially function as a passive conduit until
    recovery occurs.
  • Allograft rejection 2 forms cellular and
    humoral.
  • Cellular rejection is the classic form of
    rejection perivascular infiltration of
    lymphocytes with subsequent myocyte damage and
    necrosis if left untreated.
  • Humoral rejection is much more difficult to
    characterize and diagnose. Generalized antibody
    response initiated by several unknown factors.
    The antibody deposition into the myocardium
    results in global cardiac dysfunction. Diagnosis
    is generally made on the basis of clinical
    suspicion and exclusion because endomyocardial
    biopsy is of little value.
  • Coronary artery disease late process, common to
    all cardiac allografts.
  • Diffuse myointimal hyperplasia of the small- and
    medium-sized vessels, occuring from 3 months to
    several years after implantation.
  • Etiology still unclear, though cytomegalovirus
    (CMV) infection and chronic rejection have been
    implicated. The mechanism of the process is
    thought to be dependent upon growth-factor
    production in the allograft initiated by
    circulating lymphocytes. Treatment
    re-transplantation.

7
Indications OCTx
  • Deteriorating cardiac function and having a
    prognosis of less than 1 year to live NYHA class
    III or IV symptoms
  • EF lt 25
  • Intractable angina or malignant cardiac
    arrhythmias for which conventional therapy has
    been exhausted
  • PVR lt 6-8 Wood units
  • Age lt 65 years
  • Normal renal, hepatic, pulmonary and CNS function
  • Absence of malignancy, infection, recent
    pulmonary infarct, severe peripheral vascular or
    cerebro-vascular disease
  • Ability to comply with medical follow-up care

8
OCTx Donor criteria
  • Brain death
  • Consent next of kin
  • ABO compatible with recipient gt 1year old
  • Within 20 size as recipient
  • No cardiac disease in medical history
  • Normal ventricular wall motion on ECHO
  • Normal heart as assessed by donor team

9
  • 20 recipients die on waiting list though….

10
Management of the Potential Cardiac Recipient
  • TAILORED MEDICAL THERAPY FOR END-STAGE CARDIAC
    FAILURE
  • Conventional outpatient management of congestive
    heart failure includes ACE inhibitors, AR
    blockers, beta blockers, and diuretics
    (especially spironolactone).
  • PHARMACOLOGIC BRIDGE TO TRANSPLANTATION
  • Critically compromised patients require
    admission to the intensive care unit for
    intravenous inotropic therapy. Milrinone,
    dobutamine, and dopamine are the agents of
    choice. Placement of an intra-aortic balloon pump
    (IABP) also may be necessary in heart failure
    refractory to initial pharmacologic measures.
    Patients with continued pulmonary congestion or
    global hypoperfusion despite maximal
    pharmacologic and IABP therapies have been shown
    to improve with placement of mechanical devices
    as bridges to transplantation.
  • MECHANICAL BRIDGE TO TRANSPLANTATION
  • The increased success of cardiac transplantation
    in conjunction with the static number of
    available organs has created a need for
    mechanical assist devices as a bridge to
    transplantation. Ventricular assist devices (VAD)
    or total artificial hearts (TAH) may be indicated
    in potential cardiac recipients who remain
    unstable after 24 to 48 hours of maximal
    pharmacologic support. Since these devices are
    rarely weaned, however, it is imperative that the
    patient's candidacy for transplantation be
    scrutinized prior to placement of a VAD or TAH.
    Patient selection for a mechanical device is a
    complex, evolving field. Recent data shows that
    approximately 70 of patients are successfully
    bridged to transplantation and the actuarial
    survival is 80 at one year. Most large series
    suggest an improvement in survival because the
    devices allow patients to be rehabilitated while
    on the device. Initial results from the
    Randomized Evaluation of Mechanical Assistance
    for the Treatment of Congestive Heart Failure
    (REMATCH) study indicate that patients with
    devices have improved survival and quality of
    life at 1 year compared to medical therapy and
    may prove to be an acceptable long term option in
    those patients who are not candidates for cardiac
    transplantation.
  • LIFE-THREATENING VENTRICULAR ARRHYTHMIAS
  • Symptomatic VT or VF and a history of sudden
    cardiac death (SCD) are indications for placement
    of an automatic implantable cardioverter-defibrill
    ator (AICD), long-term amiodarone therapy, or
    occasionally radiofrequency catheter ablation.
    SCD is the most common cause of death in patients
    awaiting heart transplantation and is most common
    within the first 3 months after referral for
    transplantation. Several studies have shown that
    implantation of a defibrillator improved survival
    in patients with either a history of or inducible
    ventricular tachycardia or fibrillation.

11
Management of the Cardiac Donor
  • Complex physiological phenomenon of brain death
    and the need to coordinate procurement with other
    organ donor teams. Optimal care requires that the
    donor be treated as any other intensive care unit
    patient with invasive hemodynamic monitoring,
    ventilatory support, and meticulous attention to
    intravascular volume status and electrolytes.
  • Continuous monitoring of arterial pressure,
    central venous pressure, and urinary output is
    mandatory. As the number of marginal donors
    increases with the acceptance of more lenient
    eligibility criteria, some transplant centers
    have established mobile intensive care teams that
    are dispatched to ensure appropriate management
    of these highly labile patients.
  • Haemodynamic instability in the donor may result
    from vasomotor dysfunction, hypovolemia,
    hypothermia, and dysrhythmias. Increased
    intracranial pressure may lead to massive
    sympathetic discharge with elevated levels of
    circulating endogenous catecholamines. The
    resultant episodes of systemic hypertension and
    coronary vasospasm place the allograft at
    significant risk of ischemic injury. Rapid
    afterload reduction may be achieved with sodium
    nitroprusside, whereas volatile anesthetics
    assist in reducing the intensity of sympathetic
    bursts. To minimize cerebral edema prior to the
    declaration of brain death, potential donors have
    been intravascularly volume depleted via strict
    fluid restriction and osmotic diuresis.
    Aggressive volume resuscitation is sometimes
    necessary and may require use of a Swan-Ganz
    catheter.
  • Fluid overload, however, should be avoided to
    prevent postoperative allograft dysfunction
    caused by chamber distention and myocardial
    edema. Blood transfusions are indicated to
    optimize oxygen delivery if the hemoglobin falls
    below 10 g/dL. Mean arterial pressure should be
    maintained between 80 and 90 mm Hg. If fluid
    resuscitation is inadequate to restore blood
    pressure in the hypotensive donor, a dopamine
    infusion is initiated for inotropic support.
    Vasopressors are occasionally indicated for
    hypotension caused by loss of systemic vasomotor
    tone. Prolonged administration of high-dose
    catecholamine therapy (dopamine gt1015 µg/
    kg/min) has been associated with poor cardiac
    function in the posttransplant period because of
    depletion of myocardial norepinephrine stores.
    Traditionally, these patients were rejected for
    use as cardiac donors, but high-dose inotropic
    support is no longer an absolute contraindication
    for donation.
  • Maintenance of normal temperatures, electrolyte
    levels, osmolarity, acid-base balance, and
    oxygenation is critical for optimal donor
    management. Common electrolyte disturbances
    include hypernatremia, hypokalemia,
    hypomagnesemia, and hypophosphatemia.97 Central
    diabetes insipidus develops in more than 50 of
    donors because of pituitary dysfunction, and
    massive diuresis complicates fluid and
    electrolyte management.
  • A low-dose aqueous vasopressin (Pitressin)
    infusion is initiated at 0.8 to 1.0 U/h and
    titrated to keep urinary output at approximately
    100 to 200 mL/h. Alternatively, vasopressin may
    be administered periodically subcutaneously or
    intramuscularly (10 U every 4 hours).
  • Standard ventilator management with endotracheal
    suctioning is essential in these vulnerable
    patients.
  • Broad-spectrum antibiotic therapy with a
    cephalosporin is initiated following collection
    of blood, urine, and tracheal aspirate for
    culture.
  • Brain death is associated with the depletion of a
    variety of hormones, including free
    triiodothyronine (T3), cortisol, and insulin.
    Donor pretreatment with hormone replacement
    therapy has proven to be beneficial.

12
Donor Heart Procurement
  • The heart is inspected and palpated for evidence
    of cardiac disease or injury. The SVC, IVC and
    azygous vein are encircled with ties. The aorta
    is dissected from the pulmonary artery and
    isolated with tape.
  • To facilitate access to the epigastrium by the
    liver procurement team, the cardiac team often
    then temporarily retires from the operating room
    table or assists with retraction.
  • Once preparation for liver, pancreas, lung, and
    kidney explantation is completed, the patient is
    administered 30,000 IU of heparin intravenously.

13
OCTx donor operation
The azygous vein and SVC are ligated and divided
distal to the azygous vein leaving a long segment
of superior vena cava. The inferior vena cava
is clamped at the level of the diaphragm (if the
abdominal IVC is vented) and divided proximal to
the clamp to permit efflux of the cardioplegia.
Additional venting is achieved with transection
of the right superior pulmonary vein. The
cross-clamp is applied at the takeoff of the
innominate artery and the heart is arrested with
a single flush (500 mL) of cardioplegic solution
infused through a 14-gauge needle inserted
proximal to the cross-clamp. Rapid cooling of the
heart is achieved with copious amounts of cold
saline and cold saline slush. The apex of the
heart is elevated cephalad and the pulmonary
veins are divided. This maneuver is appropriately
modified to retain adequate left atrial cuffs for
both lungs and the heart if the lungs also are
being procured. While applying caudal traction
to the heart with the non-dominant hand, the
ascending aorta is transected proximal to the
innominate artery and the pulmonary arteries are
divided distal to bifurcation (modification is
necessary if the lungs are being procured).
More generous segments of the great vessels and
superior vena cava may be required for recipients
with congenital heart disease.
14
Donor heart for OCTx
Donor heart is removed from the transport cooler
and placed in a basin of cold saline. Preparation
of the donor heart is accomplished.
Electrocautery and sharp dissection are used to
separate the aorta and pulmonary artery. The
left atrium is incised by connecting the
pulmonary vein orifices and excess atrial tissue
is trimmed forming a circular cuff tailored to
the size of the recipient left atrial remnant.
15
Organ preservation OCTx
  • Safe ischaemic period is around 4 to 6 hours,
    beyond this marginal donors.
  • Postoperative myocardial dysfunction is secondary
    to suboptimal donor management, hypothermia,
    ischemia-reperfusion injury, and depletion of
    energy stores.
  • A single flush of a cardioplegic or preservative
    solution followed by static hypothermic storage.
  • No single preservation regimen has demonstrated
    consistent, clinically significant superior
    myocardial protection when used within the
    current safe limits of ischemia.
  • Controversy surrounds optimal storage
    temperature, composition of cardioplegic and
    storage solutions, techniques of solution
    delivery, additives, and reperfusion
    modification.
  • Hypothermia remains the cornerstone of organ
    preservation. The ideal storage temperature is
    unknown, but most institutions aim for
    temperatures between 4C and 10C.
  • Crystalloid solutions of widely different
    compositions are available and the debate over
    them speaks for the fact that no ideal solution
    currently exists. Depending on their ionic
    composition, solutions are classified as
    intracellular or extracellular.
  • Intracellular solutions, characterized by
    moderate to high concentrations of potassium and
    low concentrations of sodium, purportedly reduce
    hypothermia-induced cellular edema by mimicking
    the intracellular milieu. Commonly used examples
    of these solutions include University of
    Wisconsin, Euro-Collins, and in Europe,
    Bretschneider (HTK) solutions.
  • Extracellular solutions, characterized by low to
    moderate potassium and high sodium
    concentrations, avoid the theoretical potential
    for cellular damage and increased vascular
    resistance associated with hyperkalemic
    solutions. Stanford, Hopkins, and St. Thomas
    Hospital solutions are representative
    extracellular cardioplegic solutions.

16
Organ preservation OCTx
  • Additives for cardioplegic storage solutions
  • The greatest potential for future routine use may
    lie with impermeants, substrates, and
    antioxidants.
  • Impermeants (mannitol, lactobionate, raffinose,
    and histidine) counteract intracellular osmotic
    pressure to reduce hypothermia-induced cellular
    edema in the allograft.
  • The preservation of myocardial high-energy
    phosphates during ischemia (to prevent
    contracture bands) and their rapid regeneration
    at reperfusion (to fuel the newly contracting
    heart) are the primary objectives for the use of
    substrate-enhanced media. Adenosine, L-pyruvate,
    and L-glutamate have been studied most intensely.
  • Recognizing that oxygen-derived free radicals and
    neutrophils likely are critical mediators of
    myocardial reperfusion injury, considerable
    investigative effort has been undertaken to
    modify the untoward effects of ischaemia-reperfusi
    on with antioxidant additives including
    allopurinol, glutathione, superoxide dismutase,
    catalase, mannitol, and histidine.
  • A variety of pharmacologic and mechanical
    strategies for leukocyte inhibition and depletion
    are also being explored.
  • Benefits of continuous perfusion preservation
    techniques are currently overshadowed by
    exacerbation of extracellular cardiac edema and
    logistical problems inherent to a complex
    perfusion apparatus.
  • Experimental low-pressure (microperfusion) and
    intermittent flush techniques theoretically
    provide sufficient oxygen and substrates for
    basal metabolic demands without causing
    significant edema.
  • 20 of peri-operative deaths are still caused by
    cardiac dysfunction….

17
OCTx vs HCTx
  • Orthotopic cardiac transplantation replacement
    of part (or occasionally all) of the recipient's
    heart with a healthy donor allograft.
  • Heterotopic cardiac transplantation, the
    piggy-backing of an allograft onto the patient's
    heart, is rarely performed today. Indicated if
    orthotopic transplantation is not possible
    because of elevated pulmonary vascular resistance
    or when a donor heart is too small to sustain the
    recipient. Results are not equivalent to
    orthotopic transplant.

18
OCTx ANAESTHETIC MANAGEMENT
  • Once donor team has given go-ahead, recipient
    induction commences. High-dose narcotics (e.g.
    fentanyl) usually are employed for induction and
    maintenance anaesthesia.
  • In light of the poor ventricular function of the
    recipient, all anesthetic agents should be
    titrated carefully with inotropic and vasoactive
    agents readily accessible for the rapid
    management of induction-induced hypotension.
    Inhaled agents may be added if necessary, but
    their potential myocardial depressant effects
    limit widespread use in this patient population.
  • Prior to skin incision, some centers initiate
    aprotinin or aminocaproic acid therapy to
    minimize perioperative blood loss.

19
OCTx OPERATIVE RECIPIENT PREPARATION
  • Median sternotomy and vertical pericardiotomy,
    the patient is heparinized and prepared for
    cardiopulmonary bypass. Bicaval venous
    cannulation and distal ascending aortic
    cannulation just proximal to the origin of the
    innominate artery is optimal. Umbilical tape
    snares are passed around the superior and
    inferior vena cava. Bypass is initiated, the
    patient is cooled to 28C, caval snares are
    tightened, and the ascending aorta is
    cross-clamped. The great vessels are transected
    above the semilunar commissures, whereas the
    atria are incised along the atrioventricular
    grooves leaving cuffs for allograft implantation.
    Removal of the atrial appendages reduces the risk
    of postoperative thrombus formation.
  • Following cardiectomy, the proximal 1 to 2 cm of
    aorta and pulmonary artery are separated from one
    another with electrocautery, taking care to avoid
    injuring the right pulmonary artery. Continuous
    aspiration of pulmonary venous return from
    bronchial collaterals is achieved by insertion of
    a vent into the left atrial remnant, either
    directly or via the right superior pulmonary
    vein.
  • Timing of donor and recipient cardiectomies is
    critical to minimize allograft ischaemic time and
    recipient bypass time. Frequent communication
    between the procurement and transplant teams
    permits optimal coordination of the procedures.
    Ideally, the recipient cardiectomy is completed
    just prior to the arrival of the cardiac
    allograft.

20
OCTx implantation
A double-ended 3-0 Prolene is taken through the
recipient left atrial cuff at the level of the
left superior pulmonary vein and then through the
donor left atrial cuff near the base of the
atrial appendage. The allograft is lowered into
the recipient mediastinum atop a cold sponge to
insulate it from direct thermal transfer from
adjacent thoracic structures. The suture is
continued in a running fashion caudally and then
medially to the inferior aspect of the
interatrial septum. Upon completion of the
posterior left atrial suture line, continuous
topical cold saline irrigation of the pericardial
well is initiated, and the patient is oriented in
a left side downhead up position to allow
drainage of the saline away from the operative
field and maximal cold saline exposure of the
left and right ventricles. .
21
OCTx implantation
22
OCTx implantation
  • The second arm of the suture is run along the
    roof of the left atrium and down the interatrial
    septum. It is important to continually assess
    size discrepancy between donor and recipient
    atria so that appropriate plication of excess
    tissue may be performed.
  • The left atrium is filled with saline and the two
    arms of suture are tied together on the outside
    of the heart. Some centers introduce a line into
    the left atrial appendage for continuous
    endocardial cooling of the allograft (5075
    mL/min) and evacuation of intracardiac air Left
    atrial anastomosis is complete, a curvilinear
    incision is made from the IVC toward the RA
    appendage of the allograft. This reduces the risk
    of injury to the sinoatrial node and accounts for
    the preservation of sinus rhythm observed in most
    recipients.
  • The tricuspid apparatus and interatrial septum
    are inspected. Recipients are predisposed to
    increased right-sided heart pressures in the
    early postoperative period owing to preexisting
    pulmonary hypertension and volume overload. Both
    conditions are poorly tolerated by the recovering
    right ventricle.
  • To avoid refractory arterial desaturation
    associated with right-to-left shunting, patent
    foramen ovale is oversewn.

23
OCTx implantation
RA anastomosis is performed in a running fashion
similar to the left with the initial anchor
suture placed either at the most superior or
inferior aspect of the interatrial septum so that
the ends of the suture meet in the middle of the
anterolateral wall. The end-to-end pulmonary
artery anastomosis is next performed using a 4-0
Prolene suture beginning with the posterior wall
from inside of the vessel and then completing the
anterior wall from the outside. It is crucial
that the pulmonary artery ends be trimmed to
eliminate any redundancy in the vessel that might
cause kinking.
24
OCTx implantation
  • Rewarming is initiated at this time. Finally, the
    aortic anastomosis is performed using a technique
    similar to the pulmonary artery except that some
    redundancy is desirable in the aorta as it
    facilitates visualization of the posterior suture
    line.
  • Rewarming is usually begun prior to the aortic
    anastomosis, which is performed in a standard
    end-to-end fashion.
  • Routine de-airing techniques are then employed.
  • Cold saline lavage is discontinued, lidocaine
    (100200 mg IV) is administered, and the aortic
    cross-clamp is removed. Half of patients require
    electrical defibrillation.
  • A needle vent is inserted in the ascending aorta
    for final de-airing with the patient in steep
    Trendelenburg.
  • Inotrope infusion is initiated and titrated to
    achieve a heart rate between 90 and 110 bpm.
    Temporary epicardial pacing wires are placed in
    the donor right atrium and ventricle.
  • The patient is weaned from cardiopulmonary bypass
    and the cannulae are removed.

25
Anatomy
  • Recent trend bicaval anastomoses rather than
    right atrial anastomoses in an attempt to
    decrease the incidence of postoperative tricuspid
    insufficiency.
  • In the transplantation process, the sinoatrial
    nodes of the donor and recipient remain intact,
    and both are present within the recipient. For
    approximately 3 weeks after surgery, the
    electrocardiogram demonstrates 2 P waves
    however, the heart rate and electrical activity
    of the new heart are purely dependent on the
    intrinsic electrical system of the heart and not
    on the neurological input from the recipient.

26
ALTERNATIVE TECHNIQUES FOR ORTHOTOPIC HEART
TRANSPLANTATION
  • Two alternative techniques for orthotopic heart
    transplantation have been gaining popularity over
    the past several years
  • total heart transplantation involves complete
    excision of the recipient heart with bicaval
    end-to-end anastomoses
  • bilateral pulmonary venous anastomoses.
  • The Wythenshawe bicaval technique is performed in
    a similar fashion except that the recipient left
    atrium is prepared as a single cuff with all four
    pulmonary vein orifices. Although these
    procedures are more technically difficult than
    standard orthotopic transplantation, series using
    these techniques have reported shorter hospital
    stays and reduced postoperative dependence on
    diuretics, in addition to lower incidences of
    atrial dysrhythmias, conduction disturbances,
    mitral and tricuspid valve incompetence, and
    right ventricular failure.
  • Furthermore, a recently completed randomized
    study comparing bi-atrial versus bicaval
    transplant showed an improved twelve month
    survival in the bicaval group. Long term outcomes
    and additional randomized studies evaluating
    these alternative techniques are still needed

27
RECIPIENTS WITH CONGENITAL ANOMALIES
  • Unlike children and infants, transplantation in
    adults with previous palliative procedures for
    congenital anomalies is uncommon.
  • Generous donor cardiectomy be performed so that
    sufficient tissue is available for optimal
    reconstruction. There are a variety of
    anomaly-specific implantation techniques.

28
  • Heterotopic Heart Transplantation
  • Pulmonary hypertension and right heart failure
    has remained one of the leading causes of death
    in cardiac transplantation. This has led to an
    interest in heterotopic heart tranplantation.
    Currently, heterotopic heart transplants are
    indicated in patients with irreversible pulmonary
    hypertension or significant donor-recipient size
    mismatch.
  • DONOR ALLOGRAFT PREPARATION
  • Like the cardiectomy for patients with
    congenital disease, the maximal length of aorta,
    superior vena cava, and pulmonary arteries is
    procured. The inferior vena cava and the right
    pulmonary veins are oversewn, and a common left
    pulmonary vein orifice is created. A linear
    incision is made along the long axis of the
    posterior right atrium extending 3 to 4 cm into
    the superior vena cava.
  • Domino Donor Procedure
  • The Domino donor procedure was used to avoid
    wasting relatively healthy hearts from selected
    heart-lung transplant recipients. These organs
    were transplanted into a different recipient
    using standard orthotopic or heterotopic
    techniques.

29
Heterotopic CTx
The sequence of anastomoses is as following
donor left pulmonary vein orifice to recipient
left atrium, donor superior vena cava-right
atrial orifice to recipient right atrium,
end-to-side aortic-aortic anastomosis, and
finally an end-to-side anastomosis joining the
pulmonary arteries of donor and recipient. By
employing this technique, the strengths of both
the native and transplanted heart are utilized.
The conserved recipient's right ventricle
provides the necessary assistance to the
transplanted heart to overcome significant
pulmonary hypertension.
30
  • The incidence of tricuspid regurgitation is
    reported to be as high as 47-98 following heart
    transplantation (Chan, 2001).
  • Some centers have now begun to prophylactically
    perform tricuspid annuloplasty on donor grafts
    before performing the transplantation (McGee,
    2004).

31
POSTOPERATIVE MANAGEMENT
  • Because of denervation the SA node of the
    transplanted heart fires at its increased
    intrinsic resting rate of 90 to 110 bpm. The
    allograft relies on distant noncardiac sites as
    its source for catecholamines thus, its response
    to stress (e.g. hypovolemia, hypoxia, anemia) is
    somewhat delayed until circulating catecholamines
    can exert their positive chronotropic effect on
    the heart. Careful examination of the
    electrocardiogram occasionally may reveal a
    distinct P wave originating from the innervated
    atrial remnant of the recipient, and an increase
    in its rate may be used as an early indicator of
    stress. The absence of a normal reflex
    tachycardia in response to venous pooling
    accounts for the frequency of orthostatic
    hypotension in transplant patients.
  • Denervation alters the heart's response to
    therapeutic interventions that act directly
    through the cardiac autonomic nervous system.
    Carotid sinus massage, Valsalva maneuver, and
    atropine have no effect on sinoatrial node firing
    or atrioventricular conduction. Because of
    depletion of myocardial catecholamine stores
    associated with prolonged inotropic support of
    the donor, the allograft often requires high
    doses of catecholamines.
  • ROUTINE HEMODYNAMIC MANAGEMENT
  • Donor myocardial performance is transiently
    depressed in the immediate postoperative period.
    Allograft injury associated with donor
    hemodynamic instability and the hypothermic,
    ischemic insult of preservation contribute to the
    reduced ventricular compliance and contractility
    characteristics of the newly transplanted heart.
    Abnormal atrial dynamics owing to the midatrial
    anastomosis exacerbate the reduction in
    ventricular diastolic loading. An infusion of
    epinephrine or dobutamine is initiated routinely
    in the operating room to provide temporary
    inotropic support. Restoration of normal
    myocardial function usually permits the cautious
    weaning of inotropic support within 2 to 4 days.
  • EARLY ALLOGRAFT FAILURE
  • Early cardiac failure accounts for up to 25 of
    perioperative deaths of transplant recipients.
    The cause may be multifactorial, but the most
    important etiologies are pulmonary hypertension,
    ischemic injury during preservation, and acute
    rejection. Mechanical support with an
    intra-aortic balloon pump or ventricular assist
    device is indicated in cases refractory to
    pharmacologic interventions. Re-transplantation
    in this setting is associated with very high
    mortality.
  • Chronic left ventricular failure frequently is
    associated with elevated pulmonary vascular
    resistance, and the unprepared donor right
    ventricle may be unable to overcome this
    increased afterload. Although recipients are
    screened to ensure that those with irreversible
    pulmonary hypertension are not considered for
    transplantation, right heart failure remains a
    leading cause of early mortality. Initial
    management involves employing pulmonary
    vasodilators such as inhaled nitric oxide,
    nitroglycerin, or sodium nitroprusside. Pulmonary
    hypertension refractory to these vasodilators
    will often respond to prostaglandin E1 (PGE1).
    Inhalation nitric oxide is considered the
    standard at several institutions. Intra-aortic or
    pulmonary artery balloon counterpulsation and
    right ventricular assist devices have been
    utilized in patients unresponsive to medical
    therapy.
  • DYSRHYTHMIAS
  • Sinus or junctional bradycardia occurs in more
    than half of transplant recipients. The primary
    risk factor for sinus node dysfunction is
    prolonged organ ischemia. Adequate heart rate is
    achieved with inotropic drug infusions and/or
    temporary epicardial pacing. Most
    bradyarrhythmias resolve over 1 to 2 weeks,
    although recovery may be further delayed in
    patients who received preoperative amiodarone
    therapy. Theophylline has been effective in
    patients with bradyarrhythmias and has decreased
    the need for permanent pacemakers in this patient
    population. Ventricular arrhythmias, primarily
    premature ventricular beats (PVCs) and
    nonsustained ventricular tachycardia, have been
    reported in up to 60 of recipients when
    monitored continuously. AF/flutter is treated
    with digoxin, but at a higher dose than used in
    the setting of an innervated heart. Arrhythmias
    occasionally are markers for acute rejection.
  • SYSTEMIC HYPERTENSION
  • Mean arterial pressures greater than 80 mm Hg
    should be treated to prevent unnecessary
    afterload stress on the allograft. In the early
    postoperative period, intravenous sodium
    nitroprusside or nitroglycerin is administered.
    Nitroglycerin is associated with less pulmonary
    shunting because of a relative preservation of
    the pulmonary hypoxic vasoconstrictor reflex. If
    hypertension persists, an oral antihypertensive
    can be added to permit weaning of the parenteral
    agents.

32
  • Respiratory Management
  • The respiratory management is the same as
    following routine cardiac surgery.
  • Renal Function
  • Preoperative renal insufficiency owing to
    chronic heart failure and the nephrotoxic effects
    of cyclosporine places the recipient at increased
    risk of renal insufficiency. Acute
    cyclosporine-induced renal insufficiency usually
    will resolve with the reduction in cyclosporine
    dose. Patients at risk for renal failure
    initially may receive cyclosporine as a
    continuous intravenous infusion to eliminate the
    wide fluctuations in levels associated with oral
    dosing. Furthermore, concurrent administration of
    mannitol with cyclosporine may reduce its
    nephrotoxicity. Alternatively, some centers
    administer a cytolytic agent in the immediate
    postoperative period and delay the initiation of
    cyclosporine therapy.
  • Intermediate Care Unit and Convalescent Ward
  • The increasing risk of nosocomial infections
    with resistant organisms has led to shorter
    hospital stays for cardiac transplant recipients.
    Most patients are discharged 7 to 14 days
    following transplantation. Patient education is
    performed by the cardiac nursing staff. Topics
    include medications (regimens and potential side
    effects), diet, exercise (routines and
    restrictions), and infection recognition.
  • Outpatient Follow-up
  • Close follow-up by an experienced transplant
    team is the cornerstone for successful long-term
    survival after cardiac transplantation. This
    comprehensive team facilitates the early
    detection of rejection, opportunistic infections,
    patient noncompliance, and adverse sequelae of
    immunosuppression. Clinic visits routinely are
    scheduled concurrently with endomyocardial
    biopsies and include physical examination, a
    variety of laboratory studies, CXR and ECG.

33
IMMUNOSUPPRESSIVE THERAPY
  • An organism's ability to distinguish self from
    non-self is critical for its survival in a
    hostile environment. In transplantation, the
    recipient's host defense mechanisms recognize the
    human leukocyte antigens (HLA) on allograft cells
    as being non-self and, if permitted, will respond
    to eradicate the foreign cells.
  • The ultimate goal of immunosuppressive therapy is
    the selective modulation of the recipient's
    immune response to prevent rejection, whilst
    sparing immune defenses against infections or
    neoplasia and minimizing the toxicity associated
    with immunosuppressive agents

34
Pharmacologic Immunosuppressive Strategies
  • Early induction phase followed by a long-term
    maintenance phase. This basic strategy
    essentially is universal, although the choice of
    immunosuppressive agents, dosages, and
    combination protocols vary among transplantation
    centers.
  • Tendency for allograft rejection is greatest in
    the early postoperative period the most intense
    immunosuppression is administered during this
    induction phase. Most programs employ a triple
    immunosuppressive regimen while some centers also
    provide additional induction prophylaxis with
    potent polyclonal antibodies, and OKT3 or IL-2
    blockers.
  • After several months, immunosuppression and
    rejection surveillance are gradually reduced to
    chronic maintenance phase levels and frequencies.
  • Most centers use triple drug therapy
    cyclosporine, steroids, and mycophenolate
    mofentil or azathioprine. The use of a multidrug
    regimen permits adequate immunosuppression with
    reduced doses of individual agents to minimize
    their toxicity. The use of cyclosporine has
    allowed for steroid-free maintenance
    immunosuppression, thus avoiding the multiple
    untoward sequelae associated with chronic
    corticosteroid therapy immunosuppression.The
    timing of steroid withdrawal varies as some
    clinicians discontinue prednisone within several
    weeks of transplantation, whereas others delay
    the taper until 6 to 12 months posttransplantation
    .
  • Recently, it has been suggested that the majority
    of patients can be completely tapered off
    steroids without an increased incidence of
    rejection. Attempts at corticosteroid withdrawal
    in patients with history of rejection, however,
    have usually been unsuccessful.

35
Hyperacute Rejection
  • Results from pre-formed, donor-specific
    antibodies in the recipient. ABO blood group and
    panel reactive antibody screening have made this
    condition a rare complication.
  • The onset of hyperacute rejection occurs within
    minutes to several hours after transplantation
    and the results are catastrophic.
  • Gross inspection reveals a mottled or dark red,
    flaccid allograft, and histologic examination
    confirms the characteristic global interstitial
    hemorrhage and edema without lymphocytic
    infiltrate.
  • Immunofluorescence techniques reveal deposits of
    immunoglobulins and complement on the vascular
    endothelium.
  • No treatment is effective except
    retransplantation, and even this aggressive
    strategy frequently is unsuccessful.

36
Complications
  • Bleeding from the suture lines is a rare
    occurrence but may require reexploration.
  • Hyperacute rejection can occur immediately after
    blood flow is restored to the allograft and up to
    1 week after surgery despite therapeutic
    immunosuppression.
  • Infection is the primary concern. Preventive
    measures should be instituted. Early on bacterial
    and fungal infections. Fungal infections can
    appear if the patient is diabetic or
    overimmunosuppressed. Prophylaxis for
    Pneumocystis carinii is universally administered,
    as is therapy for CMV infection. Maintain
    vigilance for other uncommon infectious processes
    including Listeria, Legionella, Chlamydia, and
    Nocardia infections.
  • Psychiatric disturbances from steroid therapy can
    occur in the immediate posttransplant period.
    These disturbances may be predicted from the
    pre-transplantation psychiatric evaluation and
    thus averted.
  • Cardiac rejection is to be expected and should be
    detected by endomyocardial biopsy. Depending upon
    the severity of the incident, the process can be
    treated with steroid therapy alone, polyclonal
    antibody therapy, or monoclonal antibody therapy.
  • Allograft vascular disease is the main cause of
    late graft failure and death. The coronary
    arteries develop a progressive concentric
    myointimal hyperplasia. This hyperplasia can
    develop as early as 3 months after
    transplantation. The cause of the process is
    unclear. However, CMV infection and recurrent
    rejection episodes are thought to be associated
    with the cause. Current research indicates that
    the initial ischemia/reperfusion injury of the
    allograft coupled with repeated rejection
    episodes might contribute to the process. The
    only available therapy is re-transplantation. The
    process can sometimes be treated by stenting of
    the diseased vessels.

37
CHRONIC COMPLICATIONS
  • Allograft Coronary Artery Disease
  • Long-term survival of cardiac transplant
    recipients is primarily limited by the
    development of allograft coronary artery disease
    (ACAD), the leading cause of death after the
    first posttransplantation year.343345
    Angiographically detectable ACAD is reported in
    approximately 50 of patients by 5 years after
    transplantation. The etiology of this allograft
    vasculopathy is multifactorial and involves both
    immunologic and nonimmunologic components.
    Recently, it has been shown that immune-related
    risk factors appear to be more significant in the
    development of ACAD.346348 Likewise, many
    nonimmune-associated related risks have been
    implicated in ACAD including increased donor age,
    hyperlipidemia, and CMV infection.349352 These
    immune and nonimmune risk factors lead to unique
    coronary pathology characterized by diffuse,
    concentric intimal proliferation with
    infiltration by smooth muscle cells and
    macrophages leading to narrowing along the entire
    length of the vessel.353354 Furthermore,
    collateral vessels are notably absent. ACAD may
    begin within several weeks posttransplantation
    and insidiously progress at an accelerated rate
    to complete obliteration of the coronary lumen
    with allograft failure secondary to ischemia.355
  • The clinical diagnosis of ACAD is difficult and
    complicated by allograft denervation resulting in
    silent myocardial ischemia. Ventricular
    arrhythmias, congestive heart failure, and sudden
    death are commonly the initial presentation of
    significant ACAD. Noninvasive screening tests
    (e.g., thallium scintigraphy) are unreliable in
    transplant recipients.356 Annual coronary
    angiogram is the current gold standard for ACAD
    surveillance. However, due to the previously
    mentioned pathological changes, it underestimates
    the extent of disease and is insensitive to early
    atherosclerotic lesions.357 This has led to
    growing interest in intravascular ultrasound
    (IVUS) devices.
  • IVUS is better equipped to provide important
    quantitative information regarding vessel wall
    morphology and the degree of intimal
    thickening.358359 Some centers have begun to use
    IVUS for the early detection of ACAD however,
    concerns have been raised concerning its ability
    to assess more long-term lesions.360 Currently,
    the only definitive treatment for advanced ACAD
    is retransplantation due to the diffuse and
    distal nature of ACAD. Based on this lack of
    effective treatment options, an emphasis has been
    placed on prevention of ACAD. Currently,
    prophylactic management focuses on empiric risk
    factor modification (dietary and pharmacologic
    reduction of serum cholesterol, cessation of
    smoking, hypertension control, etc.). Several
    studies have demonstrated a decrease in ACAD in
    patients treated with a calcium channel blocker
    or HMG-CoA reductase inhibitors.348,361
  • Renal Dysfunction
  • Irreversible interstitial fibrosis caused by
    cyclosporine nephrotoxicity is chiefly
    responsible for the chronic renal dysfunction
    observed in cardiac transplant recipients.362363
    Its pathogenesis is unclear but is believed to be
    secondary to afferent arteriolar vasoconstriction
    with secondary ischemia.364365 Direct tubular
    toxicity also may play a contributory role.366
    Most renal injury occurs during the first 6
    months following transplantation concurrent with
    the highest levels of cyclosporine. Little
    additional decline in renal function occurs after
    1 year.367 Frequent monitoring of cyclosporine
    levels and avoidance of intravascular volume
    depletion are important preventive measures.368
    Approximately 3 to10 of patients develop
    end-stage renal failure requiring dialysis or
    renal transplantation.369
  • Hypertension
  • Moderate to severe systemic hypertension afflicts
    50 to 90 of cardiac transplant recipients and
    is a difficult problem to manage. Peripheral
    vasoconstriction in combination with fluid
    retention seem to play the greatest role.
    Although the exact mechanisms are unclear, it
    likely involves a combination of
    cyclosporine-induced tubular nephrotoxicity and
    vasoconstriction of renal and systemic arterioles
    mediated by sympathetic neural activation. No
    single class of antihypertensive agents has
    proven uniformly effective, and treatment of this
    refractory hypertension remains empiric and
    difficult.
  • Malignancy
  • Chronic immunosuppression is associated with an
    increased incidence of malignancy. The estimated
    risk of carcinoma is almost 100-fold greater than
    in the general population
  • Lymphoproliferative disorders and carcinoma of
    the skin are most common. The risk of these
    malignancies is increased further following
    monoclonal and polyclonal antibody therapy There
    is a predilection for unusual extranodal
    locations (e.g., lung, bowel, and brain).
    Treatment options in transplantation include a
    reduction in immunosuppression and high-dose
    acyclovir (to attenuate EBV replication) in
    addition to conventional therapies for carcinoma
    (chemotherapy, radiation therapy, and surgical
    resection).
  • Other
  • Hyperlipidemia eventually develops in the
    majority of recipients and is managed with
    dietary restrictions, exercise, and
    lipid-lowering agents.
  • Osteoporosis
  • Avascular necrosis of weight-bearing joints

38
RESULTS OF OCTx
  • Operative mortality 5 to 10. Primary graft
    failure is the most frequent cause of early
    death. Overall 1-year survival is approx. 80
    with a 4 mortality per year for subsequent
    years.
  • Infection and rejection account for the majority
    of deaths in the first 6 months thereafter,
    accelerated coronary artery disease eventually
    claims the lives of most recipients. Risk factors
    associated with increased mortality include
    ventilator dependence, previous cardiac
    transplantation, preoperative VAD or IABP,
    recipient age greater than 65 years, female
    gender (donor or recipient), and donor age
    greater than 50 years.
  • Health-related quality of life (HRQOL) in
    patients following cardiac transplantation
    demonstrates that most experience a HRQOL that
    approaches that of the normal population.
    Although cardiac reserve is reduced, exercise
    tolerance is improved dramatically compared to
    preoperative level, and recipients usually can
    enjoy an active lifestyle.
  • Nevertheless, because of concerns about future
    disability, recipients often encounter
    significant problems with postoperative
    employment and health insurance coverage
    particularly if over 50 years of age.

39
CARDIAC RE-TRANSPLANTATION
  • Re-transplantation accounts for fewer than 3 of
    the cardiac transplants. Primary indications
    allograft coronary artery disease and refractory
    acute rejection.
  • Actuarial survival remains markedly reduced
    following re-transplantation if performed within
    6 months of the initial procedure or in the
    setting of acute rejection. Recent data suggest
    that the survival rate for cardiac
    re-transplantation at 1 year is 55.
  • Recent data from the International Society for
    Heart and Lung Transplantation (ISHLT) also shows
    though that if re-transplantation occurs 2 years
    after the initial transplant procedure, the
    1-year survival rate markedly improves but
    remains approximately 4 to 6 below that of
    primary cardiac transplantation.

40
FUTURE 
  • Clinical outcome of heart transplantation has
    dramatically improved. Although cardiac
    replacement remains the best therapeutic option
    for patients with end-stage heart failure, a
    number of challenges await future investigators
    to further improve survival and reduce
    transplant-related morbidity.
  • A major factor limiting long-term survival of
    recipients is allograft rejection and the
    untoward effects of immunosuppression.
    Development of reliable, noninvasive diagnostic
    studies will permit more frequent evaluations for
    the early detection of rejection and for
    monitoring the effectiveness of therapy.
    Ultimately, this will allow more precise control
    of immunosuppression, and in turn a reduction in
    cumulative allograft injury and infectious
    complications.
  • Immunosuppressive strategists will continue their
    efforts to establish specific unresponsiveness to
    antigens of transplanted organs in hopes of
    preserving much of the recipient's immune
    responses. Novel immunosuppressive agents and
    techniques are under continuous investigation for
    this purpose. Alternatively, donor organs may be
    made less susceptible to immunologic attack
    through genetic engineering techniques by
    altering the expression of cell membrane-bound
    molecules. This approach is being currently
    utilized in the pursuit of clinically applicable
    xenotransplant sources.
  • Xenografts eventually may be an additional source
    of donor organs, although extended xenograft
    survival remains an elusive goal. Complicating
    this alternative are unresolved ethical issues
    concerning transgenic experimentation and the
    potential for transmission of veterinary
    pathogens to an immunosuppressed recipient.
  • Future improvements in organ preservation
    permitting extension of the storage interval will
    have several benefits. In addition to a modest
    increase in the donor pool, extension of storage
    times would permit better allocation of organs
    with respect to donor-recipient immunologic
    matching. There is growing evidence that human
    lymphocyte antigen (HLA) matching may be
    important for long-term graft function through
    attenuation of chronic rejection. Reducing the
    ischemic injury may also result in an attenuation
    of transplant coronary artery disease.
  • Mechanical assist devices are being used more
    frequently in patients with end-stage heart
    failure and may prove to be the best solution for
    the current organ shortage. Assist devices are
    being currently used both as a bridge to
    transplantation and a destination therapy. The
    Randomized Evaluation of Mechanical Assistance
    for the Treatment of Congestive Heart Failure
    (REMATCH) study demonstrated a survival benefit
    in heart failure patients in which assist devices
    were utilized versus all other forms of treatment
    for heart failure.61 It appears that as the
    technology of assist devices continues to
    improve, it is only a matter of time before they
    become a long-term solution for patients with
    severe congestive heart failure.

41
History heart-lung and lung transplantation
  • First lung transplantation James Hardy 1963. But
    it took another 20 years before routine.
  • First Heart-Lung transplantation Demikhov in dogs
    1962, Reitz 1981 human
  • Initial graft failure secondary to
  • inadequate preservation
  • long ischaemic times
  • lack of good immuno-suppressive drugs
  • technical difficulties with bronchial anastomoses

42
  • En-bloc double lung replacement introduced by
    Patterson in 1988. This technique was later
    replaced by sequential bilateral lung
    transplantation, by Pasque in 1990.
  • More recent operative innovations include living
    lobar transplantation, an alternative to
    cadaveric bilateral lung transplantation.
  • Combined heart-lung and isolated lung
    transplantation have emerged as lifesaving
    procedures for patients with end-stage
    cardiopulmonary or pulmonary disease.
  • To date, 2861 combined heart-lung transplants,
    7204 single lung transplants, and 5420 bilateral
    lung transplants have been performed worldwide.
    While the number of heart-lung transplants
    performed annually has declined in recent years,
    the number of single and bilateral lung
    transplantation procedures remains stable.

43
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44
Indications HLTx
45
Indications for single and bilateral lung
transplantation
46
Contra-indications to HLTx and LTx
  • Age gt 50 (heart-lung), gt 55 (bilateral lung), gt
    60 (single lung)
  • Significant systemic or multisystem disease
    (e.g., peripheral or cerebrovascular disease,
    portal hypertension, poorly controlled diabetes
    mellitus)
  • Significant irreversible hepatic or renal
    dysfunction (e.g., bilirubin gt 3.0 mg/dL,
    creatinine clearance lt 50 mg/mL/min)
  • Active malignancy
  • Corticosteroid therapy (gt 10 mg/day)
  • Panresistant respiratory flora
  • Cachexia or obesity (lt 70 or gt 130 ideal body
    weight)
  • Current cigarette smoking
  • Psychiatric illness or history of medical
    noncompliance
  • Drug or alcohol abuse
  • Previous cardiothoracic surgery (considered on a
    case-by-case basis)
  • Severe osteoporosis
  • Prolonged mechanical ventilation
  • HIV or HBsAg positivity
  • Hepatitis C infection with biopsy-proven liver
    disease

47
Recipient selection HLTx and LTx
  • Progressively disabling cardiopulmonary or
    pulmonary disease who still possess the capacity
    for full rehabilitation after transplantation..
  • Life expectancy of less than 18 to 24 months
    despite the use of appropriate medical or
    alternative surgical strategies. On average,
    waiting times can be from 6 to 36 months.
    Unfortunately, mortality while on the waiting
    list remains nearly 20 for both lung and
    heart-lung transplant candidates.
  • Disabling symptoms prompting consideration for
    transplantation typically include dyspnea,
    cyanosis, syncope, and haemoptysis. NYHA classes
    III or IV.
  • Evaluation includes a complete history, physical
    examination, laboratory tests, specialized
    studies, and a psychosocial evaluation.

48
Tests and studies recipient evaluation HLTx and
LTx
  • Laboratory tests and studies    routine
    haematology including clotting, blood type and
    antibody screen, Immunology panel (FANA, RF),
    UE, LFTs    Electrolytes, including Mg2     CK
    with isoenzymes    Serum protein
    electrophoresis    Urinalysis    Viral
    serologies        Compromised host panel
    (cytomegalovirus, adenovirus, varicella-zoster,
    herpes simplex, Epstein-Barr virus)        Hepatit
    is A, B, and C antibodies, hepatitis B surface
    antigen (HBsAg)        Cytomegalovirus
    (quantitative antibodies and IgM) Human
    immunodeficiency virus    Electrocardiogram    Che
    st x-rayStudies obtained as indicated    Echocardi
    ogram with bubble study    MUGA for right and
    left ventricular ejection fraction    Cardiac
    catheterization with coronary angiogram    Thoraci
    c CT scan    Quantitative ventilation-perfusion
    scans    Carotid duplex    Mammogram    Sputum
    for Gram stain, AFB smear, KOH, and routine
    bacterial, mycobacterial, and fungal cultures
  • Required for listing (phase II)HLA and DR typing
  • Transplant antibody
  • Quantitative immunoglobulins
  • Histoplasma, Coccidiodes, and Toxoplasma titers
    PPD
  • Pulmonary function tests with arterial blood
    gases
  • 12-hour urine collection for creatinine clearance
    and total protein
  • Urine viral culture

49
  • It is extremely important that a candidate's
    medical condition be optimized prior to
    heart-lung and lung transplantation. Standard
    medical measures should be aggressively employed
    by the patient's local physician, and the patient
    should have routine follow-up at the transplant
    center.
  • Supplemental oxygen is recommended for any
    patient exhibiting arterial hypoxemia, defined as
    either an arterial oxygen saturation less than
    90 or an arterial Po2 less than 60 mm Hg at
    rest, during exertion, or while asleep.
  • For patients with heart failure, standard
    therapeutic measures are applied, including
    dietary restrictions, diuretics, and
    vasodilators. Dietary water and salt restriction
    as well as diuretic therapy facilitate
    intravascular fluid management. However,
    particular care must be exercised when using loop
    diuretics in patients with underlying pulmonary
    disease this class of potent diuretics results
    in a metabolic alkalosis that depresses the
    effectiveness of carbon dioxide as a stimulus for
    breathing. Vasodilators result in afterload
    reduction, and have been proven to effectively
    improve functional capacity and prolong survival
    in patients suffering from severe cardiac
    failure.Commonly used vasodilators include
    nitrates, hydralazine, and angiotensin-converting
    enzyme inhibitors.
  • Despite the clinical heterogeneity among patients
    with primary pulmonary hypertension, conventional
    medical therapy targets the sequelae of the
    pulmonary vascular derangements associated with
    this disease process. Supplemental oxygen therapy
    is recommended to eliminate the stimulus for
    hypoxic pulmonary vasoconstriction and secondary
    erythropoiesis, thus lessening the burden placed
    on the right side of the heart and diminishing
    the likelihood of cardiac arrhythmias. Pulmonary
    vasodilator therapy is important in the treatment
    of primary pulmonary hypertension, and includes
    the use of calcium channel blockers and
    continuous prostacyclin infusions. Because most
    standard vasodilators have potent systemic
    effects, careful dosing and follow-up is
    essential. Approximately 20 of patients with
    primary pulmonary hypertension will respond to
    calcium channel blockers, and this favorable
    response can usually be predicted by the response
    to short-acting vasodilators during cardiac
    catheterization, but response to the acute
    vasodilator challenge does not always predict the
    response to long-term prostacyclin infusion.
  • Interstitial lung disease in patients awaiting
    transplantation results from a wide variety of
    diffuse inflammatory processes, such as
    sarcoidosis, asbestosis, and collagen-vascular
    diseases. Increases in pulmonary vascular
    resistance leading to right-sided heart failure
    are thought to result from interstitial
    inflammatory infiltrates that entrap and
    eventually destroy septal arterioles, reducing
    the distensibility of the remaining pulmonary
    vessels.This process, coupled with closure of
    peripheral bronchioles, results in arterial
    hypoxemia, which further aggravates pulmonary
    hypertension. Corticosteroids are the mainstay of
    treatment in this class of diseases. The adverse
    effects of steroids on airway healing are well
    established, and mandate significant dose
    reductions in anticipation of heart-lung and
    isolated lung transplantation.
  • The multisystem manifestations of cystic
    fibrosis, particularly chronic bronchopulmonary
    infection, malabsorption, malnutrition, and
    diabetes mellitus, pose difficult management
    problems and require aggressive chest
    physiotherapy, antibiotics, enteral or parenteral
    nutritional supplementation, and tight serum
    glucose control.
  • Certain underlying diagnoses are associated with
    increased rates of pulmonary and systemic
    thrombosis and embolization. These include
    dilated cardiomyopathy, congestive heart failure,
    and primary pulmonary hypertension, and most
    centers recommend routine prophylactic
    anticoagulation with heparin, warfarin, or
    antiplatelet agents.

50
HLTx and LTx donor selection criteria
  • lt 40 (heart-lung), lt 50 (lung)
  • Smoking history less than 20 pack-years
  • Arterial Po2 of 140 mm Hg on an Fio2 of 40 or
    300 mm Hg on an Fio2 of 100
  • Normal chest x-ray
  • Sputum free of bacteria, fungus, or significant
    numbers of white blood cells on Gram and fungal
    staining
  • Bronchoscopy showing absence of purulent
    secretions or signs of aspiration
  • Absence of thoracic trauma
  • HIV negative

51
Donor Management
  • Maintenance of haemodynamic stability and
    pulmonary function. Patients suffering from acute
    brain injury are often haemodynamically unstable
    due to neurogenic shock, exc
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