Lung Transplant

Dave Sweet
 CASE
 You are currently the fellow working at VGH
and as you come in Monday morning the
charge nurse tells you that there are several
transplants going on today including a lung
transplant and that we are holding a bed. You
have several resident working with you that
are very excited and they start firing questions
off….
 CASE
 What diseases are currently we doing lung
transplants for?
1) Alpha1-antitrypsin
2) CF
3) COPD
4) IPF (UIP and occ NSIP)
5) IPAH (including Eisenmengers)
6) Sarcoidosis
 CASE
 What are the general goals for determining
the appropriateness of a lung transplant in a
individual patient?
 General Principles
 Need to consider the natural history and
prognosis of primary disease and weigh
against projected survival post transplant.
 Ultimate goal=
 Obtain max mileage from native lung,
conferring a greater overall survival time with
new lung.
 Avoiding death on the waiting list.
 General Principles
 Consider quality of life while on waiting list
compared to quality of life with new lung.
 Traditionally, looked at the median 2-year
posttransplant survival rate and compared this
to projected survival with underlying
condition.
 When former=longer….patients are transplant
candidates.
 General Principles
 2 year survival rate is not arbitrary number.
Two reasons why used.
1) Average waiting time is around 2 yrs.

2) Based on disease the first month mortality

varies greatly.
…..but then the mortality decreases relatively
linearly. This will compensate for this.
 CASE
 Do the survival rates for different diseases
vary post transplant? What is the generally
quoted first month mortality?
 CASE

First month mortality quoted as 7% to 24%

 CASE
 Which diseases are thought to have the
greatest survival advantages? Which
diseases are questionable?
 Survival advantage?
 Use of time-dependent, nonproportional
hazard models, equity points, and crossover
points.
 Survival benefit demonstrated with:
1) CF
2) IPF
3) IPAH
Critical Care Aspects of Lung Transplantation. Journal of Intensive Care Med 19(2); 2004
 Survival advantage?
 However, also raised questions about any
survival benefit for px with
1) COPD

2) Eisenmener syndrome

But in addition to survival, quality of life also

needs to be taken into consideration.
ie) COPD px changes in quality-adjusted life-years
may be sufficient to justify transplantation.
Survival advantage?
 CASE
 What are the indications for lung
transplantation for these various diseases
based on the ATS 1998 consensus statement?
 Indications
 COPD
 FEV1< 25% (without reversibility)
 And/or PaCO2 >55 and/or elevated PAP with
progressive deterioration
 Preference to those px with:
- elevated PaCO2 with progressive deterioration
- require long term oxygen therapy.
Nathan et al. Lung Transplantation: Disease-Specific Considerations for referral. Chest 2005;127:1006-1016
 Indications
 Interesting……the level of subjective dyspnea
my be a better predictor of mortality than
FEV1.
 ie) grade IV dyspnea= stopping to take a
breath during 100 yrd walk.
- median survival of 3 yrs, which is comparable
to 3 yr posttransplant survival rate (61%)
 In contrast, FEV1<35% pred had a median
survival of 5 yrs.
 Indications
 Currently several other models being
investigated which incorporate a number of
diff parameters such as the BODE index.
 Body weight, Obstruction, Dyspnea level,
Exercise tolerance.
 Score out of 10.
 7-10=80% mort at 52 months (transplant cand)
 <7= 5 yr mort of <50% (not transplant cand)
 Indications
 IPF:
 Divided now into UIP and NSIP
 UIP=When diagnosed should be referred!!!
 Traditionally, break points at FVC of 60-70%
and DLCO of 50-60% are indicative for poor
outcome. Very inconsistent.
 Indications
 Other models look at DLCO and HRCT scan
to help predict mortality (May see in future!)
 Also, one of the most sensitive markers may
be desaturation to less than 89% during a 6
min walk.
 If able to maintain sats may be able to defer
transplant referral.
 Indications
 NSIP:
 True NSIP have much better prognosis and
majority will not need transplant.
 Subgroup which may require include:

1) DLCO <35% and/or a dec in DLCO of >15%

have shown to have mortality similar to UIP
with median survival of 2 yrs.
 Indications
 CF:
 FEV1 <30% or
 Rapid progressive resp deterioration with
FEV1 >30% (inc hosp, rapid fall in FEV1,
massive hemoptysis, inc cachexia)
 Room air PaCO2 >50 or PaO2 <55.
 Woman whose condition is deteriorating
rapidly.
 Indications
 IPAH:
 Medical management has improved greatly.
 1990= 10.5% of all lung transplants.
 2001=3.6% of all lung transplants.
 Should exhaust all medical management
before consider transplant.
 Indications
 NYHA class III or IV after 3 months of IV
epoprostenol have 2 yr survival of 46% and
should be considered for transplant.
 NYHA class I and II= 93% and not candidate.
 Indications
 Sarcoidosis (common disease, rare transplant)
 In 1998 guideline no official recommendation.
 Need to have stage IV. Advanced fibrotic
changes, honey-combing, hilar retraction,
bullae, cysts, and emphysema.
 Also reasonable when FVC<50% and/or FEV1
<40%.
 CASE
 After you clearly describe the answers to the
above questions your staff speaks up and
asks you if you are familiar with the Lung
Allocation Score (LAS).
 What is the LAS? Why was it designed?
 LAS
 In Canada we determine how organs or
allocated by:
 Size of patient
 ABO matching (Not HLA matching)
 Time on the list.

Kozower et al. The impact of the lung allocation score on short-term transplant outcomes: A multicenter study. J thorac Cardiovasc
Surg 2008;135:166-77
 LAS
In the US:
 Organ procurement and transplantation network
(OPTN) began allocating lungs in 1990 based on size,
blood type and amount of time candidate had spent on
waiting list.
 1995, minor change when 3 months credit given to IPF
px to offset their inc mortality. (Not done in Canada)
 To better list px according to medical urgency and
expected benefit the LAS was developed.
 LAS
 Developed by multivariate modeling and
approved by OPTN in 2004. Implemented in
May 2005.
 Three main objectives are:
1) Reduce deaths on transplant list
2) Inc transplant benefit for lung recipients
3) Ensure efficient and equitable allocation of
organs
 LAS
 Gives a score between 1-100.
 Weighted combination of predicted risk of
death during the following year on the waiting
list and the predicted likelyhood of survival
during the first year after transplant.
 CASE
 Is there any evidence that it is working?
 First year of implementation compared to previous
year.
 170 in each group.
 Dec in waiting times (680 to 445 days).
 Dec death on waiting list (74 to 51…30%)
 Determined that there was a switch with inc in IPF px
and dec in COPD and CF.
 Inc in primary graft dysfunction (14.1 to 22.9%).
 Inc in ICU stay (5.7 to 7.8 days).
 Hosp mort and 1 yr survival were similar.
 Concluded that the LAS is doing what it was
designed to do.
 Reason why inc in PGD is likely due to higher
number of retransplants and IPF which both are
established risk factors for PGD.
 When controlled for Dx, the rates of PGD were no
longer different.
 This also explains the inc in ICU stay, mech vent.
 Most important…..no change in mortality.
Donor criteria?
Less than 20% of organ donors
possess lungs suitable for
transplantation
 Age <40 years (heart-lung), <50 years (lung)
 Smoking history less than 20 pack-years
 Arterial partial oxygen pressure of 140 mm Hg
on a fraction of inspired oxygen (FIO2) of
40% or 300 mm Hg on an FIO2 of 100%
 Normal chest x-ray Sputum free of bacteria,
fungi, 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
 Human immunodeficiency virus negative
 CASE
 You learn that the patient is a 58 yo male with severe
COPD. Other PMHx includes a NSTEMI 8 yrs prev,
HTN, hypercholesterolemia. Pre-op ECHO results
show good biventricular fxn with PAS=33 mmHg via
TRJ. Pre-op cath results show clean coronaries and
right heart cath confirms the right sided pressures.
Preop PFT show a PEV1 of 25% and moderate to
severe airtrapping. They are doing a single right lung
transplant and no plan for bypass.
 CASE
 8) How is the choice for a single vs a double
lung transplant made? In what situations is a
double lung preferred?
 Single vs Double?
 Based on numerous factors such as:
 Disease
 Age
 Comorbidities
 Institutional biases
 Organ availability
 Emergency of procedure
 Single vs Double?
 Majority done in Canada are single lung
transplants.
 First isolated single lungs were done for
pulmonary fibrosis and this continues to be the
norm.
 COPD originally thought not possible to
receive single lung transplants.
 First done in 1989 by Mal and colleagues
Critical Care Aspects of Lung Transplantation. Journal of Intensive Care Med 19(2); 2004
 Single vs Double?
 Currently a standard throughout the country.
 Specifically, in COPD if px is of shorter stature and
older do better.
 Pulmonary HTN= single or double but if choose
single expect to have more difficulty in first few days.
Many centers mandate only bilateral.
 Bilateral transplants are mandatory for px with CF
and bronchiectasis.

Critical Care Aspects of Lung Transplantation. Journal of Intensive Care Med 19(2); 2004
 Single vs Double?
 Bilateral lung transplants for mycetomas or
other chronic fungal or mycobacterial
infections
 Many larger centers are now favoring
bilateral transplants. Specifically the Duke
University Medical Center.

Critical Care Aspects of Lung Transplantation. Journal of Intensive Care Med 19(2); 2004
 Single vs Double?
1) Feel do not exclude other patient in many
cases.
2) If single lung is “marginal” for transplant,
taking both will provide adequate function.
3) Early post-op management is easier with
bilateral
 Single vs Double?
 Additionally, in 225 px who survive 6 months.
 Single lung transplant (as compared to
bilateral) was a significant risk for BOS in
multivariate Cox model (HR=2.08, p=0.001)
 ? If immunologic advantages of bilateral ?

Hadjiliadis D et. al. Chest 2002;122:1168-1175.

 Single vs Double?
 A recent review of the United Network of Organ
Sharing lung transplant database of 2260 transplants
for emphysema compared single vs double lung
transplants.
 No difference in 30 day mortality but long term
survival data favored bilateral lung transplants for
individuals <60 yrs of age.
 Bilat were older and more women. ? How to interpret?
Meyer et al. J heart Lung Transplant 2001;20:935-941.
 Case
 9) In what situations will a lung transplant be
done on bypass? Why if done on bypass is it
relevant to post-op management?
 Bypass?
 Most adult transplants can be done without CPB. A
number of specific situations will necessitate CPB.
1) Primary or secondary pulmonary htn are most safely
done on bypass.
2) Px with CF likely have such voluminous purulent
secretions that independent ventilation is
impossible.
3) During bilateral transplant early graft dysfxn of the
first transplanted lung (reperfusion) preventing
single lung vent.
4) If native lung is unable to sustain patient with single
lung ventilation.
 Bypass?
 Why relevant to post-op care?
1) If get significant PGD it is unlikely the patient can be
supported on single lung ventilation.
2) Bypass is a significant risk factor for PGD!!

Most recent large study by Dalibon, which reviewed

140 LT, confirmed that CPB was associated with
longer MV, more pulm edema, more transfusions and
inc early mortality!!
Dalibon et. al. J Cardiothorac Vasc Anesth 2006;20:668-672.
 CASE
 You hear that the case is finishing up. There
was minimal surgical difficulty the lung was
implanted using continuous 3/0 polypropylene
sutures for the bronchial anastomosis (end-
end-technique), continuous 4/0 polypropylene
sutures for the pulmonary vein to left atrial
anastomosis, and continuous 5/0
polypropylene sutures for the pulmonary
arterial anastomosis.
 CASE
 Unfortunately you hear that they need to do the
case on bypass as they were unable to do the
transplant on single lung ventilation. The overall
ischemia time was 6 hours and 8 minutes for the
lung. The post-transplant bronch looked
pristine and the TEE looked good. The patient is
brought to ICU post-op stable on AC and FIO2
of 100% and quickly weaned to 80%. CVP=12
CI=3.5, PA=40/18. (If the nurse said the
PAWP=16…what would you say??)
 CASE
 10) Generally what ventilator settings would
you like post transplant px to be on? What
about this patient? What is your general plan
to wean the ventilator?
 Ventilation?
 Many centers prefer a PC ventilation so as to
limit peak airway pressures (<40) and prevent
barotrauma to the brochial anastomosis.
 Plat pressure should additionally be limited to
less than 30 to 35 mmHg.
 Minimize Fio2 as quickly as possible.

Critical Care Aspects of Lung Transplantation. Journal of Intensive Care Med 19(2); 2004
 Ventilation?
 This patient?
 Due to the very compliant native lung with potential
for air trapping and the relatively stiff transplant
lung….need to be aware of balance.
 To begin, as long as oxygenation is not a issue.
Ventilation as if to prevent air trapping in native lung.
 Min PEEP, adequate expiratory phase with PC. Can
still use EEP to determine if airtrapping.
Critical Care Aspects of Lung Transplantation. Journal of Intensive Care Med 19(2); 2004
 Ventilation?
 Generally want to get off the ventilator as soon as
possible.
 Use adequate analgesia via epidural or paravertebral
(recent metaanalysis and found paravertebral block
had lower rate of resp complications and side effects)
….wake and wean.
 If have standard PS weaning protocol it should be
used as usual.
 Plan to have extubated in 24 to 48 hrs ideally!
Davies et. al. Br J Anaesth 2006; 96:418-426.
 CASE
 11) Generally discuss your fluid management
post op. What variables are you balancing
with your fluid management?
 Fluid Management
 Careful fluid management is necessary to avoid
substantial transplant lung edema.
 Usually aim for a negative fluid balance from the get
go. Def aim for negative balance in the first 48hrs.
 Minimal fluid and if require volume use colloid or
blood.
 Some centers will target a CVP of <7 mmH20, with
systemic perfusion supported by pressors.
Pilcher et. al. A high CVP is associated with prolonged mech vent and inc mortality following lung
transplantation. J Thoracic Cardiovasc Surg 2005;129:912-918.
 Fluid Management
 Retrospective study of 118 px.
 After controlling for CV diz and vasopressors,
CVP was correlated with duration of MV, with
a CVP >7 also being associated with higher
ICU and hosp mortality.
 Unclear whether a strategy aimed at keeping
CVP less than 7 would alter outcome or if a
marker of severity of illness.
Pilcher et. al. A high CVP is associated with prolonged mech vent and inc mortality following
lung transplantation. J Thoracic Cardiovasc Surg 2005;129:912-918.
 Fluid Management
 Obviously need to balance against the risk of
renal insufficiency.
 Many of these patient my have
CRF….specifically the CF px. (why?).
 Additionally cyclosporine or tacrolimus may
impair renal fxn. Watch levels closely post-op.
 Titrate volume to u/o. Previous many centers
still using “renal dose dopamine” in this setting.
No evidence.
 CASE
 12)Although our patient remains
hemodynamically stable. Why is shock in
these patients need to be quickly identified and
diagnosed?
 CASE
 These patients should not be shocky!!
 “NEED TO MAKE DIAGNOSIS”
(Dr George Isac)
 Bleeding? Anastamosis?(watch CTs and hgb)
 Obstructive? Anastamosis?
 Cardiogenic?
 Infection/sepsis?
 CASE
 Judicious resuscitation (colloid) and
vasopressors
 STAT ECHO (TEE)
 Notify the Surgeon
 ? Mobilize ECMO early?
 Is their a benign reason why they may be
requiring increasing vasopressor support?
 CASE
 After initially settling the patient in and
continuing on your rounds the RT approaches
you and states that the FIO2 requirements are
back up to 100% after a brief period at 50%
and hypoxia is becoming an issue. A stat CXR
was done.
CASE
 CASE
 13) What is your differential for early
respiratory failure in the lung transplant?
What are the risk factors for early respiratory
failure?
 Early Respiratory Failure
 DDx:
1) Reperfusion injury (55%)
2) Periop cardiovascular(MI, arrhythmia, CHF)
/haemorrhagic (36%)
3) Anatomic complications
4) Infectious (bacterial and CMV)
5) Rejection (hyperacute=rare and acute=common)
6) Pneumothorax
7) PE
Chatila el. al. Resp failure after lung transplant. Chest 2003;123:165-173.
 Early Respiratory Failure
 Risk factors:
1) Preop pulmonary htn
2) Rt vent dysfunction
3) Prolonged ischemic time
4) CPB

Chatila el. al. Resp failure after lung transplant. Chest 2003;123:165-173.
 CASE
 14) Briefly describe Reperfusion injury,
Primary Graft failure. What can we do to help
prevent Reperfusion injury before and after the
transplant? How do you manage it?
(specifically in our patient?)
 Ischemia-Reperfusion Injury
 Typically manifests in the first 72 h after
transplant.
 Development of airspace disease, progressive
hypoxemia, and inc in pulmonary pressures
(reflective both epithelial and endothelia injury)
 When PaO2/FiO2 ratio below 200, termed
primary graft failure.

Granton, J. Update of early resp failure in the transplant recipient. Current Opinion in Critical Care 2006;12:19-24.
 Ischemia-Reperfusion Injury
 Recent 2004 publication identified several risk
factors:
 CPB
 BMI >25kg/m2
 Immediate elevated PAS
 Trend in oxygenation index over 24hrs
 Elevated APACHE II
Sekine et al. J Heart Lung Transplant 2004;23:96-104
 Ischemia-Reperfusion Injury
 Additionally, a review of 7 French transplant centers
and 752 px over 12 yrs.
 Found graft ischemic time associated with the
PaO2/FiO2 ration measured at 6 hrs.
 30 day mortality was associated with a lower
PaO2/FiO2 ratio at 6 hrs.
 Identified cold ischemic time of 330 min (5.5hr) as
distinguishing between px who had a uncomplicated
course vs those who did not. (Max accepted is 6-8hrs)
Thabu et al. Am J Respir Crit Care Med 2005;171:786-791.
Oto et al. J Thorac Cardiovasc Surg 2005;130:180-186.
 Ischemia-Reperfusion Injury
 Ischemia-Reperfusion Injury also associated with
long-term consequences.
 Retrospective cohort study of 255 LT px.
 Christie et al reported a 30 day mort of 63.3%
compared to 8.8% in px with and without reperfusion
injury.
 Median hosp was longer (47 vs 15 days)
 Mech vent longer (15 vs 1 day)
 Lower exercise capacity as assessed by 6 min walk
distance at 12 months.
Christie et al. Chest 2005;127:161-165.
 Ischemia-Reperfusion Injury
 Pathogenesis:
 Variety of perturbations implicated.
 Factors relating to:
1) Donor
2) Method of graft preservation
3) Effects of reperfusion following period of
ischemia
 Ischemia-Reperfusion Injury
 The Lungs may be made susceptible from cytokine-
mediated damage in px with elevated ICP and
compounded following cold preservation of the grafts.

De Perrot et al. Am J Respir Crit Care Med 2003;167:490-511

 Ischemia-Reperfusion Injury
 How can we help prevent ischemia-
reperfusion injury?
 Can divide into:
1) Pre-transplant interventions
2) Peri-surgical interventions
3) Post-surgical interventions
Ischemia-Reperfusion Injury
 Ischemia-Reperfusion Injury
 Pre-Surgical interventions:
 Preservation solution…specifically a low-
potassium dextran solution provides superior
preservation over high potassium preservation
solutions.
 In addition, nitric oxide added to the flush
during harvest provides a preservation
advantage. (not well studied)
Maccherini et al. Transplantation. 1991;52:621-626
Yamashita et al. Ann thorac Surg. 1996;62:791-797
 Ischemia-Reperfusion Injury
 It is known that lung hyperinflation is a
excellent model of pulmonary
edema….therefore care should be taken to
avoid during harvest and storage.
 Ischemia-Reperfusion Injury
 Peri-Surgical interventions:
 Lick and colleagues reported a small series
where using leukocyte-filtered modified
perfusate is pumped through the lung at time
of reperfusion. In case report….no ischemia-
reperfusion injury.

Lick et al. Ann Thorac Surg. 2000;69:910-919

 Ischemia-Reperfusion Injury
 Post-surgical interventions:
 TP-10 inhibitor

- One of few randomized trials in lung

transplantation, using soluble complement
receptor-1 inhibitor led to reduction in
duration of mech vent.
- Interestingly, greatest effect in px who received
bypass.
 Ischemia-Reperfusion Injury
 NO
- Early preclinical and uncontrolled reports
suggested that admin of NO either prior to or
shortly after reperfusion injury could dec
severity of disease.
- Recent controlled clinical trial failed to show
benefit when inhaled 10 min after reperfusion.
Meade et al. Am J Respir Crit Care Med 2003;167:1483-1489.
 Ischemia-Reperfusion Injury
 NO
- Another recent trial by Perrin.
- RCT in 30 bilateral lung transplants.
- 20 ppm iNO at time of reperfusion vs control.
- Could not identify any reduction in
extravasular lung water (p=0.61) or
improvement in gas exchange (p=0.61).
- Future studies needed.
Perrin et al. Chest 2006;129:1024-1030
 Ischemia-Reperfusion Injury
 ICU management:
 Adoption of lung protective strategy would
seem reasonable. (only one rat study has
actually looked at this).
 “In refractory hypoxemia use of inhaled NO,
HFO and ECMO may improve gas exchange.”

Granton, J. Update of early resp failure in the transplant recipient. Current Opinion in Critical Care
2006;12:19-24.
 Ischemia-Reperfusion Injury
 What about our patient??
 In COPD single lung Tx that develop reperfusion
injury….dilemmas may arise.
 As px becomes hypoxic and more aggressive
vent/peep strategies are used….may overdistend
native lung.
 Cause shunting of blood to dysfunctional allograft.
 Futhermore, if worsens still, mediastinal shift may
result in impaired venous return.
 Ischemia-Reperfusion Injury
 Better to minimize tidal volumes and lowest PEEP to
gain acceptable oxygenation and accepting mild
respiratory acidosis (+/- novalung??)
 Place px in lateral decubitus with transplant side up,
and aggressive chest physiotherapy.
 If this fails….should consider independent lung
ventilation.
 Be aware that will be more difficult to clear secretions
and the ease with which the tube may be dislodged.
Gavazzeni et al. Chest. 1993;103:297-299.
 Prediction of Independent Lung
Vent.
 Prediction of need for single lung ventilation?
 Study looking at 170 px who had single lung
transplant for COPD.
 12% required independent lung ventilation.
 Similar in age, sex, ischemic time, and donor
characteristics to those who required
conventional ventilation.

Pilcher et al. Predictors of independent lung ventilation: an analysis of 170 single-lung transplantations. Pilcher J Thorac Cardiovasc
Surg. 2007 Apr;133(4):1071-7
 Prediction of Independent Lung
Vent.
 Patients receiving independent lung ventilation
had a greater degree of:
 Preoperative airflow limitation (FVC1/FVC)
 More hyperinflation
 Lower postoperative PaO2/fraction of inspired
oxygen ratios
 More radiologic mediastinal shift
 More transplant lung infiltrate on the
postoperative chest radiograph.
 Prediction of Independent Lung
Vent.
 Multivariate logistic regression analysis showed
that independent lung ventilation was
associated with:
 Increasing levels of recipient hyperinflation
(percentage total lung capacity compared with
predicted value; odds ratio 1.04;P = .032)
 Reduced early postoperative PaO2/fraction of
inspired oxygen ratio (odds ratio 0.96; P = .005)
 Prediction of Independent Lung
Vent.
 Length of ventilation and intensive care unit
stay and mortality were higher in the
independent lung ventilation group.
 Among patients who survived to hospital
discharge, there were no differences in long-
term mortality between the 2 groups.
 Prediction of Independent Lung
Vent.
 Conclusions= Independent lung ventilation
predicted by the combination of:
 Increased hyperinflation measured on
recipients' preoperative lung function tests
 Low PaO2/fraction of inspired oxygen ratio,
indicating graft dysfunction in the immediate
postoperative period.
 Prediction of Independent Lung
Vent.
 Another study looking at predictors of native lung
hyperinflation.
 Retrospectively analyzed data from 27 patients who
underwent 31 single lung transplantations for
emphysema.
 Two groups:
- 12 patients with development of acute or chronic
NLH
- 15 patients without development of hyperinflation
Yonan. Single lung transplantation for emphysema: predictors for native lung hyperinflation. J Heart Lung Transplant. 1998 Feb;17(2):192-201
 Prediction of Independent Lung
Vent.
 NLH was defined as:
 Radiologic mediastinal shift with
 Flattening of the ipsilateral diaphragm
 Associated with respiratory dysfunction or
hemodynamic instability
 Prediction of Independent Lung
Vent.
 No differences between the two groups regarding:
 age
 preoperative partial pressure of oxygen
 partial pressure of carbon dioxide
 acid-base status
 donor lung size and physiological structure
 side of transplantation
 primary pathologic condition
 rejection score
 infection episodes and obliterative bronchiolitis in the
transplanted lung after operation.
 Prediction of Independent Lung
Vent.
 Patients with NLH had:
 Significantly higher preoperative mean
pulmonary artery pressure > 30 mm Hg.
 Lower mean FEV1.
 Higher mean residual volume.
 CASE
 A quick in and out bronch shows no anatomic abn
and on TEE the pulmonary veins look good. After a
short period of time you realize that he is
deteriorating that the hypoxia is quickly becoming
refractory. You quickly mobilize ECMO and after
a short time on ECMO the patient stabilizes.
15) Your staff asks you if you know of any evidence for
the use of early ECMO in these patients?
 ECMO
 Several publications looking
at ECMO in this situation.
 In the setting of pulmonary
htn (high risk), early ECMO
has been advocated
(experience based).
 Another review of 17 cases
 ECMO may preserve initial
organ function due to
reduction in use of injurious
ventilation strategies.
Dahlberg et al. J Heart Lung Transplant 2004;23:979-984.
Pereszlenyi et al. Eur J Cardiothorac Surg 2002;21:858-863.
 ECMO
 More recent publication by Oto at Alfred Hosp
in Melbourne.
 Ten transplant recipients from total of 481
(2.1%) were treated with ECMO.
 Prior to initiation had TEE to exclude lung
torsion and pulmonary vasc prob, and a
retrospective crossmatch to exclude humoral
rejection.
 ECMO
Initiate 21 days (7- Initiated after 0-2 days
40days)
ECMO
 CASE
 One of your keen residents asks if there is
anyway this could be acute rejection? Are
there any definitive tests to prove this is not
rejection?
 Biopsy!!
 Patients with acute rejection can also have alveolar
infiltrates, hypoxemia and systemic inflammatory
response syndrome.
 To rule out hyperacute rejection can do a
retrospective crossmatch.
 For longer term observation pathologic assessment of
multiple transbronchial biopsy specimens has proven
to be the gold standard.
 Debate between transbronchial and surgical biopsy.
Trulock et al. Chest. 1992;102:1049-1054.
 Open Lung Biopsy
 In 2003 Burns et al looked at 41 patients on mech
vent with questionable acute rejection that received
transbronchial and open lung biopsy.
 Surgical biopsy inc dx of rejection by 33% and
treatment changes in 15 of the 41.
 Currently unresolved debate as previous studies
contradicted this finding.

Burns et al. J Heart Lung Transplant 2003;22:267-275.

 Open Lung Biopsy
 The risk of open lung biopsy must be weighed
against the risk of simple empirical therapy for
rejection after exclusion of infection.
 Given the consequences of intensification of
immunosuppression in the intubated, critically
ill px, open lung biopsy may be justifiable.
 CASE
 Now that the possibility of rejection has been
brought up…..what are the different types of
rejection? How are they treated?
 Rejection
 Hyperacute- humoral based with preformed
antibodies to the allograft vascular endothelium
- Only anecdotally reported in the literature with
lung transplant.
Cellular immune based rejections
 Acute

 Chronic/bronchiolitis obliterans syndrome

(BOS)
 Rejection
 Standard immunosuppressive management:
 Triple drug combo=cyclosporin, imuran, prednisone.
 Methylprednisolone intraop and first 24 hrs. Then
steroids suspended for 2 weeks, based on
experimental and clinical evidence they impede
bronchial anastamotic healing.
 Then oral pred started.
 Some evidence tacrolimus/imuran/steroid may be a
better combo. (acute and chronic rejection)
 Rejection
 Acute:
 Most common complication following lung
transplantation.
 Most recipients experience at least 1 episode
in first year.
 It is clear that there is a association between
frequency and severity of acute rejection and
subsequent dev of BOS.
 Rejection
 Thus, early detection and alteration of
immunosuppression may have a significant impact on
subsequent reduction of BOS.
 S/S:
 Fever
 Dyspnea
 Dec PaO2
 Fall in vital capacity
 Infiltrates.
 Rejection
 After first postop month, CXR freq normal
during episode of acute rejection.
 Obviously, infection can present similarly.
 Need to distinguish with transbronch biopsy
and BAL.
 Tx:
 Methylprednisolone 10-15mg/kg for 3-5 days.
 2-3 weeks of oral steroid taper.
 Rejection
Some work by Loubeyre et al, that may be able to use HDCT to
Dx acute rejection and avoid TBB (65% sens for rejection, 85%
specific for acute lung complication.
 Rejection
 Maintenance immunosuppression regimen
should also be scrutinized.
 First adjustment from maintenance cyclosporine
is a switch to tacrolimus in event of cyclosporin
toxicity or acute rejection episodes despite
adequate cyclosporine dosage.
 Newer agents such as sirolimus, leflunomide
may be used more in future.
 Rejection
 Chronic/bronchiolitis obliterans syndrome(BOS):
 70% of graft recipients are dx by 5th year.
 Usually presents as a late decline in FEV1 from a
post-op baseline.
 Pathologic lesion is broncholitis obliterans.
 Rejection
 Risk Factors:
 Episodes of acute rejection
 Primary Graft dysfunction
 CMV pneumonia
 Noncompliance with meds
 Rejection
 Causes not totally clear.
 Evidence suggests both alloimmune and non-
alloimmune mech are important (for example
GERD).
 There is evidence that fundoplication will
lower BOS scores and even eliminate it in
certain individuals
Cantu et al. Ann THorac Surg 2004;78:1142-51
 Rejection
 Diagnosis- two approaches (definitive proof and
diagnosis of exclusion)
 Rejection
 Treatment: (no well established protocol)
 Conversion from cyclosporin to tacrolimus
may stabilize progression.
 ?addition of mycophenolate may be benificial.
 ?sirolimus
 ?azithromycin daily is currently being
investigated and may show promise.
 Retransplantation?
 CASE
 17)Could this be infectious? Where in the
complications timeline to infectious etiologies
usually fit? Are there any exceptions?
 Infection post transplant
 Unlikely in this scenario.
 But infection is one of the leading causes of
morbidity and mortality.
 Immediate post-op bacterial are the greatest
threat.
 But candidia or aspergillus or viral (herpies or
CMV) can also arise.
Lung transplant: procedure and postoperateive management. 2008 Uptodate.com.
 Bacterial
 Most common pathogen are those that colonized the
donor or recipient.
 Gram neg such as Pseudomonas, Klebsiella and H.
flu are most common. Gram positives (staph) are also
a frequent cause (head injury).
 Most centers use a 7-10 day prophylaxis (eg vanco,
cefepime) or depending on previous colonization.
 We use generally use ceftaz and clox till lines and
drains are out.
 Viral
 CMV is most commonly seen infection post-op
complication (13-75% of transplants).
 Most risk obviously in CMV neg recipient receiving
CMV pos donor.
 Optimal prophylaxis remains controversial.
 Most centers will supply 12 weeks of IV gancyclovir
(5 mg/kg qd) for +D/-R and CMV immunoglobulin.
 If just +R get only gancyclovir for 12 weeks.
 If –D/-R nothing.
 Viral
 Patients in the community are also susceptible
to other viral infections (eg. RSV, adenovirus,
influenza, parainfluenza).
 Several of these have specific treatments so be
aware of them (eg. Aerosolized ribavirin)
 Fungal infections
 Major problem in the long term.
 Aspergillus and Candida account for majority.
 Both can represent colonization but also can
be life-threatening infections.
 Aspergillus colonization and infection occur
within first 6 months.
 Mortality for pneumonia/disseminated disease
approaches 60%.
Critical Care Aspects of Lung Transplantation. Journal of Intensive Care Med 19(2); 2004
 Fungal infections
 Several antifungal prophylactic strategies used.
 Systemic or inhaled or both.
 However, use of systemic antifungal therapies
limited by lack of in vitro activity against some
infections, drug interactions, significant
treatment limiting toxicities.
 Several reports of using inhaled Ampho B lipid
complex….may see used in future.
 Fungal infections
 What do we do?
 Candida prophylaxis= nystatin swish and
swallow.
 PCP= septra or aerosolized pentamidine.
 Aspergillus=aerosolized ampho B.
 Toxoplasma neg px= pyrimethamine for 6
months.
 Fungal infections
 Although bronchial dehiscence is a rare complication
due to improved surgical tech and lack of steroids for
period of time after OR.
 B/c of inherent ischemia occurring at the anastomosis
fungal infections my develop at this site.
 This can lead to life threatening airway
complicatoins.
 Careful attention should be paid to this area on all
bronchoscopies.
 Fungal infections
 In one study by Nunley it was found that 46.7% with
anastamosis infections had airway complications
where in only 8.7% of patients without.
 These included bronchial stenosis, bronchomalacia,
fatal hemorrhage and dehiscence.

Nunley et al. Chest 2002;122:1185-1191.

 Fungal infections
 If on bronchoscopic inspection have
pseudomembranes should perform biopsy.
 Optimal treatment still unknown.
 Suggested expert opinion is that should use
combination of systemic and inhaled
antifungal agents. (eg. Ampho B)
 May need bronchoscopic debridement of the
tissue.
 Fungal infections
 Treatment of systemic infections.
 Albicans still fluconazol.
 Non-albicans caspofungin.
 Ampho B is classic drug of choice for
aspergillus and fusarium. More utilization of
Vori and caspo in last several years.
 Careful with Vori as has extensive interactions
with immunosuppressants.
Nunley et al. Chest 2002;122:1185-1191.
 CASE
 The oxygen delivered via ECMO was adjusted
according to the arterial blood gas results, and
was successfully reduced to 40% within 4
days. After the first 48 hours, the ECMO flow
rate was maintained at 2.5 L/min, with 3200
RPM. Prior to discontinuation of ECMO, the
patient was relying on his lung for
oxygenation with no oxygen given through the
oxygenator.
 CASE
 Both the cannulae were successfully removed with
application of pressure on the site and without any
problems. The patient did very well there after and
was discharged to the ward within 8 days.
 While on the ward several surveillance
bronchoscopies were performed. There were some
pseudomembrains seen near the anastomosis and they
were sampled. They were positive for candida sp.
and treatment initiated with IV caspofungin. The site
looked stable during repeated bronchoscopy.
 CASE
 On day 15 you are called to the ward for
respiratory decline. He is in respiratory
distress and a CXR is performed.
 CASE
 What is high on your differential for the cause
of the abnormality?
 The patient requires reintubation, independent
lung ventilation and is taken to the OR for
repair of his bronchial dehiscence.
 Is there any evidence for the outcomes of Lung
transplant patients who require readmission to
the ICU?
 All lung transplants at Duke University Medical Center
discharged from hosp between March 99 and Feb 01.
 51/214 px (23.8%) required ICU admissions.
 Of those 27/51 (57.5%) required MV.
 Dx:
 Resp failure (70%)
 Sepsis (6.8%)
 Pneumothorax, atrial fib, high-risk bronchoscopy, PE,
antibiotic desensitization and cardiac arrest (2.7% each)
 19/51 (37%) died during their ICU admission.
 16/27 (59%) receiving MV died.
 Px who died had lower FEV1 to posttransplant
best FEV1 ratio prior to ICU admission. (51%
vs 75% p=0.001)
 Also, had higher APACHE III scores on ICU
admission compared to survivors.
 Survival rates by Kaplan-Meier:
 1 year= 43.1%
 2 year= 40.9%
 Conclusions:
 ICU admission and mechanical ventilation, is
associated with a poor prognosis in lung
transplant but….
 Is appropriate for selected patients with good
allograft function.
 Conclusions
 More immediate ICU complications with IPAH and
IPF.
 Beware the patient that required by-pass or that did
poorly on single lung ventilation.
 If become shocky….act quickly and look for the
diagnosis. (? Bleeding, STAT TEE, contact surgeon)
 Reperfusion injury is a diagnosis of exclusion and
may require independent lung ventilation or ECMO.
 Conclusions
 Predictors of need for independent lung ventilation
include preoperative airflow limitation (FVC1/FVC)
and hyperinflation.
 Mobilize ECMO early.
 If questioning diagnosis of acute rejection vs
infection use open lung biopsy.
 Acute rejection is a marker for future BOS….we may
be able to make a difference.
 Patients with post-op good allograft function should
be candidates for readmission to ICU.