Critical Care Management of The Lung Transplant Recipient

C r i t i c a l C a re M a n a g e m e n t
o f t h e Lu n g Tr a n s p l a n t
Recipient
Jake G. Natalini, MD, MSCEa,*, Emily S. Clausen, MDb
KEYWORDS
Critical care Lung transplantation Primary graft dysfunction Acute rejection
Extracorporeal membrane oxygenation
KEY POINTS
Extracorporeal membrane oxygenation can be successfully used as a supportive means to bridge
critically ill patients to lung transplantation, either without or in conjunction with mechanical
ventilation.
Graft failure (including primary graft dysfunction and acute rejection) and non-cytomegalovirus
infection are the most common causes of mortality in the first year after lung transplantation,
whereas bronchiolitis obliterans syndrome, a subtype of chronic lung allograft dysfunction, is the
most common cause of death among lung transplant recipients who survive beyond 1 year.
Primary graft dysfunction is a form of acute allograft ischemia-reperfusion injury characterized by
hypoxemia and radiographic alveolar infiltrates that develop within 72 h after lung transplantation.
Anastomotic complications such as ischemia and necrosis, bronchial dehiscence, bronchial infec-
tions, and bronchial stenosis are common in the first few weeks to months after lung transplanta-
tion, in part because of a lack of revascularization of the bronchial circulation.
The three types of allograft rejection, categorized according to the timing of onset after lung trans-
plantation and distinct histopathologic features, are antibody-mediated rejection, which can rarely
appear as a form of hyperacute rejection, acute cellular rejection, and chronic lung allograft
dysfunction, which can present as bronchiolitis obliterans syndrome and/or restrictive allograft syn-
drome.
INTRODUCTION such as primary graft dysfunction (PGD), acute

rejection, and infections.2 However, lung trans-
Lung transplantation has become an increasingly plant recipients still experience frequent complica-
utilized therapeutic intervention for patients with tions, often requiring treatment in an intensive care
end-stage lung diseases.1 Since the first success- environment. In addition, both invasive mechanical
ful lung transplant was performed in 1983, survival ventilatory support and extracorporeal life support
outcomes have steadily improved, likely because (ECLS) are being more frequently utilized as a
of a multitude of factors including better donor means of bridging critically ill patients to trans-
and recipient selection, systematic changes in or- plants.3 As such, lung transplant candidates and
gan allocation, surgical advancements, modifica- recipients have had an ever-growing presence in
tions to immunosuppression, and evolving surgical and medical intensive care units (ICUs)
practices in managing postoperative illnesses worldwide.
chestmed.theclinics.com
a
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New York University
Grossman School of Medicine, 530 First Avenue, HCC 4A, New York, NY 10016, USA; b Division of Pulmonary,
Allergy, and Critical Care, Department of Medicine, Perelman School of Medicine at the University of Pennsyl-
vania, Hospital of the University of Pennsylvania, 3400 Spruce Street, 9036 Gates Building, Philadelphia, PA
19104, USA
* Corresponding author.
E-mail address: jake.natalini@nyulangone.org
Clin Chest Med 44 (2023) 105–119

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106 Natalini & Clausen
Bridging to Lung Transplantation in an severe bronchiectasis, lower-flow platforms such

Intensive Care Setting as extracorporeal carbon dioxide removal
(ECCO2R) may have potential use.10,11 One case
In the spring of 2005, the lung donor allocation
report previously described successful bridging
system was revised to assign priority for lung of-
to redo lung transplantation with ECCO2R.12 How-
fers based on a need-based lung allocation score
ever, future studies comparing the use of ECCO2R
(LAS) rather than accumulated time on the waiting
and VV EMCO as bridging strategies for lung
list.4,5 The LAS aimed to prioritize sicker patients
transplantation are needed.
who were more likely to benefit from lung trans-
Regardless of a patient’s ECMO configuration,
plantation. Given the high LAS scores for critically
there is a growing body of evidence supporting
ill patients in the ICU and the more likely availability
safe ambulation and rehabilitation practices for
of suitable donors within weeks for these highest
patients on ECMO, including central VA ECMO
LAS patients, there has been an increase in the
platforms and VV and peripheral VA ECMO plat-
use of advanced modalities of support such as
forms with femoral cannulation(s).13–15 Although
invasive mechanical ventilation and extracorporeal
practices vary, one possible bridging strategy is
membrane oxygenation (ECMO) for actively listed
to preferentially utilize ECMO to support patients
patients awaiting transplant.3 One prior study
awaiting lung transplantation (in the absence of
noted a significant improvement in 1-year post-
ECMO-related complications) to minimize or fully
transplant survival among patients bridged to
eliminate the need for MV support. In doing so, pa-
transplant with ECMO from 25% in the early
tients generally require less sedation and can more
2000s to 74% only a decade later.6 Another United
easily engage in ongoing rehabilitation while await-
Network for Organ Sharing (UNOS) registry study
ing transplant.
reported increasing use of ECMO as a bridging
strategy to lung transplantation, with similar sur-
vival rates relative to those recipients who were Complications of Extracorporeal Membrane
bridged with mechanical ventilation (MV).7 Despite Oxygenation
these similarities, recent data suggest that pa-
Potential complications from ECMO are not incon-
tients who require bridging with either MV or
sequential and include bleeding, limb ischemia,
ECMO have worse outcomes in comparison to
infection, renal failure, and stroke, among others.
those patients who do not require any bridging.7
A retrospective study using the Extracorporeal
However, a 2018 single-center study found that
Life Support Organization (ELSO) registry showed
patients less than 40 years of age bridged to trans-
that up to 30% of patients on VA ECMO support
plant on ECMO had similar survival rates
have bleeding complications, which is a higher
compared to those recipients who did not require
overall incidence than VV ECMO, albeit serious
any bridging,8 suggesting that age may be an
gastrointestinal and pulmonary hemorrhage were
important factor in deciding whether a patient is
more common among VV ECMO subjects.16 Con-
a candidate for ECMO bridging to transplant if clin-
cerning stroke, another ELSO registry study in VV
ically necessary.
ECMO subjects showed an incidence of 2.8% for
Expertise in ECMO has increased significantly
intracranial hemorrhage and 1.2% for ischemic
since the CESAR trial, which studied the use of
stroke.17
early ECMO in the management of acute respira-
Acute kidney injury (AKI) is common among the
tory distress syndrome (ARDS).9 Determining an
critically ill population. A large, single-center retro-
appropriate ECMO strategy is based upon the
spective study of VA ECMO (not specific to lung
characterization of respiratory failure, degree of
transplantation) showed a significant survival
right ventricular dysfunction, need for circulatory
disadvantage for those subjects who required
support, and insertion sites (peripheral vs central).
renal replacement therapy (RRT) either before or
A venovenous (VV) ECMO configuration provides
after initiation of ECMO support.18 A recent
support for both severe hypercapnic and hypox-
meta-analysis examining the overall incidence of
emic respiratory failure, whereas venoarterial (VA)
AKI for those on ECMO support reported the
or hybrid configurations are utilized in the setting
need for RRT because of AKI in over 40% of pa-
of hemodynamic instability, often because of sig-
tients.19 The UNOS registry data also demon-
nificant pulmonary hypertension with right ventric-
strated a more than three-fold increased risk for
ular dysfunction in patients awaiting or undergoing
AKI requiring in-hospital dialysis for those trans-
evaluation for lung transplantation.
plant recipients bridged with ECMO compared to
Among individuals with isolated severe hyper-
those not requiring ECMO bridging.7
capnic respiratory failure, often seen in end-
As cardiac output improves, patients with a pe-
stage chronic obstructive pulmonary disease or
ripheral VA ECMO configuration must be
Critical Care in Lung Transplant 107
monitored for north-south (or Harlequin) syn- FiO2 over positive end-expiratory pressure
drome, in which poorly oxygenated blood carried (PEEP) (69% vs. 31%). The median minimum
through the pulmonary circulation and not through PEEP used was 5 cm H2O and the median
the ECMO circuit is ejected out of the left ventricle maximum was 11.5 cm H2O. Tidal volumes were
and flows anterograde thereby limiting the retro- frequently based on recipient and not donor char-
grade flow of oxygenated blood to the upper ex- acteristics, and most respondents selected 6 mL
tremities and brain.20 Although far more invasive, per kg of recipient IBW as a target. In the setting
a central VA ECMO configuration in which the of PGD, the plateau pressure limit for adjusting
outflow cannula is positioned in the ascending tidal volumes was 30 cm H2O—27likely an extrap-
aorta obviates this risk. Alternatively, a second olation from ARDS management guidelines.28
outflow cannula can be placed in the right internal Certain patient populations require special
jugular vein or a subclavian vein referred to as a ventilator management. For example, mechani-
VAV ECMO configuration.21,22 cally ventilated patients with obstructive airway
disease can develop auto-PEEP if they have
Intraoperative Mechanical Circulatory Support excessive minute ventilation that results in a rela-
tively short expiratory time.29 Among single-lung
Regardless of the need for advanced bridging
transplant recipients, auto-PEEP can lead to
strategies, ECMO support or, in some cases, car-
native lung dynamic hyperinflation, which in turn
diopulmonary bypass (CPB) is often required for
can compromise the newly transplanted lung and
patients with pulmonary hypertension but may
lead to hypotension and hemodynamic instability.
also be necessary for those who cannot tolerate
This problem is magnified among patients who
single-lung ventilation and perfusion because of
develop PGD or pneumonia in the newly trans-
hypoxemia or hemodynamic instability. There
planted allograft, thus, decreasing its compliance.
has been an increasing number of cases (nearly
In such cases, increased minute ventilation may
50% at some institutions) performed on ECMO
be required for more effective CO2 removal, along
or CPB.23 However, there are no randomized
with higher PEEP to promote improved oxygena-
controlled trials and only a limited number of
tion. Consequentially, the more compliant emphy-
cohort studies comparing clinical outcomes for
sematous lung becomes overexpanded and can
lung transplantation performed on ECMO versus
herniate toward the contralateral hemithorax.30 At-
CPB. Both intraoperative ECMO and CPB are
tempts to prevent or manage this possible compli-
associated with a higher risk of PGD in the imme-
cation by using selective independent ventilation
diate postoperative period.24,25 The use of ECMO
with a double-lumen endotracheal tube have
may carry less risk for bleeding complications,
been tried, although modern-day practices gener-
acute renal failure, and early mortality in compari-
ally favor the use of ECMO to address this compli-
son to CPB, although unplanned or prolonged
cation.31,32 Of note, lung hyperinflation is
CPB may be a more important risk factor for
associated with a significantly longer stay in the
increased morbidity and mortality than CPB it-
ICU, a longer duration of MV, and a trend toward
self.24 Finally, prolonged CPB time can be compli-
higher mortality.33 For this reason, among others,
cated by postoperative vasoplegia, often
a bilateral lung transplant is nowadays more
necessitating hemodynamic vasopressor
commonly recommended for patients with severe
support.26
emphysema.
Patients further out from lung transplantation
Postoperative Ventilatory Management
who develop chronic lung allograft dysfunction
After lung transplantation, patients are transitioned (CLAD), synonymous with chronic rejection, also
to a single-lumen endotracheal tube and trans- require special ventilatory considerations. CLAD
ferred to an ICU. Most patients are ventilated in encompasses two distinct subtypes: bronchiolitis
either a volume assist-control mode or a pressure obliterans syndrome (BOS), which is the obstruc-
assist-control mode. Low tidal volume ventilation tive and far more common phenotype; and restric-
strategies are preferred, ideally targeting volumes tive allograft syndrome (RAS), which is the
between 6 and 8 mL per kg of the donor’s ideal restrictive, less common phenotype.34 Strategies
body weight (IBW) rather than the recipient’s for mechanically ventilating a patient with BOS
IBW. In a recent international survey on MV prac- should be aimed at prolonging expiratory time
tices after lung transplantation, 35% of respon- and minimizing risk for dynamic hyperinflation,
dents preferentially used volume assist-control akin to ventilatory strategies in severe asthma ex-
ventilation, whereas 37% of respondents acerbations or end-stage chronic obstructive pul-
preferred pressure assist-control ventilation. In monary disease. Conversely, strategies for
addition, survey respondents favored limiting mechanically ventilating a patient with RAS should
prioritize utilizing lower tidal volumes and main- recipient or the donor CMV IgG serologies are
taining acceptable plateau pressures to avoid positive before surgery.38 Finally, most transplant
barotrauma. centers routinely administer prophylactic anti-
Among patients meeting commonly accepted fungal agents such as inhaled amphotericin B, vor-
weaning criteria, extubation can be performed as iconazole, posaconazole, or isavuconazonium
early as 12 to 24 h postoperatively in the absence postoperatively, although there is significant vari-
of any complications, preferably to a high-flow ability across transplant centers about specific
nasal cannula to minimize risk for reintubation.35 antifungal regimens and their respective
durations.39
Post-surgical pain management strategies vary
General Postoperative Management
by transplant center and typically require a multi-
In cases of prolonged allograft ischemic times modal approach. Pain is often managed with opi-
where PGD is likely to develop or if the donor oids such as intravenous fentanyl, morphine
lung is oversized, a surgeon may elect to delay sulfate, or hydromorphone and/or via an epidural
chest closure as compression of the mediastinum catheter with a patient-regulated pain control sys-
by the donor allografts can result in hemodynamic tem. However, opioid-sparing pain regimens con-
compromise. During this time, patients should be sisting of agents such as acetaminophen,
kept sedated and maintained on MV. As gabapentin, and methocarbamol have been used
ischemia-reperfusion injury in PGD subsides, the with success.40 In addition, intraoperative lipo-
allografts become less edematous and are more somal bupivacaine intercostal nerve block and
easily accommodated by the closed chest cavity. intercostal cryoablation have been shown to
Similarly, a surgeon may choose to perform a par- reduce postoperative pain and opioid use after
tial or full lobar resection in cases of oversizing. lung transplantation and other procedures
Chest tubes are inserted intraoperatively into requiring a thoracotomy.40,41 Lastly, some trans-
each pleural cavity (usually two per side) and are plant centers may elect to place either paraverte-
placed under continuous suction to promote lung bral or epidural catheters for administration of
reexpansion and continued evacuation of pleural local anesthetic agents in an effort to minimize
fluid. A clamp trial to assess whether a chest postoperative opioid requirements,42–44 although
tube can be safely removed is generally performed complicated and often time-sensitive logistical
once there is complete resolution of any air leaks considerations at the time of transplant limit their
and after chest tube output falls below 100 to use.
150 mL in 24 h.
Both postural drainage and chest physio-
Overview of Induction and Maintenance
therapy can be routinely employed without
Immunosuppression
concern for mechanical complications at the bron-
chial anastomoses, and patients should perform As part of an induction immunosuppressive
incentive spirometry soon after extubation. Many regimen, corticosteroids are administered intrao-
transplant centers utilize devices that simulta- peratively at the time of allograft reperfusion, usu-
neously provide positive pressure, continuous ally as intravenous methylprednisolone 500 to
high-frequency oscillations, and aerosol delivery 1,000 mg. This is often followed by the administra-
to promote airway clearance and lung expan- tion of methylprednisolone 1 to 3 mg per kg daily
sion,36 although these devices should be used during the subsequent 3 days and then 0.5 to
with caution in patients with air leaks present in 0.8 mg per kg daily, which eventually is converted
their chest tube drainage systems because of to an equivalent oral prednisone dose that is
concern for pneumothorax. tapered over the ensuing weeks to months to a
Prophylactic broad-spectrum antibiotics with maintenance dose of 5 to 10 mg. Along with
activity against both gram-negative and gram- high-dose methylprednisolone, many centers
positive bacteria are administered in the first 48 currently use interleukin-2 receptor blockers
to 72 h after lung transplantation.37 Donor and (e.g., basiliximab) for induction immunosuppres-
recipient sputum, bronchial swab, and/or bron- sion, given as a fixed dose of 20 mg intraopera-
choalveolar lavage fluid cultures are acquired in tively and again 4 days postoperatively. A
the operating room and from bronchoscopies per- retrospective International Society of Heart and
formed in the first 24 to 48 h post-transplant, which Lung Transplantation (ISHLT) registry analysis
can help guide appropriate narrowing of antimi- demonstrated improved survival with the use of
crobial therapies. In addition, most transplant pro- IL-2 receptor antagonists in both single and bilat-
grams administer valganciclovir or ganciclovir for eral lung transplant recipients and with the use of
cytomegalovirus (CMV) prophylaxis if either the anti-thymocyte globulin (ATG), a less commonly
used cytolytic induction immunosuppressive transplantation, and chronic rejection in the subse-
agent, in bilateral lung transplant recipients.45 quent years following transplantation.1 However,
Maintenance immunosuppression after lung there are a multitude of early and late complica-
transplantation most commonly consists of three tions that can occur after lung transplantation.
different agents: a calcineurin inhibitor (either Here, we focus on early complications after lung
tacrolimus or cyclosporine), a cell cycle inhibitor transplantation often necessitating management
(either mycophenolate mofetil or azathioprine), in a critical care setting.
and a corticosteroid (initially methylprednisolone
and subsequently prednisone, as noted above).46 Primary graft dysfunction
Tacrolimus is typically dosed at approximately The largest contributor to early mortality after lung
0.1 mg per kg orally daily in two divided doses, transplantation is PGD.47 PGD is a form of
or as a single dose with the slow-release formula- ischemia-reperfusion injury occurring within 72 h
tion, and adjusted to maintain serum trough level after transplant that leads to increased capillary
concentrations of 8 to 15 ng/mL. Cyclosporine is permeability and noncardiogenic pulmonary
generally dosed at 5 mg per kg orally daily in two edema. Several mechanistic pathways have been
divided doses and adjusted to maintain serum implicated in the pathogenesis of PGD including
trough level concentrations of 250 to 350 ng/mL. endothelial dysfunction, the release of proinflam-
Mycophenolate mofetil is dosed at 1 to 3 gm daily matory cytokines and chemokines, innate immune
in two divided doses and azathioprine is dosed at dysfunction, and increased oxidative stress.25,48
1 to 2 mg/kg daily, although lower doses may be In 2005, the ISHLT proposed a standardized
required in patients who develop leukopenia as a PGD severity grading system based on the radio-
side effect. The role of mTOR inhibitors such as graphic presence or absence of alveolar infiltrates
sirolimus and everolimus after lung transplantation and the degree of gas exchange impairment,
merits further investigation. However, it is recom- quantified using a PaO2/FiO2 ratio (Table 1).49
mended that neither agent be used in the early This was subsequently updated in 2017 to also
postoperative period (i.e., less than 10 to 12 weeks) include an alternative grading schema using a ratio
because of concerns for impaired wound healing of SaO2/FiO2 in cases where PaO2 measurements
and bronchial anastomosis breakdown. cannot be obtained, with adjusted cutoffs
Several medications interact with calcineurin in- extracted from prior studies of ARDS (see Ta-
hibitors, and levels of tacrolimus and cyclosporine ble 1).50,51 Of note, both sets of guidelines
can either increase or decrease depending on the
nature of the drug–drug interaction. For example,
azoles, particularly voriconazole and posacona- Table 1
zole, cause a significant increase in serum con- Grading classification schema for primary graft
centrations of tacrolimus and cyclosporine. dysfunction
Cessation of these agents without an appropriate
Pulmonary
increase in a patient’s tacrolimus or cyclosporine Edema on
dose can cause dangerously low therapeutic con- PGD Chest PaO2/FiO2 SpO2/FiO2
centrations of these drugs. There are other Grade Radiograph Ratio Ratioa
commonly prescribed medications such as cal-
0 No >300 >315
cium channel blockers, macrolide antibiotics,
rifampin, anticonvulsants, and gastric motility 1 Yes >300 >315
agents shown to interact with calcineurin inhibi- 2 Yes 200–300 235–315
tors. Thus, consultation with either a pharmacist 3 Yes <200 <235
or a lung transplant physician may be necessary
Abbreviations: FiO2, fraction of inspired oxygen; PaO2,
to ensure immunosuppressive therapies are partial pressure of arterial oxygen; PGD, primary graft
dosed appropriately. Generally speaking, tacroli- dysfunction; SpO2, peripheral capillary oxygen saturation.
a
mus and cyclosporine levels should be monitored If PaO2 measurements are not available.
daily in the immediate postoperative period as Adapted from Christie JD, Carby M, Bag R, et al. Report
of the ISHLT Working Group on Primary Lung Graft
frequent dosing adjustments may be required.
Dysfunction part II: definition. A consensus statement of
the International Society for Heart and Lung Transplanta-
tion. J Heart Lung Transplant. 2005;24(10):1454-1459 and
Early Postoperative Complications
Snell GI, Yusen RD, Weill D, et al. Report of the ISHLT
The most frequent causes of mortality among lung Working Group on Primary Lung Graft Dysfunction, part
I: Definition and grading-A 2016 Consensus Group
transplant recipients are graft failure (including statement of the International Society for Heart and
PGD) during the first 30 days following transplan- Lung Transplantation. J Heart Lung Transplant.
tation, non-CMV infection in the first year following 2017;36(10):1097-1103.
emphasize the importance of excluding other dis- the prevention and treatment of PGD.64–67 In one
ease processes that could look radiographically randomized placebo-controlled trial, prophylactic
similar to PGD such as multifocal pneumonia or iNO initiated 10 min after reperfusion and
cardiogenic pulmonary edema. continued for a minimum of 6 h was not associated
PGD commonly occurs after lung transplanta- with improved clinical outcomes.64 In cases of re-
tion and has important prognostic implications. fractory hypoxemia because of severe PGD, how-
Specifically, grade 3 PGD is associated with signif- ever, iNO is an effective salvage therapy.65–67 VV
icantly longer ICU and hospital lengths of stay as ECMO is being increasingly utilized to support pa-
well as increased 90-day and 1-year mortality, tients who develop severe PGD after lung trans-
compared to absent or lower grades of plantation, with better outcomes reported if
PGD.47,51,52 Multiple studies have consistently ECMO is initiated early (ideally within the first
demonstrated an association between PGD and 24 h after transplantation).68–70 The rationale for
increased risk for the subsequent development starting earlier ECMO support is to prevent or mini-
of CLAD.53–55 Prior studies applying the standard- mize injury to the newly transplanted lung(s) from a
ized ISHLT classification system estimate an over- combination of high plateau pressures and excess
all PGD incidence of 30% and a grade 3 PGD PEEP and oxygen concentrations. In a 2007 ELSO
incidence of 15 to 20%.52,56,57 registry study, only 42% of patients with PGD
PGD generally develops within 48 h after lung requiring ECMO support survived to hospital
transplantation, whereas other radiographically discharge with death most commonly attributed
similar processes, such as acute rejection and to multiorgan failure,69 although outcomes have
infection, more commonly develop beyond the likely improved since then given clinical advances
first 48 h after transplant. Pulmonary venous anas- in ECLS. Lastly, re-transplantation in cases of very
tomotic complications (e.g., venous thrombosis, severe PGD is generally not advised because of
kinking, or external compression) can present poor survival outcomes.71
similarly, although these diagnoses can be
excluded by transesophageal echocardiography. Airway complications
Multiple risk factors have been associated with Anastomotic complications including ischemia
the development of PGD and can be subdivided and necrosis (Fig. 2A), dehiscence (Fig. 2B), ste-
into recipient-related, donor-related, periopera- nosis, and bronchial infection are common in the
tive, and postoperative risk factors first few weeks to months after lung transplanta-
(Table 2).47,51,52,56,58–62 tion, due in part to the lack or revascularization
Typical radiographic findings include perihilar of the bronchial circulation.72,73 One 2009 study
haziness, patchy alveolar consolidations, and, in reported anastomotic complications in 7 to 18%
its most severe form, dense perihilar and basilar of lung transplant recipients with an associated
alveolar consolidations with air bronchograms mortality of 2 to 4%.74 However, the incidence of
(Fig. 1). In addition, PGD can lead to a decrease in anastomotic complications has likely decreased
compliance and an increase in pulmonary vascular as surgical techniques have improved.
resistance. On histopathology, PGD can appear as Established risk factors for anastomotic compli-
diffuse alveolar damage based on reports from bi- cations after lung transplantation include peri- or
opsy specimens, autopsies, and lung explants postoperative hypotension, certain anastomotic
removed during re-transplantation; however, a bi- surgical techniques, right-sided anastomoses
opsy is rarely necessary to establish the diagnosis. (which are more than twice as likely to develop
PGD usually stabilizes within 2 to 4 days of onset airway complications compared to left-sided
and subsequently resolves, although in some cases anastomoses), length of the donor bronchus,
PGD can persist to varying degrees for days to PGD, acute cellular rejection, and microbiologic
weeks after lung transplantation. contamination, particularly with Aspergillus,
Treatment of PGD is primarily supportive, and Candida, Rhizopus, and Mucor species.73 Among
clinical management strategies have been mostly many but not all of these risk factors, reduced
extrapolated from existing ARDS literature. Thera- blood flow to the anastomosis is predominantly
pies with demonstrated benefits include lung- what compromises its integrity.
protective mechanical ventilation, diuretics, Early anastomotic complications generally
inhaled nitric oxide (iNO), and, in more severe occur within 4 to 12 weeks after lung transplanta-
cases, VV ECMO.47 Although low tidal volume tion and include partial or complete ischemia or
ventilation strategies are frequently utilized, set necrosis, bronchial dehiscence, and fungal and
tidal volumes often only take into consideration bacterial (usually Staphylococcus or Pseudo-
recipient characteristics and not donor character- monas species) infections. Bronchial dehiscence
istics.27,63 Use of iNO has been described for both should be suspected in patients with prolonged
Table 2
Clinical risk factors for the development of primary graft dysfunction
Category Risk Factor

52,56,58,59
Recipient-related risk factors Body mass index >25 kg/mg2
Diagnoses of IPF, PAH, and sarcoidosis
Elevated pulmonary artery pressure at time of transplant
Female sex
Left ventricular diastolic dysfunction
Donor-related risk factors52,56,60–62 Donor age extremes (i.e., pediatric donors and
age >55 years old)
African American race
Smoking history
Alcohol use
Head trauma
Chest trauma or lung contusion
Inhalation smoke exposure
Prolonged MV
Hemodynamic instability after brain death
Massive donor blood transfusion
Perioperative risk factors47,52 FiO2 >0.40 during allograft reperfusion
Single-lung transplantation
Intraoperative CPB
Use of Euro-Collins preservation solution
Prolonged ischemic time
Transfusion volume >1 liter
Delayed chest closure
Post-transplant risk factors51 Aspiration
Volume overload
Arterial and venous anastomotic complications
Hemodynamic instability
MV with large tidal volumes
Pneumonia
Abbreviations: FiO2, fraction of inspired oxygen; IPF, idiopathic pulmonary fibrosis; PAH, pulmonary arterial hypertension.
Adapted from refs 25,101
chest tube air leaks in the early post-transplant Bronchoscopic evaluation of anastomoses
period. Bronchial dehiscence can predispose pa- should assess for four main elements, per the
tients to serious infectious complications such as recently proposed ISHLT consensus guidelines:
empyema, mediastinitis, or the formation of a peri- ischemia and necrosis, dehiscence, stenosis,
bronchial abscess or fistula. and malacia.73 Standardized reporting of airway
The appearance of extraluminal air on chest CT complications allows clinicians to more easily
is very sensitive and specific for the diagnosis of track evolutionary changes over time in addition
anastomotic dehiscence.73 However, chest CT to providing better uniformity in research studies.
cannot reliably detect other early anastomotic During bronchoscopy, specimens from a bronchial
complications such as ischemic, necrosis, and wash or brush should be sent for culture and cyto-
infection. Rather, bronchoscopy is the preferred logic examination. If there is any evidence of infec-
method for comprehensively evaluating bronchial tion, appropriate antimicrobial therapies should be
anastomosis. It is often performed before post- initiated based on culture results.
transplant extubation, bearing in mind that Early anastomotic complications can predis-
ischemic changes can take several days to weeks pose patients to later complications such as bron-
to develop, and again before hospital discharge. chial stenosis, bronchomalacia, and the
Subsequent anastomotic complications are development of exophytic granulation tissue.
generally monitored during routine surveillance These conditions can manifest symptomatically
bronchoscopies that occur in the first year after as dyspnea at rest or on exertion, wheezing,
lung transplantation. cough, and/or worsening obstruction as
Fig. 1. Evolution of severe primary graft dysfunction following a right single-lung transplant for chronic obstruc-
tive pulmonary disease. Chest radiographs are shown at (A) baseline (i.e., immediately postoperatively), (B) 24 h,
(C) 48 h, and (D) 72 h after transplant. (From Lee JC, Christie JD. Primary graft dysfunction. Clin Chest Med.
2011;32(2):279-293.)100
documented by pulmonary function testing. Ther- procedures, and rarely surgery. Among lung trans-
apeutic options for anastomotic complications plant recipients who develop respiratory failure
include balloon dilation of a stricture, stent place- requiring intubation and mechanical ventilation,
ment, cryotherapy, argon beam coagulation, laser treating physicians should be aware of any
Fig. 2. Two examples of anastomotic complications following lung transplantation. (A) Circumferential airway
anastomotic necrosis extending >1 cm from the anastomosis to the bronchus intermedius. (B) Airway anasto-
motic necrosis along the membranous wall with a small area of dehiscence (indicated by the red arrow).
(Crespo MM, McCarthy DP, Hopkins PM, et al. ISHLT Consensus Statement on adult and pediatric airway com-
plications after lung transplantation: Definitions, grading system, and therapeutics. J Heart Lung Transplant
2018;37(5):548-563.)
anastomotic issues as these may alter diagnostic Bleeding and vascular complications
considerations and influence ventilatory Another complication of lung transplantation is
management. postoperative hemorrhage often requiring chest
re-exploration and washout. Early clues to this
Acute allograft rejection diagnosis include radiographic evidence of a
The three types of allograft rejection, categorized hemothorax (usually white-out of the hemithorax)
according to the timing of onset after lung trans- or a large volume of blood draining from the thor-
plantation and distinct histopathologic features, acostomy tubes. Risk factors include periopera-
are antibody-mediated rejection (AMR), which tive CPB, postoperative anticoagulation, and the
can rarely appear as a form of hyperacute rejec- presence of pleural adhesions from prior thoracic
tion, acute cellular rejection (ACR), and CLAD, surgeries or pleurodesis performed before lung
which can manifest as BOS and/or RAS. transplantation.79
Hyperacute rejection is a type of rapid-onset The start of postoperative hemorrhage is
AMR that generally occurs intraoperatively after frequently observed intraoperatively or in the first
allograft reperfusion. It is caused by preexisting 12 to 24 h after arrival to the ICU. The management
anti-human leukocyte antigen (HLA) antibodies should focus on adequate resuscitation, correct-
that bind to the donor vascular epithelium leading ing any associated coagulopathies, and trans-
to activation of complement, vessel thrombosis, fusing as indicated. However, if active bleeding
and allograft failure. Significant advancements in continues despite these measures, particularly if
HLA antibody testing have led to a dramatic reduc- bleeding results in hemodynamic instability and/
tion in the incidence of hyperacute rejection, which or multiple blood transfusion requirements, it is
now rarely occurs. imperative to take the patient back to the oper-
AMR occurs as a result of allospecific B cell and ating room for better source control to avoid com-
plasma cell production of antibodies directed plications associated with hemorrhagic shock or
against donor lung antigens. Antigen–antibody pulmonary complications related to excess blood
complex formation leads to the activation of products.
both complement-dependent and complement- In addition to the bronchial anastomotic compli-
independent pathways, resulting in acute allograft cations discussed earlier, vascular anastomotic
dysfunction. Despite recently proposed diagnostic complications can occur. Stenosis at the venous
criteria,75 establishing a clinical diagnosis of AMR anastomosis is suggested by new radiographic
can still be challenging, especially given that evidence of pulmonary edema and/or infiltrates.
donor-specific antibodies may not always be sero- This condition can be confused with PGD and is
logically present. Treatment of AMR includes a usually diagnosed by transesophageal echocardi-
combination of plasmapheresis, intravenous immu- ography (TEE). Stenosis at the arterial anasto-
noglobulin, proteasome inhibitors such as bortezo- mosis is suggested by unexplained gas
mib and carfilzomib, and/or rituximab, a exchange abnormalities and/or new or worsening
monoclonal antibody against the CD20 antigen. Of pulmonary hypertension.80 To minimize this
note, AMR is a well-described risk factor for CLAD.76 complication, the anesthesiologist and transplant
ACR is the far more common type of acute allo- surgeon should review the intraoperatively TEE
graft rejection, characterized by the presence of to assess the gradients and flow turbulence
perivascular and interstitial mononuclear cell infil- through each one of the venous anastomoses
trates that develop as a result of T lymphocyte before chest closure. If turbulent flows or elevated
recognition of foreign major histocompatibility com- peak systolic velocities are noted on TEE, surgical
plexes or other antigens.77 Approximately half of revision may be necessary.
lung transplant recipients will develop some degree
of ACR during the early months after transplant, Infectious complications
and as many as 90% of patients will experience Bacterial pneumonia is the most common life-
at least one episode of ACR within the first year.78 threatening infection that develops during the early
Notably, both ACR and AMR can present with postoperative period with an estimated incidence
varying degrees of severity. More severe cases as high as 35%.81–84 CMV is the most common
can be complicated by acute hypoxemic respira- type of viral infection seen with a 50% cumulative
tory failure requiring mechanical ventilation or incidence of viremia and/or tissue-invasive dis-
even ECMO support. Both entities, however, are ease.83–85 CMV can cause a wide spectrum of dis-
highly treatable, and ECMO should be considered eases, ranging from localized bronchial shedding
early in cases of rapidly escalating ventilatory re- or low-level viremia to widespread dissemination.
quirements to avoid ventilator-induced injury to The most common presentation of tissue-
the allograft(s). invasive CMV infection in lung transplant
recipients is pneumonitis, but it can also present megacolon, prolonged ileus, ischemic bowel,
as gastroenteritis, hepatitis, or colitis. Other vi- and pancreatitis.90
ruses that affect lung transplant recipients include Cardiac arrhythmias, particularly atrial arrhyth-
herpes simplex virus (especially early after trans- mias such as atrial fibrillation, are seen in 16 to
plant) and community-acquired respiratory viruses 46% of lung transplant recipients and are associ-
such as respiratory syncytial virus, parainfluenza, ated with an increase in hospital length of stay
influenza, human metapneumovirus, and adeno- and increased 1-year mortality.91,92 Risk factors
virus.86 Lastly, invasive fungal infections are include older age, right ventricular dysfunction or
more common among lung transplant recipients enlargement, elevated right atrial pressure, dia-
compared to other solid organ transplant recipi- stolic dysfunction, left atrial enlargement, and cor-
ents, with an overall incidence of 15 to 35.87,88 onary artery disease.92 One study demonstrated a
Such infections usually develop during the first 35% incidence of atrial fibrillation, which was
few months after transplant and are associated associated with older age and CPB, with a resul-
with significant morbidity and increased risk for tant increase in hospital length of stay but no in-
mortality. crease in mortality, ICU length of stay, or days
on MV.93 Early prophylactic administration of
beta blockers is common practice across many
Other early postoperative complications transplant centers.
Diaphragmatic paralysis because of phrenic nerve The hyperammonemia syndrome after lung
injury, which can occur in conjunction with other transplantation is a rare but potentially fatal
types of cardiothoracic surgery, is seen in 3 to complication, occurring in 1- to 4% of lung trans-
9% of lung transplant recipients and is associated plant recipients with a 75% risk for mortality.94,95
with prolonged mechanical ventilation, increased Previous reports have hypothesized that hyperam-
ICU length of stay, and higher rates of tracheos- monemia may be caused by an unmasking of a
tomy tube placement.89 An inability to wean a pa- partial urea cycle disorder under the metabolic
tient from mechanical ventilation may be indicative stress of transplant or may be related to immuno-
of phrenic nerve dysfunction, particularly in pa- suppressive agents, particularly calcineurin inhibi-
tients who underwent single-lung transplantation. tors, although its underlying pathophysiology
The diagnosis can be confirmed by phrenic nerve remains poorly understood. Infections because
conduction studies in mechanically ventilated of Mycoplasma hominis or Ureaplasma species,
patients or by fluoroscopic sniff test and/or often donor-acquired, have also been implicated
point-of-care ultrasound of the diaphragm in given these pathogens metabolize urea as an en-
non-mechanically ventilated patients. If the injury ergy source and produce ammonia as a byprod-
is a result of traumatic stretching of the phrenic uct. Early detection is crucial with daily
nerve but the nerve is not completely transected, monitoring of ammonia levels in the immediate
a slow recovery can be anticipated. Complete postoperative period, and management should
transection is rare, but the damage is permanent. be individualized based on clinical symptoms
In those cases, diaphragmatic plication or pacing and blood ammonia concentrations. Treatment
may be warranted. options include bowel decontamination, amino
Pleural effusions also commonly develop and/or acid supplementation, and, in severe cases, nitro-
persist after lung transplantation. These effusions gen scavenger therapy and RRT.
are usually lymphocyte-predominant exudates
and can be associated early on with rejection,
Intensive Care Unit Outcomes
infection, or severing of the lymphatics (i.e.,
chylous effusion). Other causes of pleural effu- In general, the number of lung transplant recipients
sions include heart failure, pulmonary embolism, who are admitted to the ICU is expected to in-
and trapped lung. Rarely pleurodesis or decortica- crease as the number of long-term survivors in-
tion may be required. crease. Early postoperative mortality rates have
Patients undergoing lung transplantation are declined dramatically because of improvements
also at risk for gastrointestinal complications. Spe- in surgical techniques and perioperative care,
cifically, lung transplant recipients experience with approximately 97% of lung transplant recipi-
higher rates of gastroparesis and severe gastro- ents surviving hospital discharge.96 However, after
esophageal reflux disease, resulting in an this immediate post-transplant period, lung trans-
increased risk for aspiration pneumonia. In addi- plant recipients are more likely than other solid or-
tion, there is a higher incidence of gastrointestinal gan transplant recipients to experience
emergencies such as colonic perforation, small complications such as infection or rejection that
bowel obstruction, diverticulitis, CMV colitis, necessitate readmission to the ICU.
Nearly 25% of lung transplant recipients require REFERENCES

an ICU admission after their initial hospital
discharge. The most common admission diagno- 1. Chambers DC, Cherikh WS, Harhay MO, et al. The
ses are acute respiratory failure and sepsis.97,98 international thoracic organ transplant registry of
The need for MV is common (over 50%), and mor- the international society for heart and lung trans-
tality rates are generally close to 40%. Prognostic plantation: thirty-sixth adult lung and heart-lung
factors for mortality include higher acute physi- transplantation report-2019; focus theme: donor
ology and chronic health evaluation scores, a and recipient size match. J Heart Lung Transplant
reduced FEV1, extrapulmonary organ dysfunction, 2019;38(10):1042–55.
low serum albumin level, longer duration of MV, 2. Chambers DC, Perch M, Zuckermann A, et al. The
and SLT.97–99 Patients admitted with a diagnosis international thoracic organ transplant registry of
of BOS who require MV are at particularly high the international society for heart and lung trans-
risk for death.97 Long-term survival among pa- plantation: thirty-eighth adult lung transplantation
tients who recover from an ICU stay is also report - 2021; focus on recipient characteristics.
compromised98 highlighting the clinical signifi- J Heart Lung Transplant 2021;40(10):1060–72.
cance of any ICU readmission in both the immedi- 3. Chiumello D, Coppola S, Froio S, et al. Extracorpo-
ate and distant future. real life support as bridge to lung transplantation: a
systematic review. Crit Care 22 2015;19(1):19.
4. Organ procurement and transplant network. Lung
SUMMARY allocation score (LAS) calculator. Available at. http://
optn.transplant.hrsa.gov/resources/allocation-
Over the past 40 years, outcomes after lung trans-
calculators/las-calculator/. Accessed April 27, 2021.
plantation have steadily improved likely as a result
5. Davis SQ, Garrity ER Jr. Organ allocation in lung
of better donor and recipient selection and ad-
transplant. Chest 2007;132(5):1646–51.
vances in clinical care. Despite this, lung trans-
6. Hayanga AJ, Aboagye J, Esper S, et al. Extracor-
plant recipients are at risk for numerous
poreal membrane oxygenation as a bridge to
complications many of which require management
lung transplantation in the United States: an
in an intensive care setting. In addition, changes in
evolving strategy in the management of rapidly
lung donor allocation have led to an increased
advancing pulmonary disease. J Thorac Cardio-
number of actively listed patients requiring
vasc Surg 2015;149(1):291–6.
advanced modalities of support while awaiting
7. Hayanga JWA, Hayanga HK, Holmes SD, et al. Me-
transplant. Thus, intensivists should maintain fa-
chanical ventilation and extracorporeal membrane
miliarity with core management principals relating
oxygenation as a bridge to lung transplantation:
to lung transplantation that frequently arise in the
closing the gap. J Heart Lung Transplant 2019;
critical care setting.
38(10):1104–11.
8. Hakim AH, Ahmad U, McCurry KR, et al. Contem-
CLINICS CARE POINTS porary outcomes of extracorporeal membrane
oxygenation used as bridge to lung transplanta-
tion. Ann Thorac Surg 2018;106(1):192–8.
9. Peek GJ, Mugford M, Tiruvoipati R, et al. Efficacy
ECMO can be used as a bridging strategy to and economic assessment of conventional ventila-
lung transplantation in select patient tory support versus extracorporeal membrane
populations. oxygenation for severe adult respiratory failure
PGD is a leading cause of early morbidity and (CESAR): a multicentre randomised controlled trial.
mortality after lung transplantation and ne- Lancet 2009;374(9698):1351–63.
cessitates urgent consideration of ECMO in 10. Burki NK, Mani RK, Herth FJF, et al. A novel extra-
severe cases. corporeal CO(2) removal system: results of a pilot
Bronchial anastomotic ischemia and necrosis study of hypercapnic respiratory failure in patients
can result in airway dehiscence and thus with COPD. Chest 2013;143(3):678–86.
require close monitoring with serial brochos- 11. Tiruvoipati R, Buscher H, Winearls J, et al. Early
copies. experience of a new extracorporeal carbon dioxide
removal device for acute hypercapnic respiratory
failure. Crit Care Resusc 2016;18(4):261–9.
12. Bermudez CA, Zaldonis D, Fan MH, et al. Pro-
DISCLOSURES longed use of the hemolung respiratory assist sys-
J G. Natalini and E S. Clausen have no relevant tem as a bridge to redo lung transplantation. Ann
conflicts of interest. Thorac Surg 2015;100(6):2330–3.
13. Downey P, Ragalie W, Gudzenko V, et al. Ambula- literature and rescue therapy options.
tory central veno-arterial extracorporeal membrane J Cardiothorac Vasc Anesth 2020;34(10):2766–75.
oxygenation in lung transplant candidates. J Heart 27. Beer A, Reed RM, Bölükbas S, et al. Mechanical
Lung Transplant 2019;38(12):1317–9. ventilation after lung transplantation. An interna-
14. Biscotti M, Gannon WD, Agerstrand C, et al. Awake tional survey of practices and preferences. Ann
extracorporeal membrane oxygenation as bridge Am Thorac Soc 2014;11(4):546–53.
to lung transplantation: a 9-year experience. Ann 28. Fan E, Del Sorbo L, Goligher EC, et al. An official
Thorac Surg 2017;104(2):412–9. American thoracic society/European society of
15. Fuehner T, Kuehn C, Hadem J, et al. Extracorporeal intensive care medicine/society of critical care
membrane oxygenation in awake patients as medicine clinical practice guideline: mechanical
bridge to lung transplantation. Am J Respir Crit ventilation in adult patients with acute respiratory
Care Med 2012;185(7):763–8. distress syndrome. Am J Respir Crit Care Med
16. Willers A, Swol J, Buscher H, et al. Longitudinal 2017;195(9):1253–63.
trends in bleeding complications on extracorporeal 29. Laghi F, Goyal A. Auto-PEEP in respiratory failure.
life support over the past two decades- Minerva Anestesiol 2012;78(2):201–21.
extracorporeal life support organization registry 30. Ahya VN, Kawut SM. Noninfectious pulmonary
analysis. Crit Care Med 2022. https://doi.org/10. complications after lung transplantation. Clin Chest
1097/CCM.0000000000005466. Med 2005;26(4):613–22, vi.
17. Nunez JI, Gosling AF, O’Gara B, et al. Bleeding and 31. Popple C, Higgins TL, McCarthy P, et al. Unilateral
thrombotic events in adults supported with venove- auto-PEEP in the recipient of a single lung trans-
nous extracorporeal membrane oxygenation: an plant. Chest 1993;103(1):297–9.
ELSO registry analysis. Intensive Care Med 2022; 32. Gavazzeni V, Iapichino G, Mascheroni D, et al. Pro-
48(2):213–24. longed independent lung respiratory treatment af-
18. Levin B, Ortoleva J, Tagliavia A, et al. One-year ter single lung transplantation in pulmonary
survival for adult venoarterial extracorporeal mem- emphysema. Chest 1993;103(1):96–100.
brane oxygenation patients requiring renal- 33. Anglès R, Tenorio L, Roman A, et al. Lung trans-
replacement therapy. J Cardiothorac Vasc Anesth plantation for emphysema. Lung hyperinflation:
2021. https://doi.org/10.1053/j.jvca.2021.12.027. incidence and outcome. Transpl Int 2005;17(12):
19. Thongprayoon C, Cheungpasitporn W, 810–4.
Lertjitbanjong P, et al. Incidence and impact of 34. Verleden GM, Glanville AR, Lease ED, et al.
acute kidney injury in patients receiving extracor- Chronic lung allograft dysfunction: definition, diag-
poreal membrane oxygenation: a meta-analysis. nostic criteria, and approaches to treatment-A
J Clin Med 2019;8(7). https://doi.org/10.3390/ consensus report from the Pulmonary Council of
jcm8070981. the ISHLT. J Heart Lung Transplant 2019;38(5):
20. St-Arnaud C, Thériault MM, Mayette M. North-south 493–503.
syndrome in veno-arterial extra-corporeal mem- 35. Hernández G, Vaquero C, González P, et al. Effect
brane oxygenator: the other Harlequin syndrome. of postextubation high-flow nasal cannula vs con-
Can J Anaesth 2020;67(2):262–3. ventional oxygen therapy on reintubation in low-
21. Falk L, Sallisalmi M, Lindholm JA, et al. Differential risk patients: a randomized clinical trial. JAMA
hypoxemia during venoarterial extracorporeal 2016;315(13):1354–61.
membrane oxygenation. Perfusion 2019;34(1_ 36. Esguerra-Gonzales A, Ilagan-Honorio M, Kehoe P,
suppl):22–9. et al. Effect of high-frequency chest wall oscillation
22. Choi JH, Kim SW, Kim YU, et al. Application of versus chest physiotherapy on lung function after
veno-arterial-venous extracorporeal membrane lung transplant. Appl Nurs Res 2014;27(1):59–66.
oxygenation in differential hypoxia. Multidiscip Re- 37. Okamoto K, Santos CAQ. Management and pro-
spir Med 2014;9(1):55. phylaxis of bacterial and mycobacterial infections
23. Hayanga JW, D’Cunha J. The surgical technique of among lung transplant recipients. Ann Transl Med
bilateral sequential lung transplantation. J Thorac 2020;8(6):413.
Dis 2014;6(8):1063–9. 38. Kotton CN, Kumar D, Caliendo AM, et al. The third
24. Weingarten N, Schraufnagel D, Plitt G, et al. Com- international consensus guidelines on the manage-
parison of mechanical cardiopulmonary support ment of cytomegalovirus in solid-organ transplan-
strategies during lung transplantation. Expert Rev tation. Transplantation 2018;102(6):900–31.
Med Devices 2020;17(10):1075–93. 39. Husain S, Camargo JF. Invasive aspergillosis in
25. Natalini JG, Diamond JM. Primary graft dysfunction. solid-organ transplant recipients: guidelines from
Semin Respir Crit Care Med 2021;42(3):368–79. the American society of transplantation infectious
26. Ortoleva J, Shapeton A, Vanneman M, et al. Vaso- diseases community of practice. Clin Transplant
plegia during cardiopulmonary bypass: current 2019;33(9):e13544.
40. Lewis TC, Sureau K, Katz A, et al. Multimodal 53. Daud SA, Yusen RD, Meyers BF, et al. Impact of im-
opioid-sparing pain management after lung trans- mediate primary lung allograft dysfunction on bron-
plantation and the impact of liposomal bupivacaine chiolitis obliterans syndrome. Am J Respir Crit Care
intercostal nerve block. Clin Transplant 2022;36(1): Med 2007;175(5):507–13.
e14512. 54. Fisher AJ, Wardle J, Dark JH, et al. Non-immune
41. Yasin J, Thimmappa N, Kaifi JT, et al. CT-guided acute graft injury after lung transplantation and
cryoablation for post-thoracotomy pain syndrome: the risk of subsequent bronchiolitis obliterans syn-
a retrospective analysis. Diagn Interv Radiol drome (BOS). J Heart Lung Transplant 2002;
2020;26(1):53–7. 21(11):1206–12.
42. McLean SR, von Homeyer P, Cheng A, et al. As- 55. Whitson BA, Prekker ME, Herrington CS, et al. Pri-
sessing the benefits of preoperative thoracic mary graft dysfunction and long-term pulmonary
epidural placement for lung transplantation. function after lung transplantation. J Heart Lung
J Cardiothorac Vasc Anesth 2018;32(6):2654–61. Transplant 2007;26(10):1004–11.
43. Hutchins J, Apostolidou I, Shumway S, et al. Para- 56. Diamond JM, Arcasoy S, Kennedy CC, et al.
vertebral catheter use for postoperative pain con- Report of the international society for heart and
trol in patients after lung transplant surgery: a lung transplantation working Group on primary
prospective observational study. J Cardiothorac lung graft dysfunction, part II: epidemiology, risk
Vasc Anesth 2017;31(1):142–6. factors, and outcomes-A 2016 consensus Group
44. Murray AW, Boisen ML, Fritz A, et al. Anesthetic statement of the international society for heart
considerations in lung transplantation: past, pre- and lung transplantation. J Heart Lung Transplant
sent and future. J Thorac Dis 2021;13(11): 2017;36(10):1104–13.
6550–63. 57. Christie JD, Bellamy S, Ware LB, et al. Construct
45. Hachem RR, Edwards LB, Yusen RD, et al. The validity of the definition of primary graft dysfunction
impact of induction on survival after lung transplan- after lung transplantation. J Heart Lung Transplant
tation: an analysis of the International Society for 2010;29(11):1231–9.
Heart and Lung Transplantation Registry. Clin 58. Porteous MK, Ky B, Kirkpatrick JN, et al. Diastolic
Transplant 2008;22(5):603–8. dysfunction increases the risk of primary graft
46. Levine SM. A survey of clinical practice of lung dysfunction after lung transplant. Am J Respir Crit
transplantation in North America. Chest 2004; Care Med 2016;193(12):1392–400.
125(4):1224–38. 59. Porteous MK, Lee JC, Lederer DJ, et al. Clinical
47. Shah RJ, Diamond JM. Primary graft dysfunction risk factors and prognostic model for primary graft
(PGD) following lung transplantation. Semin Respir dysfunction after lung transplantation in patients
Crit Care Med 2018;39(2):148–54. with pulmonary hypertension. Ann Am Thorac Soc
48. Schnickel GT, Ross DJ, Beygui R, et al. Modified 2017;14(10):1514–22.
reperfusion in clinical lung transplantation: the re- 60. de Perrot M, Bonser RS, Dark J, et al. Report of the
sults of 100 consecutive cases. J Thorac Cardio- ISHLT working Group on primary lung graft
vasc Surg 2006;131(1):218–23. dysfunction part III: donor-related risk factors and
49. Christie JD, Carby M, Bag R, et al. Report of the markers. J Heart Lung Transplant 2005;24(10):
ISHLT working Group on primary lung graft 1460–7.
dysfunction, part II: definition — a consensus state- 61. Borders CF, Suzuki Y, Lasky J, et al. Massive donor
ment of the international society for heart and lung transfusion potentially increases recipient mortality
transplantation. J Heart Lung Transplant 2005; after lung transplantation. J Thorac Cardiovasc
24(10):1454–9. Surg 2017;153(5):1197–203.e2.
50. Rice TW, Wheeler AP, Bernard GR, et al. Compari- 62. Pelaez A, Mitchell PO, Shah NS, et al. The role of
son of the SpO2/FIO2 ratio and the PaO2/FIO2 ratio donor chronic alcohol abuse in the development
in patients with acute lung injury or ARDS. Chest of primary graft dysfunction in lung transplant re-
2007;132(2):410–7. cipients. Am J Med Sci 2015;349(2):117–23.
51. Snell GI, Yusen RD, Weill D, et al. Report of the 63. Currey J, Pilcher DV, Davies A, et al. Implementa-
ISHLT working Group on primary lung graft tion of a management guideline aimed at mini-
dysfunction, part I: definition and grading-A 2016 mizing the severity of primary graft dysfunction
consensus Group statement of the international so- after lung transplant. J Thorac Cardiovasc Surg
ciety for heart and lung transplantation. J Heart 2010;139(1):154–61.
Lung Transpl 2017;36(10):1097–103. 64. Meade MO, Granton JT, Matte-Martyn A, et al.
52. Diamond JM, Lee JC, Kawut SM, et al. Clinical risk A randomized trial of inhaled nitric oxide to prevent
factors for primary graft dysfunction after lung ischemia-reperfusion injury after lung transplanta-
transplantation. Am J Respir Crit Care Med 2013; tion. Am J Respir Crit Care Med 2003;167(11):
187(5):527–34. 1483–9.
65. Date H, Triantafillou AN, Trulock EP, et al. Inhaled 79. Oechslin P, Zalunardo MP, Inci I, et al. Established
nitric oxide reduces human lung allograft dysfunc- and potential predictors of blood loss during lung
tion. J Thorac Cardiovasc Surg 1996;111(5):913–9. transplant surgery. J Thorac Dis 2018;10(6):3845–8.
66. Adatia I, Lillehei C, Arnold JH, et al. Inhaled nitric 80. Siddique A, Bose AK, Özalp F, et al. Vascular anas-
oxide in the treatment of postoperative graft tomotic complications in lung transplantation: a sin-
dysfunction after lung transplantation. Ann Thorac gle institution’s experience. Interact Cardiovasc
Surg 1994;57(5):1311–8. Thorac Surg 2013;17(4):625–31.
67. Macdonald P, Mundy J, Rogers P, et al. Successful 81. Fishman JA. Infection in solid-organ transplant re-
treatment of life-threatening acute reperfusion injury cipients. N Engl J Med 2007;357(25):2601–14.
after lung transplantation with inhaled nitric oxide. 82. Lease ED, Zaas DW. Complex bacterial infections
J Thorac Cardiovasc Surg 1995;110(3):861–3. pre- and posttransplant. Semin Respir Crit Care
68. Wigfield CH, Lindsey JD, Steffens TG, et al. Early Med 2010;31(2):234–42.
institution of extracorporeal membrane oxygena- 83. Burguete SR, Maselli DJ, Fernandez JF, et al. Lung
tion for primary graft dysfunction after lung trans- transplant infection. Respirology 2013;18(1):22–38.
plantation improves outcome. J Heart Lung 84. Remund KF, Best M, Egan JJ. Infections relevant to
Transplant 2007;26(4):331–8. lung transplantation. Proc Am Thorac Soc 2009;
69. Fischer S, Bohn D, Rycus P, et al. Extracorporeal 6(1):94–100.
membrane oxygenation for primary graft dysfunction 85. Zamora MR, Davis RD, Leonard C. Management of
after lung transplantation: analysis of the Extracorpo- cytomegalovirus infection in lung transplant recipi-
real Life Support Organization (ELSO) registry. ents: evidence-based recommendations. Trans-
J Heart Lung Transplant 2007;26(5):472–7. plantation 2005;80(2):157–63.
70. Bermudez CA, Adusumilli PS, McCurry KR, et al. 86. Kumar D, Erdman D, Keshavjee S, et al. Clinical
Extracorporeal membrane oxygenation for primary impact of community-acquired respiratory viruses
graft dysfunction after lung transplantation: long- on bronchiolitis obliterans after lung transplant.
term survival. Ann Thorac Surg 2009;87(3): Am J Transplant 2005;5(8):2031–6.
854–60. 87. Hosseini-Moghaddam SM, Husain S. Fungi and
71. Kawut SM, Lederer DJ, Keshavjee S, et al. Outcomes molds following lung transplantation. Semin Respir
after lung retransplantation in the modern era. Am J Crit Care Med 2010;31(2):222–33.
Respir Crit Care Med 2008;177(1):114–20. 88. Solé A, Salavert M. Fungal infections after lung trans-
72. Machuzak M, Santacruz JF, Gildea T, et al. Airway plantation. Curr Opin Pulm Med 2009;15(3):243–53.
complications after lung transplantation. Thorac 89. Ferdinande P, Bruyninckx F, Van Raemdonck D,
Surg Clin 2015;25(1):55–75. et al. Phrenic nerve dysfunction after heart-lung
73. Crespo MM, McCarthy DP, Hopkins PM, et al. and lung transplantation. J Heart Lung Transplant
ISHLT Consensus Statement on adult and pediatric 2004;23(1):105–9.
airway complications after lung transplantation: 90. Lyu DM, Zamora MR. Medical complications of lung
Definitions, grading system, and therapeutics. transplantation. Proc Am Thorac Soc 2009;6(1):101–7.
J Heart Lung Transplant 2018;37(5):548–63. 91. Roukoz H, Benditt DG. Atrial arrhythmias after lung
74. Santacruz JF, Mehta AC. Airway complications and transplantation. Trends Cardiovasc Med 2018;
management after lung transplantation: ischemia, 28(1):53–61.
dehiscence, and stenosis. Proc Am Thorac Soc 92. Orrego CM, Cordero-Reyes AM, Estep JD, et al.
2009;6(1):79–93. Atrial arrhythmias after lung transplant: underlying
75. Levine DJ, Glanville AR, Aboyoun C, et al. Anti- mechanisms, risk factors, and prognosis. J Heart
body-mediated rejection of the lung: a consensus Lung Transplant 2014;33(7):734–40.
report of the international society for heart and 93. Raghavan D, Gao A, Ahn C, et al. Contemporary
lung transplantation. J Heart Lung Transplant analysis of incidence of post-operative atrial fibrilla-
2016;35(4):397–406. tion, its predictors, and association with clinical
76. Witt CA, Gaut JP, Yusen RD, et al. Acute antibody- outcomes in lung transplantation. J Heart Lung
mediated rejection after lung transplantation. Transplant 2015;34(4):563–70.
J Heart Lung Transplant 2013;32(10):1034–40. 94. Leger RF, Silverman MS, Hauck ES, et al. Hyper-
77. Stewart S, Fishbein MC, Snell GI, et al. Revision of ammonemia post lung transplantation: a review.
the 1996 working formulation for the standardization Clin Med Insights Circ Respir Pulm Med 2020;14.
of nomenclature in the diagnosis of lung rejection. 1179548420966234.
J Heart Lung Transplant 2007;26(12):1229–42. 95. Krutsinger D, Pezzulo A, Blevins AE, et al. Idiopathic
78. Martinu T, Howell DN, Palmer SM. Acute cellular hyperammonemia after solid organ transplantation:
rejection and humoral sensitization in lung trans- primarily a lung problem? A single-center experi-
plant recipients. Semin Respir Crit Care Med ence and systematic review. Clin Transplant 2017;
2010;31(2):179–88. 31(5). https://doi.org/10.1111/ctr.12957.
96. Scientific Registry of Transplant Recipients. Patient requiring admission to the medical ICU. Chest
survival after lung transplantation. Available at: 2014;146(3):590–9.
http://www.srtr.org. Accessed December 14, 2015. 99. Hadjiliadis D, Steele MP, Govert JA, et al. Outcome
of lung transplant patients admitted to the medical
97. Cohen J, Singer P, Raviv Y, et al. Outcome of lung
ICU. Chest 2004;125(3):1040–5.
transplant recipients requiring readmission to the
100. Lee JC, Christie JD. Primary graft dysfunction. Clin
intensive care unit. J Heart Lung Transplant 2011;
Chest Med 2011;32(2):279–93.
30(1):54–8.
101. Porteous MK, Lee JC. Primary graft dysfunction af-
98. Banga A, Sahoo D, Lane CR, et al. Characteristics ter lung transplantation. Clin Chest Med 2017;
and outcomes of patients with lung transplantation 38(4):641–54.

Critical Care Management of The Lung Transplant Recipient

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Critical Care Management of The Lung Transplant Recipient

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C r i t i c a l C a re M a n a g e m e n t

INTRODUCTION such as primary graft dysfunction (PGD), acute

Clin Chest Med 44 (2023) 105–119

Bridging to Lung Transplantation in an severe bronchiectasis, lower-flow platforms such

Category Risk Factor

Nearly 25% of lung transplant recipients require REFERENCES

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