Transcript heart transplantation

HEART
TRANSPLANTATION
According to ACC/AHA guidelines the only established surgical treatment for advanced heart failure is cardiac transplantation.
1yr survival>85%
5yr survival>70%
ACC/AHA Classification :
STAGE
DESCRIPTION
A ; High risk for heart failure
HTN; DM; CAD ;family h/o cardiomyopathy
B; Asymptomatic heart failure
C ; symptomatic heart failure
previous MI; LV dysfunction ; valvular heart dis.
structural heart dis; dyspnea; fatigue; impaired
Exercise tolerance
D; Refractory endstage heart failure
marked sym at rest despite maximal medical
therapy
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NYHA heart failure symptom classification system –
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1-ordinary physical activity not limited by
symptom
2- ordinary physical activity somewhat
limited by dyspnea
3- exercise limited; dyspnea during mild work
4- dyspnea at rest/ very little exertion
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M.C Indications for cardiac transplantation ;
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-Idiopathic or ischemic cardiomyopathy
- postpartum cardiomyopathy
- refractory valvular heart disease
- primary myocardial disease- amyloidosis; sarcoidosis
- drug induced myocardial disease
- congenital heart disease
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INVESTIGATIONS
-history/physical examination
-Routine haematological testing
- serum biochemistry/ electrolytes
- viral testing
- ECG
- Echocardiography
- chest x ray pa view
- rt and left heart catheterization
- PFTs
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GOAL of evaluation is to confirm a diagnosis of class D heart failure that has been maximally treated but will
result in death in <1yr.
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-UNOS (United Network for Organ Sharing)
UNOS selection guidelines ------A--- priority to patients with endstage HF and life expectancy <1yr such as pts in cardiogenic shock or low output
states requiring mech/ ionotropic support
B---- Advanced symptomatic heart failure and peak oxygen uptake<10 ml/kg/min with achievement of anaerobic
threshhold
C---- NYHA class 4 ( d/t advanced hypertrophic and restrrictive cardiomyopathy)
D----refractory angina with inoperable CAD
E-----life threatning ventricular arrhythymias
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Assessing PVR and Reversibility ---------Pts with ischemic or idiopathic cardiomyopathy and inc LAP often have reversible PVR a condition usually reverses
after 1st wk of transplantation.
UNOS allocates donor heart according to each pts priority status , ABO group, body size match, distace from
donor centre,
---highest priority is given to inpatients supported by mechanical circulatory assist devices for acute hemodynamic
decompensation
---- pts requiring continuous infusion of single or multiple high dose iv ionotropes
---- those with life exp,of < 7 days without transplantation
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DONOR accepted after---------Echocardiograhy which assesses LV fn, valve function, segmental and global wall motion abn. , mild LV
hypertrophy acceptable , MVP acceptable
--- coronary angiography
---- determination of hypotension,hypoxia and tissue trauma after confirmation of brain death and organ viability
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ANAESTHETISTS main concern is to
maintain hemodynamic stability : SBP> 100mmHg ; CVP 8-10mmHg
ABG- Nr with PaO2>100mmHg
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DONOR-------Median sternotomy—evaluate myocardial function and inspect
heart for abnormalities----systemic heparinization
 (300u/kg)---SVC ligated and IVC transected---aorta cross
clamped,heart decompressed and cold(4degc) cardioplegia
solution infused---heart removed and prepared for transport
by placing in sterile plastic bag that is placed inside another
bag filled with ice cold saline-- Package is carried in ice chest
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Upper time limit b/w harvesting and reimplantation of heart is
approx 6hrs
 Induction should be timed so that CPB can commence
immediately on arrival of donor heart
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ORTHOTROPIC HEART TRANSPLANTATION :
Median sternotomy
Groin prepared and draped to provide rapid route for CPB
cannulation should it become necessary---Pericardial incision--Heparin 300u/kg is administered--- cannulation of ascending aorta
and venacava via RA--- CPB initiated--- Hypothermia instituted--Native heart incised at midlevel of atria---Donor and Native left
atria anastomosed just followed by Rt atria . Commonly SVC & IVC
are anastomosed directly& LA is excised down to entry of pulmonary
veins--- dose of methylprednisolone & ATG given
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If donor heart fails to maintain Nr rhythm– electrical cardioversion,
iv chronotropic, ionotropic
Slow HR—isoproterenol,dobutamine, temporary pacing
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COMPLICATIONS during weaning :
1- RV failure– RV hypokinesis,RV distension on TEE,inc CVP,inc PAP.
Donor heart is not able to face acutely elevated RV afterload.
Cause—preexisting pul HTN
Transient pul. Vasospasm
Tricuspid/pulmonary valve insufficiency
Donor recipent size mismatch
Intracoronary air emboli
Prolonged donor heart ischemia
Inadequate myocardial protection
Treatment---Ionotropic support- isoproterenol/dobutamine
Therapy for pul. Vasodilation--PDE inhibitor-milrinone
PGE1
Nesiritide
Inhaled PGI2 ( Epoprostenol )
Inhaled Nitric Oxide
Vasopressin preserves SVR without causing significant changes in PVR --- Used to maintain RV
perfusion pressures
Pt may require support with RV assist devices.
LUNG TRANSPLANTATION
History and Epidemiology
 Although the first human lung transplant was
performed in 1963, surgical technical problems
and inadequate preservation and
immunosuppression regimens prevented
widespread acceptance of this procedure until
the mid 1980s .Advances in these areas have
since made lung transplantation a viable option
for many patients with end-stage lung disease.
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Infection is the most frequent cause of death in the first
year after transplant, but this is superceded in later
years by bronchiolitis obliterans.
Some of the most challenging patients are those with
cystic fibrosis. The 1-year survival of 79% and 5-year
survival of 57% after lung transplantation have shown
that despite the high incidence of poor nutrition and the
almost ubiquitous colonization by multidrug-resistant
organisms, these patients can still successfully undergo
lung transplantation with acceptable outcome data.[
Recipient Selection
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candidates should be terminally ill with end-stage lung
disease (NYHA class III or IV, with a life expectancy of
approximately 2 years), be psychologically stable, and be
devoid of serious medical illness (especially
extrapulmonary infection) compromising other organ
systems. Patients already requiring mechanical
ventilation are poor candidates, although lung
transplantation can be successful in such a setting. Other
factors such as advanced age, previous thoracic surgery
or deformity, and corticosteroid dependence may be
regarded as relative contraindications by individual
transplant centers. Hepatic disease due solely to rightsided heart dysfunction should not preclude candidacy.
ASSESMENT OF SUITABILITY
Pulmonary spirometery
 Chest X-ray & CT
 Echocardiography
 MUGA scan
 Left heart catheterization—in patients of
PAH
 TEE
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Donor Selection and Graft
Harvest
CT has been used to assess the structural
integrity of the lung, particularly in donors
who have sustained traumatic chest injury.
 Lungs that have contusion limited to less
than 30% of a single lobe can be
considered adequate.[
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The lungs are matched to the recipient for
ABO blood type and size (oversized lungs
can result in severe atelectasis and
compromise of venous return in the
recipient, especially after double-lung
transplantation). Donor serology and
tracheal cultures guide subsequent
antibacterial and antiviral therapy in the
recipient.
Graft Harvest
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The heart is removed as described for heart transplantation, using
inflow occlusion and cardioplegic arrest, with division of the IVC and
SVC, the aorta, and the main PA. Immediately after cross-clamping,
the pulmonary vasculature is flushed with ice-cold preservative
solution, which often contains prostaglandin E1. This is believed to
promote pulmonary vasodilation, which aids homogeneous
distribution of the preserving solution. Other additives that have
been included are nitroglycerin and low-potassium 5% Dextran. The
LA is divided so as to leave an adequate LA cuff forboth the heart
graft and lung graft(s) with the pulmonary veins. After explanation,
the lung may also be flushed to clear all pulmonary veins of any
clots. After the lung is inflated, the trachea (or bronchus for an
isolated lung) is clamped, divided, and stapled closed. Inflating the
lung has been shown to increase cold ischemia tolerance of the
donor organ. The lung graft is removed, bagged, and immersed in
ice-cold saline for transport.
Warm Pulmonoplegia
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Hematocrit 18% to 20%, leukocyte depleted
L-glutamate
L-aspartate
Adenosine
Lidocaine
Nitroglycerine
Verapamil
Dextrose
insulin
Surgical Procedures
single-lung transplantation is the
procedure of choice for all lung transplant
candidates.
 Double lung transplantation is generally
done in cystic fibrosis, bronchiactasis and
patients with severe air trapping
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Single-Lung Transplant
The recipient is positioned for a posterolateral
thoracotomy, with the ipsilateral groin prepped
and exposed in case CPB becomes necessary.
 With the lung deflated, a pneumonectomy is
performed, with special care to preserve as long
a PA segment as possible.
 After removal of the diseased native lung, the
allograft is positioned in the chest with
precautions to maintain its cold tissue
temperature.
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The bronchial anastomosis is performed first.
The PA is anastomosed next.
Pericardium is opened and the allograft LA cuff
containing the pulmonary venous orifices is
anastomosed to the native LA.
 The pulmonary circuit is then flushed with blood
and de-aired. The initial flush solution is usually
cold (4°C) but is followed by a warm (37°C)
flush. The warm flush is usually performed
during final completion of the vascular
anastomoses.
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Glucocorticoid administration, the vascular
clamps are removed, reperfusion is begun,
and the lung reinflated with a series of
ventilations to full functional residual
capacity.
 Chest tubes are placed, the wound is
closed, and the patient is transported to
the ICU.
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Double-Lung Transplant
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Transplantation of both lungs is performed in the
supine position.
Two types of approaches
-Median sternotomy
-Clamshell thoracosternotomy
Recipient pneumonectomy and implantation of
the donor lung are performed sequentially on
both lungs in essentially the same manner as
described above for a single-lung transplant. The
native lung with the worst function should be
transplanted first.
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2
LEFT Ventricular dysfunction----d/t - prolonged donor heart ischemia
-Inadequate myocardial protection
-coronary air embolization
-inadequate myocardial perfusion
Rx- high dose ionotrope
Epinephrine,milrinone,vasopressin
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d/t
COAGULOPATHY
hepatic congestion ( chronic )
Haemodilution
Hypothermia
CPB circuit
Rx –
FFP
Fresh blood/ cryoprecipitates
Platelets, Factor 7
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Transplanted heart lacks autonomic control of ionotropy/ chronotropy d/t autonomic denervation
Isoproteronol
Dobutamine
Epinephrine
Cardiac pacing
In patients whose indication for transplantation
is suppurative disease, the pleural cavity is
pulse-lavaged with antibiotic-containing solution
that has been tailored to that patient's
antimicrobial sensitivity profile.
 The anesthesiologist irrigates the trachea and
bronchi with diluted iodophore solution before
the donor lung is brought onto the surgical field.
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Pathophysiology before
Transplantation
Patients with highly compliant lungs and obstruction of
expiratory airflow cannot completely exhale the delivered
tidal volume, resulting in positive intrapleural pressure
throughout the respiratory cycle (“auto-PEEP” [positive
end-expiratory pressure] or “intrinsic PEEP”), which
decreases venous return and causes hypotension.
 The presence of auto-PEEP is highly negatively
correlated with FEV1 (percent predicted) and highly
positively correlated with pulmonary flow resistance and
resting hypercarbia.
 Hyperinflation is a frequent complication of single-lung
ventilation during lung transplantation in patients with
obstructive lung disease.
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Hyperinflation can be ameliorated with
deliberate hypoventilation
 PEEP may also decrease air trapping
because it decreases expiratory resistance
during controlled mechanical ventilation.
However, the application of PEEP requires
close monitoring, because if the level of
extrinsic PEEP applied exceeds the level of
auto-PEEP, further air trapping may result.
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RV failure
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RV failure is frequently encountered in
lung transplant recipients with pulmonary
hypertension due to chronically elevated
RV afterload. The response of the RV to a
chronic increase in afterload is to
hypertrophy, but eventually this adaptive
response is insufficient. As a result, RV
volume decreases and chamber dilation
results.
Treatment of Intraoperative Right
Ventricular Failure
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Avoid large increases in intrathoracic pressure from:
Positive end-expiratory pressure (PEEP)
Large tidal volumes
Inadequate expiratory time
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Intravascular volume
Increase preload if pulmonary vascular
resistance is normal.
Rely on inotropes (dobutamine) if pulmonary vascular resistance is
increased.
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Maintain right ventricular coronary perfusion pressure with α-adrenergic
agonists.
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Cautious administration of pulmonary vasodilators (avoid systemic and
gas exchange effects)
Prostaglandin E1 (0.05 to 0.15 μg/kg/min)
Inhaled nitric oxide (20 to 40 ppm)
Pathophysiology after Lung
Transplantation
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In single-lung recipients, the pattern of ventilation-perfusion
matching depends on the original disease process. For example,
with pulmonary fibrosis, blood flow and ventilation gradually divert
to the transplanted lung, whereas in patients transplanted for
diseases associated with pulmonary hypertension, blood flow is
almost exclusively diverted to the transplanted lung, which still
receives only half of the total ventilation. In such patients the native
lung represents mostly deadspace ventilation.
Transplantation results in obligatory sympathetic and
parasympathetic denervation of the donor lung and therefore alters
the physiologic responses of airway smooth muscle. Exaggerated
bronchoconstrictive responses to the muscarinic agonist
methacholine have been noted in some studies of denervated lung
recipients.
The mechanism of hyperresponsiveness
may involve cholinergic synapses,
inasmuch as they are the main mediators
of bronchoconstriction.
 Enhanced release of acetylcholine from
cholinergic nerve endings due to an
increased responsiveness of
parasympathetic nerves or else loss of
inhibitory innervation.
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Mucociliary function is transiently severely impaired after lung
transplantation and remains depressed for up to 1 year after the
procedure. Thus, transplant recipients require particularly aggressive
endotracheal suctioning to remove airway secretions.
Lung transplantation also profoundly alters the vascular system. The
ischemia and reperfusion that are an obligatory part of the
transplantation process damage endothelia. Cold ischemia alone
decreases β-adrenergic cyclic adenosine monophosphate (cAMP)mediated vascular relaxation by approximately 40%, and
subsequent reperfusion produces even greater decreases in both
cyclic guanosine monophosphate (cGMP)-mediated and β-adrenergic
cAMP-mediated pulmonary vascular smooth muscle relaxation.
Endothelial damage in the pulmonary allograft
also results in “leaky” alveolar capillaries and the
development of pulmonary edema.
 Alterations in the response of denervated
pulmonary vasculature to α1-adrenergic agents
and prostaglandin E1, as well as a reduction in
nitric oxide activity.
 Dysfunctional responses to mediators may be
exaggerated if CPB is required.
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Pulmonary vascular resistance can be
substantially decreased with the
administration of inhaled nitric oxide after
reperfusion.
 Nitric oxide prevents or modulates
reperfusion injury as measured by
decreased lung water, lipid peroxidase
activity, and neutrophil aggregation in the
graft.
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PA pressures decrease dramatically during lung
transplantation in patients who had pulmonary
hypertension before transplantation and remain
so for weeks to months thereafter. Concomitant
with the decrease in PA pressure, there is an
immediate decrease in RV size after lung
transplantation in those patients with preexisting
pulmonary hypertension, as well as a return to a
more normal geometry of the interventricular
septum. Both of these effects are sustained over
several weeks to months.
Anesthetic Management
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Preoperative Evaluation and Preparation
- History and physical examination
- The time and nature of the last oral
intake
- Evaluation of the airway for ease of
laryngoscopy and intubation
- The presence of any reversible pulmonary
dysfunction such as bronchospasm; and signs of
cardiac failure.
- Evaluation of the chest radiograph
Equipments
Double lumen endobronchial tubes offer the
advantages of easy switching of the ventilated
lung, suctioning of the nonventilated lung, and
facile independent lung ventilation
postoperatively. A left-sided double-lumen
endobronchial tube is suitable for virtually all
lung transplant cases (even left lung
transplants).
 A fiberoptic bronchoscope is absolutely required
to rapidly and unambiguously verify correct tube
positioning, evaluate bronchial anastomoses,
and clear airway secretions.
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A ventilator with low internal compliance is necessary to adequately
ventilate the noncompliant lungs of recipients with restrictive lung
disease or donor lungs with reperfusion injury.
Single-lung recipients with highly compliant lungs may require
independent lung ventilation with a second ventilator after
transplantation.
A PA catheter capable of estimating RV ejection fraction (RVEF) can
be useful in diagnosing RV failure and its response to inotropes and
vasodilators.
A rapid infusion system can be lifesaving in patients in whom major
hemorrhage occurs due to anastomotic leaks, inadequate surgical
ligation of mediastinal collateral vessels, chest wall adhesions, or
coagulopathy after CPB.
Induction
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Judicious use of intravenous benzodiazepines or
narcotics.
Noninvasive monitoring
Intravenous access
Continuous monitoring via a fiberoptic electrode placed
in the arterial catheter may occasionally be useful if this
technology is available. The femoral artery should be
avoided if possible because the groin may be needed as
a site for cannulation for CPB.
A TEE probe is placed after the airway is secured.
Three main principles should guide the
formulation of a plan for induction:
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(1) protection of the airway;
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(2) avoidance of myocardial depression and
increases in RV afterload in patients with RV
dysfunction; and
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(3) avoidance and recognition of lung
hyperinflation in patients with increased lung
compliance and expiratory airflow obstruction
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All lung transplants are done on an emergency basis,
and the majority of patients will have recently had oral
intake and must be considered to have “full stomachs.”
conventional rapid-sequence intravenous induction with
a short-acting hypnotic (e.g., etomidate 0.2 to 0.3
mg/kg), a small amount of narcotic (e.g., up to 10 μg/kg
of fentanyl), and succinylcholine will usually be tolerated.
Once the trachea is intubated and positive-pressure
ventilation initiated, the avoidance of hyperinflation in
patients with increased pulmonary compliance or bullous
disease is crucial. Small tidal volumes and low
respiratory rates and inspiratory/expiratory (I/E) ratios
should be used (“permissive hypercapnia”).
Intraoperative Management
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Tidal volume and respiratory rate
• Maintain in patients with normal or decreased lung compliance (i.e., primary pulmonary
hypertension, fibrosis)
• Decrease both tidal volume and rate in patients with increased compliance (e.g.,
obstructive lung disease) to avoid hyperinflation (“permissive hypercapnia”)
Maintain oxygenation by
• 100% Inspired oxygen
• Applying continuous positive airway pressure (5 to 10 cm) to nonventilated lung
• Adding positive end-expiratory pressure (5 to 10 cm) to ventilated lung
• Intermittent lung re-inflation if necessary
Surgical ligation of the pulmonary artery of the nonventilated lung
Be alert for development of pneumothorax on nonoperative side
• Sharp drop in oxygen saturation, end-tidal carbon dioxide
• Sharp rise in peak airway pressures
• Increased risk with bullous lung disease
Therapy
• Relieve tension
• Resume ventilation
• Emergency cardiopulmonary bypass
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Indications for Cardiopulmonary Bypass
during Lung Transplantation
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Cardiac index<2 L/min/m2
Svo2 <60%
Mean arterial pressure<50 to 60 mmHg
Sao2<85% to 90%
pH<7.00
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Patients with severe pulmonary hypertension (greater
than two thirds of systemic pressure) will generally be
placed on CPB before PA clamping. The intraoperative
use of nitric oxide (20 to 40 ppm) may allow some
procedures to proceed without the use of CPB.
CPB may provide very stable hemodynamics, it is
associated with an increased transfusion requirement. In
addition, graft function (as reflected by alveolar-arterial
oxygen gradient) may be compromised, endotheliumdependent cGMP- and β-adrenergic cAMP-mediated
pulmonary vascular relaxation may be impaired to a
greater degree, and a longer period of mechanical
ventilation may be necessary.
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Exceptional circumstances require CPB: the presence of severe
pulmonary hypertension, because clamping of the PA will likely
result in acute RV failure and “flooding” of the nonclamped lung; the
repair of associated cardiac anomalies (e.g., patent foramen ovale,
atrial or ventricular septal defects); treatment of severe
hemodynamic or gas exchange instabilities; and living-related lobar
transplantation.
Extracorporeal membrane oxygenation (ECMO) has also been
suggested as an alternative method of CPB during lung
transplantation.
The use of ECMO with heparin-bonded circuits might improve the
outcome of both single- and double-lung transplants by lessening
the amount of pulmonary edema,decreased transfusion
requirements, reperfusion of the lungs can be more easily controlled
since the CO transiting the newly transplanted lung can be precisely
controlled. This is especially the case for patients with advanced
pulmonary hypertension.
During weaning special attention should be
directed to assessing and supporting RV function
during this period.
 Coagulopathy after weaning from CPB is
common.
 Coagulopathy is treated by platelets , FFP.
 Reperfusion without CPB is often accompanied
by a mild to moderate decrease in systemic
blood pressure and occasionally is complicated
by severe hypotension.
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Some degree of pulmonary edema is commonly detected by chest
radiography postoperatively, it is uncommon to encounter severe
pulmonary edema in the operating room immediately after
reperfusion of the graft.
When developing in operating room it is life threatening and should
be treated by--High level of PEEP using selective lung ventilation,
diuresis, and volume restriction. Occasionally, patients may require
support with ECMO for several days until reperfusion injury resolves;
a high percentage of patients so treated ultimately survive.
Adequate analgesia is crucial for these patients to facilitate the
earliest possible extubation, ambulation, and participation in
spirometric exercises to enhance or preserve pulmonary function.
Pneumothorax must be a constant concern for
the anesthesiologist.
 Transient cessation of ventilation and immediate
fiberoptic bronchoscopy .
 If this diagnosis is strongly suspected, needle
thoracostomy on the field may be lifesaving.
Alternatively, the surgeon may be able to directly
dissect across the mediastinum and decompress
the non-operative thorax, facilitating reinflation.
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One of the most serious complications of lung
transplantation occurs late. Bronchiolitis obliterans is a
syndrome characterized by alloimmune injury leading to
obstruction of small airways with fibrous scar. Patients
with bronchiolitis obliterans present with cough,
progressive dyspnea, obstruction on flow spirometry, and
interstitial infiltrates on chest radiograph. Therapy for
this syndrome includes augmentation of
immunosuppression, cytolytic agents (which have been
used with varying degrees of success), or
retransplantation in refractory cases.
Other complications are rejection of grafts which can be
prevented by immunosuppressive therapy.
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