You are on page 1of 16

284

Review Article
Periopcrativc anaesthetic
considerations for
patients undergoing
Harbhej Singh MO FFARCSI,
lung transplantation Robert F Bossard MD

Purpose: Five thousand, two hundred and eight lung transplants were performed worldwide before April, 1996.
This review will discuss lung transplantation from an historical perspective, its indications, donor and recipient
selection criteria, donor lung preparation, su~cal considerations, perioperative anaesthetic management, and
associated morbidity and mortality.
Source: Recent literature on perioperative anaesthetic management of lung transplantation and experience from
international centres including the Toronto Lung Transplant Group and the St. Louis Lung Transplant Group.
Principal fiadings: Lung transplantation comprises of a family of operations, including single lung transplant, bilat-
eral single lung transplant, lobar transplant and block heart-lung transplant. Improved donor lung preservation tech-
niques have increased the duration of cold ischaemictime. The advent of bilateral single lung transplant has decreased
the requirement for cardiopulmonary bypass, and airway complications have been reduced by adoption of~e tele-
scoping bronchial anastomoses. Advances in perioperative monitoring (including transoesophgeai echocardiogra-
phy), pulmonary vasodilators (e.g., nitric oxide and prostaglandin El), carcliopulmonary bypass and ventilatory
management, and a better understanding of the pathophysiological processes during the procedure have improved
perioperative anaesthetic management. Also, advances in broad spectrum antibiotics and immunosuppressant drugs
have improved the outcome by better management of the complications of infection and rejection.
Conclusion: Lung transplantation improves the quality of life with marginal improvement in life expectancy of the
recipients. It is an expensive procedure requiring continued resources for long term management of these patients.
Objectif : jusqu'en avril 1996, cinq mille, deux cent huit transplantations de poumons avaient dEj,~Et~ effectuL~,s
,~travers le monde. Ce survol permettra de discuter de la transpl@~tion pulmonalre darts sa perspective historique,
ses indications, les crit&es de s~lection du receveur et du donneur, la preparation du poumon du donneur, les con-
sid&ations chirurgicales, la gestion p&iol~ratoire de ranesth~sie et la mortaiit~ et la morbidit~ assod~es.
Source : Les publications r&entes traitant de la gestion p&iop&atoire de la transplantation pulmonaire et de
l'exl:~rience acquise par des centres intemationaux dont le Toronto Lung Transplant Group et le St.Louis Lung
Transplant Group.
Princlpales r : la transplantation pulmonaire englobe une famille d'interventions dont la trans-
plantation unipulmonaire, bilat&ale simple, Iobaire et coeur-poumons en bloc. I:am61ioration des techniques de
pr6servation des poumons du donneur a permis ram~lioration de la durEe de risch6mie froide. I'av~nement de
la transplantation bilat~rale simple a rEduit la n~cessitE de la circulation extracorporelle et rintroduction des anas-
tomoses t~lescopiques a permis de r~duire les complications particuli&es aux voles a~dennes. Le perfection-
nement du monitorage p~nop&atoire (dont r&hographie transoesophagienne), des vasoclilatateurs pulmonaires
(par ex.. roxyde nitrique et la prostaglandine E I), de la gestion de la circulation extracorporelle et de la ventila-
tion, et une meilleure connaissance du processus, physiopathologlque propre ,~ I'intervention ont pennis
d'am~liorer la conduite anesthEsique pEdop&atoire. Egalement, les progr~s n~alis~ dans rantibioth&ap~e h large
spectre autorisent un pronostic plus favorable g~ce ,~ un meilleur contr61e de rinfection et du rejet.
C o n d u s i o n : La transplantation pulmonaire an~liore consid&ablement la qualit~ de vie mais marginaJement rexpec-
tative vitale. Elle coOte cher et requiert des ressources continues pour la prise en charge ,~ long terme des transplant&.

From the Department of Anesthesiology and Pain Management, University of Texas Soudawestern Medical Center, 5323 Harry Hines Bird,
Dallas, Texas 75235-9068, USA.
Address correspondence to: Harbhej Singh MD, I~ARCSl.Phone: 972-432-974:1; Fax: 214-648-7660.
Aceopted for publicu~ion October 3, 1996.

CAN J ANAESTH 1997 / 44:3 / pp 284-299


Singh & Bossard: ANAESTHESIAAND LUNGTRANSPLANTATION 285

Contents Historical perspective


I. Historical Perspective In 1963, James Hardy performed the first human lung
transplant in a 58-yr-old patient with bronchogenic car-
II. Choice of Operation cinoma,s Although the patient survived for only 18
III. Recipient Selection days, the technical and functional feasibility of this pro-
IV. Preoperative Evaluation cedure stimulated an international interest in lung
V. Donor Selection transplantation. Unfortunately, a majority of the initial
recipients experienced either early rejection or bronchial
VI. Donor Lung Preparation dehiscence, longest survival being eight months. 4 This
VII. Surgical Considerations poor outlook began to change in 1983 when the
VIII. Preoperative and Intraoperative Anaesthetic Toronto Lung Transplant Group performed the first
Management successful SLT utilizing omental wrapping around the
A. Preoperative Preparation and Monitoring bronchial anastomosis in a patient with severe idiopath-
B. Induction and Maintenance ic pulmonary fibrosis, s Subsequently, DLTs, HLTs and
C. Special Intraoperative Considerations BSLTs were introduced into clinical practice.
IX. Postoperative Management
A. Ventilatory Management Choice o f operation
B. Pulmonary Reimplantation Response The pathology in patients with ESLD for lung trans-
C. Ventilatory Response plantation includes obstructive lung disease (chronic
D. Haemodynamic and Fluid Management obstructive pulmonary disease), restrictive lung disease
E. Pain Management (pulmonary fibrosis), infectious lung disease (cystic
F. Antimicrobials and Immunosuppression fibrosis) and pulmonary vascular disease (pulmonary
X. Delayed Complications After Lung hypertension).
Transplantation Chronic obstructive pulmonary disease (COPD) is
A. Infection the most common indication for performing lung trans-
B. Acute Rejection and Obliterative plant. 1 Others are listed in Table I. 1 Single lung trans-
Bronchiolitis plant, initially restricted to patients with end-stage
C. Causes of Death pulmonary fibrosis, has now been performed successful-
XI. Anaesthesia in Patients with Lung Transplant ly in patients with COPD, primary pulmonary hyper-
tension, and Eisenmenger's syndrome.6-s Fibrotic lung
XII. Patients Survival and Future Directions
disease is considered an ideal indication for SLT as both
XIII. Summary the ventilation and perfusion are distributed preferen-
XIV. Acknowledgments tially to the transplanted lung which is more compliant
XV. References and has lower pulmonary vascular resistance (PVR).9
Single lung transplant, bilateral single lung trans-
plant and heart-lung transplant can be performed for
UNG transplantation has gained acceptance pulmonary hypertension. Improvement in right ven-

L as a viable surgical procedure during the last


decade for patients with end-stage lung dis-
ease (ESLD). Data from the St. Louis
International Lung Transplant Registry show a total of
5208 lung transplants performed before April 1, 1996.
tricular (RV) structure and function after SLT for

TABLE 1 Indicationsfor LungTransplantsby Diagnosis1


Indication ~o/n (Total) *
Of these, 3145 were single lung transplants (SLTs),
1809 bilateral/sequential single lung transplants Chronic ObstructivePulmonaryDisease(COPD) 39%
(BSLTs), and 243 en-bloc double lung transplants Idiopathic PulmonaryFibrosis (IPF) 16%
CysticFibrosis (CF) 14%
(DLTs). l Of the 200 paediatric transplants performed PrimaryPulmonaryHypertension(PPH) 7%
before April 1, 1996, 36 were SLTs, 146 were BSLTs, Bronchiectasis 3%
and 17 were DLTs. 1 Despite the progressively increas- Retransplantation 3%
ing number of lung transplants performed each year, Eisenmenger'sDisease 2%
the number of recipients awaiting lung transplants has BronchiolifisObliterans(BO) 2%
increased.2 In contrast, the number of heart-lung trans- Other (specified) 10%
Other (unspecified) 4%
plants (HLTs) performed each year has declined with
the introduction of SLTs and BSLTs.2 *Valuesare percentageof total number(n=5208)
286 CANADIANJOURNALOF ANAESTHESIA

primary ptdmonary hypertension has been demonstrat- patients with systemic disease with pulmonary manifes-
ed by 2-D and Doppler echocardiography in a series of tations, selection should be confined to those with
14 patients. 7 The RV dimensions decreased and ejec- pathology principally in the lungs) s Renal or hepatic
tion fraction increased in all the patients in the early insufficiency is a contraindication as adverse effects of
post-transplant period (<three months). A later follow immunosuppressive agents may exacerbate renal or
up (six months to two years) of 12 patients demon- hepatic impairment. Although multi-organ failure has
strated decrease in right ventricular wall thickness in 10 been considered a contraindication to transplantation,
patients. 7 However, SLT for pulmonary hypertension is multi-organ transplants have been performed. 14
characterized by a high incidence of early (reperfusion Malignancy is a contraindication because of the risk of
injury) and late complications (V/Q mismatch). 1~ reactivation with immunosuppression. In the presence
Bando et al. demonstrated higher mortality, prolonged of malignancy, the disease-free interval before trans-
ICU stay, and less symptomatic improvement following plantation varies according to the primary site and
SLT in a series of 48 pulmonary hypertension recipi- should be considered individually in each patient. 14
ents) ~ Therefore, despite a shortage of donor organs, The nutritional status of the recipients should be
SLT may not be the procedure of choice for patients adequate: severe cachexia and morbid obesity are con-
with pulmonary hypertension, and outcome studies traindications. 14 Smokers should be free from smoking
comparing SLT and BSLT for pulmonary hypertension for 6-12 mo before transplantation. 14 A recipient
are needed. should also exhibit a stable psychosocial profile with-
Bilateral single lung transplant is considered the out alcohol or drug dependence. Major psychiatric ill-
procedure of choice for cystic fibrosis and bronchiec- ness is usually considered a contraindication. 14
tasis to prevent the spread of infection from the native Dependence on corticosteroids was considered a
into the transplanted lung. However, SLT has been contraindication to pulmonary transplantation.
successful in these patients, u Cystic fibrosisis is the Patients were required to discontinue steroid therapy
most common indication for paediatric lung trans- before surgery as steroids were presumed to inhibit
plantation (Table II). 1 Current indications for HLT healing of the airway anastomosis, is However, patients
are limited to patients with congenital heart disease receiving perioperative steroids have undergone suc-
and/or left ventricular dysfunction with associated cessful transplantation without increased anastomotic
pulmonary disease. Heart-lung transplant is associated or wound complications. 6 Early use of corticosteroids
with an increased incidence of graft rejection or oblit- in the posttransplant period may benefit some patients
erative bronchiolitis (OB), development of accelerated by improving bronchial healing and reducing the inci-
coronary artery disease and complications related to dence of stenotic complications. 6 Schafers et ul. did
cardiopulmonary bypass (CPB). 12 not find increased morbidity or mortality following
lung transplantation in patients receiving preoperative
prednisone up to 0.3 mg.kg-l-day-k 16 Patients receiv-
Recipient selection
ing preoperative prednisone should be able to tolerate
Although selection criteria may vary between centres,
a reduction in the dose to 15 mg.day-1 before trans-
patients generally have irreversible and progressive pul- plantation, x4
monary disease requiring O 2 therapy and an anticipated
Ventilator-dependent patients were considered
life expectancy <18 too. 6,13 The upper age limit for
unsuitable candidates for transplantation because of the
recipients varies as biological rather than chronological
risk of airway colonization leading to nosocomial infec-
age is of more importance. Keeipients >60 yr have been
tions, and accompanying muscle deconditioning and
accepted in the absence of other complications, t4 In
multi-organ failure. 14 However, carefully selected
patients have been transplanted successfully without
TABLE 2 Indicationsfor PaediatricTransplants by Diagnosisl increased postoperative morbidity or mortality. In a
Indication %/n (Total) * series of 10 ventilator-dependent patients, the postop-
erative course and infectious and rejection complica-
Cystic Fibrosis(CF) 46% tions were similar to those of spontaneously breathing
Primary PulmonaryHypertension (PPH) 15%
Idiopathic PulmonaryFibrosis (IPF) 7% patients undergoing lung transplantation. 17 In another
Bronchiolitis Obliterans (BO) 5% series of patients tmdergoing DLT, pretransplantation
Retransplantation 5% ventilation did not prolong the posttransplantation
Eisenmenger's Disease 5% hospital stay of these patients, is Recently, patients treat-
Other 17% ed with extracorporeal membrane oxygenation have
*Valuesare percentage of total number (n=200) also undergone successful lung transplantation. 19
Singh & Bossard: ANAESTHESIAAND LUNGTRANSPLANTATION 287

Preoperative evaluation Haematological and biochemical screening is per-


Upon satisfying the recipient selection criteria, thor- formed to assess other organ system fmaction. A
ough history, physical examination and laboratory stud- Mantoux skin test detects previous tuberculosis exposure
ies are performed. These patients frequently are oxygen and immunological screening determines ABO group,
dependent and severely limited in their mobility and human-immunodeficiency virus (HIV) serology, hepati-
ability to perform even the routine tasks of daily living, is tis B surface antigen (HBsAg) and cytomegalovirus
Preoperative assessment is directed to ascertain fight (CMV) status. 14 Recipients with positive HIV serology
and left ventricular function, presence or absence of pul- are unsuitable for lung transplantation due to increased
monary hypertension, degree of obstructive airway dis- risk from added immunosuppression.
ease, exercise tolerance, and other major organ system
functions. Evaluation includes a battery of pulmonary Donor selection
function testing, cardiac evaluation, and haematological, Despite the shortage of donor lungs, only lungs from
biochemical and immunological studies. suitable perfused organ donors are accepted for trans-
Pulmonary testing at our institution includes exer- plantation as status of the implanted lung is one of the
cise tolerance (a treadmill walking protocol), pul- important predictors of outcome. 6 The majority of
monary function tests with DLCO and ABG, chest CT donors are victims of gunshot wounds (31%), intracra-
without contrast, and quantitative V / Q scan if indi- nial haemorrhage (24%), and motor vehicle accidents
cated. Cardiac studies include 2-D echocardiogram (21%). 1 Only 5-10% of perfused organ donors have
with Doppler estimation of pulmonary artery pressure, lungs acceptable for transplantation, as either direct
multiple uptake gated acquisition scan and cardiac (trauma-related) or indirect (aspiration, infection, neu-
catheterization to determine right and left ventricular rogenic pulmonary oedema) injuries render them
function. Coronary angiography may be performed unsuitable for transplantation. 23 Pulmonary "twinning"
even in asymptomatic patients >45 yr with negative or the use of one donor lung block for SLTs in two
non-invasive testing, la Routine angiography for exclu- recipients has increased the donor lung pool and low-
sion of asymptomatic coronary artery disease (CAD) in ered the cost of retrieval per lung. 24In urgent situations,
patients with a history of smoking has not been shown such as in infants requiring extracorporeal membrane
to be justified. Patients identified as high risk by the oxygenation, lobar transplantation (living related or
presence of additional CAD risk factors may benefit cadaveric) is an alternative in the environment of donor
from coronary angiography. 2~ Right ventricular func- lung shortage. 2s Also, bilateral lobar transplantation
tion can be compromised by ESLD. Right ventricular may be an option for patients with cystic fibrosis and
ejection fraction (RVEF) <20% may be considered the life-threatening respiratory decompensation. 2s
lowest acceptable limit for successful transplantation. 9 The majority of suitable donors are <55 yr without
This lower acceptable limit ofpreoperable RV function pulmonary trauma or severe preexisting lung dis-
is somewhat arbitrary since improvement in RV func- ease. 26,27Serial chest X-rays should be free from acute or
tion has been reported following lung transplantation. 7 chronic parenchymal lung disease. 26 Bronchoscopic
As echocardiographic examination for assessment of examination including Gram's stain of the bronchial
RV size or function may be suboptimal, techniques washings should be normal. 26 Some centres accept
such as ultrafast CT has been suggested as an alterna- donors up to 60 yr, and a smoking history is acceptable
tive for quantitative assessment of ventricular volume unless the donor has chronic obstructive pulmonary
and function for preoperative evaluation. 21 In patients disease or pulmonary fibrosis. 27,2s Oxygenation should
with pulmonary hypertension, preoperative transoe- be satisfactory, i.e., PaO 2 >300 mmHg breathing FiO 2
sophageal echocardiography (TEE) has been shown to 1.0 with 5 mmHg PEEP or PaO2>100 mmHg with
provide additional diagnostic information tmdetected FiO 2 0.4. 26;s Donor lungs are matched with recipients
by right and left heart catheterization, transthoracic within the same ABO group. 26 Human leukocyte anti-
echocardiography, or radionuclide ventriculography. gen (HLA) matching is not performed because the
The additional information obtained [proximal pul- lungs can deteriorate during the time required for
monary artery emboli (three), patent foramen ovale matching and HLA matching has not been shown to
with right to left shunting (two), atrial septal defect correlate with the frequency of chronic rejection. 29
(two), double-outlet fight ventricle (two), ventricular Where possible, CMV serology should be negative or
septal defect (two), and exclusion of atrial septal defect identical to that of the recipient. 3~However, recent data
(one)] altered the assignment of surgical therapy in from the St. Louis International Lung Transplant
25% of patients with pulmonary hypertension evaluat- Registry failed to demonstrate survival advantage at
ed for lung transplantation in one series. 22 one and two years posttransplantation by avoiding
288 CANADIAN JOURNAL OF ANAESTHESIA

donor-recipient CMV mismatching. Positive HIV anti- or postoperative oxygenation to donor core cooling or
body or HBsAg excludes a patient as a donor. 26 Euro-Collins solution, s6
Size matching is done by comparing the predicted During harvest, a cuff of left atrium is removed
lung volumes (total lung capacity and forced vital with donor pulmonary veins to facilitate anastomosis
capacity) of the potential donor and recipient calculat- to the recipient left atrium. Ventilation is continued
ed by established formulas based on height, age and with 100% oxygen until tracheal clamping and the
sex.2s;9 Vertical and horizontal radiographic chest mea- lungs are removed en-bloc, with main bronchus and
surements of the donor and prospective recipients for pulmonary artery, and inflated to approximately ~ of
size matching may be less reliable and should not be total lung capacity. Hyperinflation of the lungs before
primary considerations for size matching.26~9Recipients harvest and during storage improves PaO 2 and early
with obstructive lung disease tolerate undersized donor posttransplantation lung function in canine experi-
lungs better than oversized donor lungs which can mental models, s7
cause pulmonary atelectasis and cardiac compression.27
Recipients with pulmonary fibrosis may receive a lung Surgical considerations
larger than the native lung because the mediastinum Postcrolateral thoracotomy is performed for SLT,
shifts and the thorax expands to accommodate the whereas bilateral antero-thoracosternotomy is per-
transplanted lung. 27,29 In patients with pulmonary formed for BSLT. Infrequently, CPB is required for
hypertension, a donor lung of comparable size to the patients undergoing SLT or BSLT except for patients
recipient is usually transplanted. 27 Undersized lungs with pulmonary hypertension. The lung with file
should be avoided in patients with septic lung disease poorer perfusion is preferentially transplanted for SLT.
because of the potential for postoperative pleural space Similarly, the less perfused lung is transplanted first
infection.26 For double lung recipients, an effort is during BSLT. Transplantation of the right lung may
made to avoid oversized donor lungs to facilitate chest be preferred for patients with COPD as unimpeded
c l o s u r e . 27 caudad movement of the hyperinflated native lung
causes less mediastinal shift and compression of the
Donor lung preparation transplanted lung. The sidedness of lung transplanta-
Viability of the ischaemic harvested lungs has been tion also depends upon surgical considerations related
extended by the use of cryopreservation methods. to the lengths of pulmonary veins and bronchi on
With optimal preservation techniques, ischaemic times each side.
up to nine hours can be tolerated without severe dete- Double lung transplant is of only historical inter-
rioration in outcome, although it has been suggested est. 12,ss,s9 Bilteral single lung transplant avoids some
that preservation time be kept under three hours, s~ of the complications of D L T . 39'4~Ischaemic complica-
Reliable pulmonary allograft function and survival tions of the airway have been reduced by adoption of
after 12-18 hr ischaemia have been achieved in sever- the bilateral main-stem bronchial anastomoses. 39
ai animal species using hypothermic perfusion with Disruption of the airway anastomosis limited success
flush solutions with or without pretreatment with of early lung transplants but newer surgical techniques
prostaglandins, s2,ss Addition of a variety of oxygen- have improved healing of the airway anastomoses,s9,41
free radical scavengers including dimethylthiourea, as Reinforcement of the end-to-end bronchial anastomosis
well as a modification of the reperfusion environment with omental wrap is no longer routinely performed for
by leukocyte depletion techniques improve lung-graft prevention of bronchial dehiscence. This procedure
function in a variety of experimental models. 34,3s aided anastomotic revasculafization by bringing an
The method of human lung preservation varies intact blood supply around the anastomosis. Instead, a
among different transplant centres. The Washington telescoping technique of intussuscepting one or two car-
University Lung Transplant Group technique involves tilaginous rings of smaller into larger bronchus is often
systemic heparinization followed by administration of employed.6,41 This technique was initially developed to
prostacyclin, 500 lag, directly into the main pul- enhance the blood supply of the bronchial anastomosis
monary artery (PA) prior to pulmonoplegia at 4~ in a canine lung transplantation model by Veith and
through a large bore cannula. 27 After gross inspection Richards, 42 and later applied clinically by the San
and palpation in situ, lungs are harvested following Antonio Lung Transplant Group. 6 In a series of 47
administration of a cold flush of Euro-Collins or patients undergoing lung transplantation, 39 underwent
University of Wisconsin solution into the PA. The end-to-end bronchial anastomosis with omentopexy,
University of Wisconsin solution in combination with and of these, six had partial or complete airway dehis-
prostacyclin donor pre-treatment may provide superi- cence. Of the remaining eight patients who underwent
Singh & Bossard: ANAESTHESIAAND LUNGTRANSPLANTATION 289

a telescoping technique with perioperative corticosteroid function, hypovolaemia, outflow tract obstruction,
administration, only one developed bronchomalacia,s9 patent foramen ovale, and direction of intracardiac
shunts besides providing additional functional and
Preoperative and intraoperative anaesthetic morphological information. 22,4s,49 Intraoperative TEE
management monitoring may avoid unnecessary institution of CPB
Anaesthetic management requires preoperative evalu- in these patients by assisting the correct diagnosis of
ation and preparation within the limited time, consid- haemodynamic dysfunction.47
erable OR resources and manpower, judicious
cardiopulmonary interventions and effective commu- Induction and maintenance of anaesthesia
nication and organization among the members of the Special considerations during induction of anaesthesia
transplant team. include the potential for regurgitation mad aspiration,
reactive airway disease, and haemodynamic instability
Preoperative preparation and monitoring secondary to poor ventricular function. After preoxy-
Preoperative considerations include airway evaluation, genation, intubation is usually performed using a modi-
NPO status, oxygen and steroid dependency, pul- fied rapid-sequence induction technique, s8,44 Either a
monary and cardiac status, and any deterioration in standard left or fight-sided double-lumen tube (DLT)
the clinical condition since the last visit. Preoperative or a combination single-lumen endotracheal tube with.
immunosuppression protocols vary: one comprises endobronchial blocker (e.g., Phycon Univent tube) is
preoperative administration of 5 mg.kgq cyclosporine used for OLV. Alternatively, a single-lumen endotracheal
po, and 2 mg.kg-1 azathioprine iv. 43 Bronchodilator tube and a bronchial blocker (Fogarty occlusion
therapy is continued until surgery and antibiotics are catheter) can be placed under direct vision with a bron-
administered iv during the immediate preoperative choscope. A left-sided DLT is prefered to a tight-sided
period. Anxiolytic or sedative premedication (e.g., tube where feasible to avoid the impaired ventilation of
midazolam iv, propranolol po, or morphine ira) may the tight upper lobe. The tight-sided DLT can also
be beneficial for patients with primary pulmonary interfere with right-sided bronchial anastomosis. During
hypertension by ameliorating any increase in PVR and BSLT, the endobronchial lumen of DLT can be retract-
RV afterload associated with anxiety. 44In patients with ed at the time of bronchial transection of the second
COPD, sedative premedication, especially with opi- lung while continuing ventilation of the first transplant-
oids, can lead to respiratory compromise by aggravat- ed lung. During use of a combination single-lumen
ing preexisting hypoxia and hypercarbia and should be endotracheal tube with an endobronchial blocker for
avoided. 44 In patients with cystic fibrosis, sedative pre- BSLT, the endobronchial blocker of the tube is with-
medication should be administered carefully to avoid drawn into the trachea after transplantation of the first
respiratory compromise. Chronically cyanotic patients lung and repositioned into the main-stem bronchus of
with severe polycythaemia may benefit from phleboto- the second lung under direct vision with a fibreoptic
my and haemodilution as prophylaxis against clotting bronchoscope, s~A nasogastric tube is inserted after intu-
derangements.4s bation of the trachea, but suction is initially avoided to
Because of the possibility of severe cardiopul- prevent removal of intragastric cyclosporine,a8
monary instability during one lung ventilation (OLV) Hypotension following induction of anaesthesia is fie-
and PA clamping, continuous PA catheter and invasive quently encountered due to tamponade secondary to
blood pressure monitoring is usually employed. The over-distension of the hmgs and impaired venous return,
PA catheter generally floats to the lung with preferen- diminished RV output as a consequence of increased
tial perfusion. During surgery, the PA catheter is pal- PVR, withdrawal of high resting catecholamines,
pated prior to PA stapling to make sure that the and/or direct cardiovascular depressant effects of anaes-
catheter is not in PA of the operative lung and, if nec- thetic drugs, ss,44 Treatment of hypotension following
essary, the PA catheter is withdrawn and refloated to induction of anaesthesia depends upon its aetiology and
the non-operative lung. The pulmonary capillary is usually directed towards maintenance of chronotropic
wedge pressure (PCWP) must be interpreted with and inotropic action of the heart, optimization of pre-
caution in association with pneumonectomy as spuri- load and afterload (including both PVR and systemic
ously low readings may be obtained. 46 Routine use of vascular resistance) and reduction of the intrathoracic
transoesophageal echocardiography (TEE) monitor- pressure. Anaesthesia is maintained using oxygen with or
ing has been recommended during lung transplanta- without air, opioids, non-depolarizing muscle relaxants,
tion. 47 Transoesophageal echocardiography can assist and benzodiazepines and/or low concentrations of
the intraoperative management by diagnosing RV dys- inhalational agents. Low concentrations of inhalational
290 CANADIAN JOURNAL OF ANAESTHESIA

agents can be used safely during maintenance of OLV SLT recipients without pulmonary hypertension who
without increasing the risk of additional intrapulmonary have early postoperative pulmonary dysfunction
shunting, sl (PaO2/FiO 2 <160). ss Nitric oxide may be the drug of
choice for treatment of pulmonary hypertension
Special intraoperative considerations and/or right ventricular failure associated with sys-
Following institution of OLV, the effects on airway temic arterial hypotension, s6
pressure, oxygenation, and haemodynamic variables are It is important to identify patients requiring CPB
assessed. Ventilation is usually performed with a volume prospectively to avoid deleterious trials of OLV or PA
cycled ventilator using tidal volumes of approx. clamping,s7 Poor RV function and pulmonary hyper-
10 ml-kg-l and inspired oxygen adjusted to maintain tension have been identified as predictors of the need
adequate arterial oxygenation. Patients with restrictive for intraoperative CPB in children, s8 Patients with
lung disease often require small tidal volumes and fast obstructive lung disease rarely require CPB compared
respiratory rate, whereas those with obstructive lung with patients with restrictive lung disease, sT,s9
disease require prolonged expiratory periods to mini- According to de Hoyas et al., the requirement for intra-
mize air trapping. Some form of differential lung venti- operative CPB can be predicted from preoperative car-
lation (continuous positive airway pressure or oxygen diopulmonary performance in SLT recipients for
instffflation to the non-ventilated lung) may at times be restrictive lung disease, s7 Although no single preopera-
necessary to minimize intrapulmonary shunting during tive predictor consistently identified patients requiring
OLV. s2 Some patients undergoing lung transplantation CPB, the combination of a six-minute walk <300 m, an
develop cardiac or respiratory instability during the pro- exercise RVEF <27%, treadmill exercise (1 mph, 4% gra-
cedure requiring CPB. Instability may be caused by dient) SaO 2 <85% with 02 supplementation, and VO 2
either inadequate ventilation or oxygenation especially >5 L.min-1 during exercise successfiflly identified
during OLV or acute RV failure following clamping of the patients requiring CPB :7 de Hoyas et al. found that
the PA artery. Cardiopulmonary instability can also preoperative cardiopulmonary performance correlated
develop due to hyperinflation of the lungs (air trapping) with intraoperative haemodynamic changes necessitat-
in patients with obstructive lung disease leading to ing CPB. s7 During trial of PA clamping, patients requir-
decreased venous return, cardiac output, and systenfic ing CPB responded with a 31% reduction ha cardiac
hypotension,sa Air trapping is not a clinical problem in index and increases in PVR and alveolar-arterial O 2 gra-
patients with pulmonary fibrosis undergoing SLT.4s dient, s7 Similarly, baseline PA pressures, PVR and alve-
Permissive hypercapnia or deliberate hypoventilafion olar-arterial Oz gradient were higher (45 • 4 mmHg,
has been employed successfully in patients with 447 __ 56 dyne.sec-cm-s and 443 + 44 mmHg, respec-
COPD. s4 Deliberate hypoventilation can ameliorate the tively) in patients with restrictive lung disease requiring
haemodynamic instability induced by air trapping and CPB. s7 H i r t e t al. noted a decrease in cardiac index
may obviate the need for CPB during lung transplanta- <1.5 L-minq and a concomitant rise in PVR from 434
tion in patients with severe obstruction to expiratory _+ 148 to 1188 • 235 dyne.sec-l-cna -s upon PA clanap-
flow. However, marked acidaenfia can become a limit- ing in patients requiring CPB during SLT for pul-
ing factor in such situations. monary fibrosis, s9 No preoperative predictors for
Right ventricular failure and hypotension can be a intraoperative CPB could be identified in adults by
considerable problem upon PA clamping. Patients Triantafillou et al. 6~ They fotmd that 61% of patients
with restrictive lung disease frequently require RV required CPB in a series of 18 patients who developed
unloading with pulmonary vasodilators as PVR often donor lung dysfunction manifested by increased PA
increases considerably on PA clamping. Prostaglandin pressure, decreased lung compliance and pulmonary
E 1 (PGEI) infusion, 4-12 ng.kg-l-min-I iv, for pul- oedema after reperfusion of the first donor lung during
monary vasodilatation leads to concomitant systemic BSLT.60
vasodilatation and arterial hypotension, and may wors- After implantation, perfusion and ventilation of the
en oxygenation due to increased intrapulmonary implanted lung are begun simultaneously. Positive end
shunting, ss,s6 Prostaglandin E l infusion during the expiratory pressure (5-10 cmH20 ) is usually added to
perioperative period may require concomitant admin- allow adequate oxygenation with a low FiO 2 and to
istration of vasopressors to maintain normotension, s6 nfinimize alveolar transudation. Frequently, a trans-
Inhaled nitric oxide (NO), 40-60 ppm, in contrast to planted lung exhibits "pulmonary reimplantation
PGE~ iv, causes selective pulmonary vasodilatation response" manifested as low pressure pulmonary oede-
without affecting systemic vasculature and mean arte- ma with poor lung compliance and oxygenation: !
rial pressuress,s6 and may also improve oxygenation in Pulmonary reimplantation response (PRR) is probably
Singh & Bossard: ANAESTHESIAAND LUNGTRANSPLANTATION 291

the result of preservation ischaemia-reperfusion lung Duration of postoperative ventilatory support report-
injury, but may also be related to denervation and loss ed by the Toronto Lung Transplant Group ranged
of lymphatic drainage of the transplanted lung. 61 from 3-10 days (mean 5.5 days) in a small series of
Shorter ischaemic times and improved donor ltmg patients undergoing SLT for pulmonary fibrosis. 9
preservation with glutathione containing solutions may
lessen the severity of the reperfusion injury. 6~,62 Pulmonary vascular disease: In patients with pul-
Administration of a prostaglandin 12 analogue monary hypertension treated with SLT, 90-95% of
(OP41483ctCD) immediately before and after reperfu- the cardiac output is diverted through the transplant-
sion can prevent the reperfusion injury by inhibition of ed lung. 6s Heavy sedation is essential during ventila-
hydoxyl (OH') free radicals generation and microem- tion for the first 48-72 hr to prevent the pulmonary
boll formation. 6s Rarely, reimplantation response may hypertensive crises. 6s
be accompanied by pulmonary hypertension. 4s
Prostaglandin E 1 infusion, 0.05 }ag.kg-Lmin-1, or BILATERAL SINGLE LUNG TRANSPLANT
inhalation of nitric oxide, 40-80 ppm, can be beneficial Prolonged ischaemia of the second transplanted lung
in these patients. 4s can increase the risk of PRR in these patients.
Mechanical ventilation in the presence of unilateral
Postoperative management lung disease (e.g., failing transplanted lung) can lead to
Optimal management of ventilation, haemodynamics hyperinflation of the contralateral lung, mediastinal
and pain; prevention and treatment of infection, and shift, and haemodynamic instability due to differences
institution of an optimal immunosuppression re#men in airway resistance or lung compliance. In such situa-
are of prime importance in the early postoperative tions, independent or differential lung ventilation with
period. or without PEEP can be employed to avoid hyperex-
pansion and barotrauma to the native Irreg. s3,66
Ventilatory management
Pulmonary reimplantation response
At the end of the surgical procedure, the double
Pulmonary reimplantation response manifests as non-
lumen tube is usually changed to a single lumen tube.
cardiogenic pulmonary oedema (PCWP ,:12 mmHg)
The goals of ventilatory management are to achieve
in the transplanted lung with hypoxaemia (requiting a
the lowest possible fraction of inspired oxygen com-
FlU 2 of 0.3 to maintain a PaO 2 >60mmHg) and alveo-
patible with adequate oxygenation and to minimize
lar and/or interstitial shadowing.61 It manifests in the
peak airway pressures.64 A combination of diuresis,
early post-transplant period (within minutes to four
PEEP, and low tidal volumes usually achieves the
days) without evidence of bacterial infection or rejec-
desired result. 64 Bronchial anastomotic damage as well
tion. 61 Clearing of the PRR is progressive, with com-
as haemodynamic embarrassment is minimized by lim-
plete resolution between the sixth and 21st day.61 The
iting the peak airway pressures to <40 cmH20.
mean duration of ventilation was seven days, ranging
Ventilatory management depends on the type of
from one to 19 days, in a series of 24 patients. 61 In con-
the transplant performed (SLT vs BSLT) and the
trast to adult respiratory distress syndrome, the prog-
underlying disease process. Five to ten mmHg of
nosis of PRR is favourable with morbidity related to
PEEP are routinely employed following SLT and
nosocomial infections and barotraunla from prolonged
BSLT except in patients with obstructive lung disease
ventilation. Fluid balance should be critically controlled
treated with SLT.
during the perioperative period as excessive fluid
SINGLE LUNG TRANSPLANT administration is believed to aggravate the clinical man-
Obstructive lun~ disease: Positive end expiratory pres- ifestations of PRR.
sure is avoided and lower tidal volumes are used to limit
overexpansion of the native lung. Preferential ventila- Ventilatory response
tion of the more compliant native lung can be treated Physiologically, the implanted denervated lung exhibits
with independent lung ventilation using a double- bronchodilatation, decreased ventilatory response to
lumen endobronchial tube. s3 In most patients with hypercapnia, and decreased pulmonary clearance and
COPD, the trachea can be extubated in three days. cough reflex. Phillipson et al. demonstrated that vagal
blockade in awake breathing dogs results in no change
Restrictive lung disease: Patients with restrictive lung in resting carbon dioxide tension. 67 Vagal sectioning
disease usually require prolonged ventilatory support results in reduced respiratory rate and higher tidal vol-
compared with patients with obstructive lung disease. umes maintaining the level of ventilatory response
292 CANADIAN JOURNAL OF ANAESTHESIA

during exercise. Increase in ventilatory response during requirement in patients requiring CPB during lung
CO 2 rebreathing after lung transplantation is principal- transplantation. 71 Blood products should be filtered
ly due to an increase in tidal volume for either single or through a 40 lam filter before administration, as the
bilateral lung transplant recipients. 6s The single lung absence of lymphatics in the transplanted lung increas-
transplant recipients, however, show an ability to es the propensity for interstitial pulmonary oedema. 3s
increase the respiratory rate in response to CO 2 In a canine model, use of uncoated, as well as heparin
rebreathing, whereas the bilateral lung transplant recip- coated, CPB had an adverse effect on arterial oxy-
ients do not. 68 In DLT recipients, the maximal ventila- genation (two hours after reperfusion), cardiac index
tion achieved during hypercapnic ventilation is less than and mean arterial blood pressure, and increased post-
the predicted maximal voluntary ventilation.69 The operative blood loss compared with the group that did
increase in PaCO 2 secondary to opioid depression not undergo CPB. 72
might be exacerbated in patients following DLT. Pulmonary hypertension and transient graft dysfunc-
Respiratory muscle weakness may also be a factor limit- tion can complicate the postoperative course following
ing ventilatory responsiveness in the face of altered pul- lung transplantation. It has been demonstrated in a
monary mechanics or function, i.e., restriction, canine model that the use of CPB during lung trans-
obstruction, or a mixed pattern. 69Frost et al. could not plantation greatly exaggerates pulmonary vasomotor
identify any other contributing cause for the dispropor- dysfunction in the transplanted lung due to much
tionate blunting of the hypercapnic ventilatory response greater impairment of both endothelium-dependent
to the degree of pulmonary dysfunction. 69 Comparison cyclic guanosine monophosphate and lg adrenergic cyclic
of the hypercapnic ventilatory responses of transplant adenosine monophosphate-mediated relaxation. This
patients with similarly obstructed or restricted control dysfimction may contribute to considerably higher pul-
subjects would further clarify the contribution of pul- monary vascular resistance in the transplanted lung.73
monary mechanics vs pulmonary denervation in the Nitric oxide administration, 10-80 ppm, can improve
control of breathing. 69 oxygenation and decrease pulmonary artery pressures
without adverse haemodynamic effect; however, tran-
Haemodynamic and fluid management sient methaemoglobinaemia can develop secondary to
For haemodynanfic stabifit3; optimization of preload prolonged treatment.74 Administration of prostaglandin
aaad afterload is essential. Development of a reimplanta- E 1 also improves early graft function (oxygenation) in
tion response manifesting as low pressure pulmonary mongrel dogs following lung transplantation. 7s
oedema secondary to microvascular leak is common in
the early postoperative period. 6I There is, however, Pain management
concern regarding the amount of crystaUoid that can Patients undergoing thoracotomy experience severe
safely be adnainistered without adversely affecting graft respiratory impairment postoperatively secondary to
function. 61 According to Karanikolas et al. the amount severe pain. The provision of postoperative analgesia is
of fluid administered to maintain haemodynanfic stabil- complicated by pulmonary denervation, wide thoraco-
ity dtu'ing lung transplantation did not adversely affect tomy incision, and residual pulmonary impairment.
the graft function (PaOz/FiO2) or time to extuba- Epidural, compared with iv opioid analgesia, decreases
tion. 7~ To augment urine output, loop diuretics are the time to extubation and intensive care unit stay of
usually administered in the early postoperative period. 64 these patients. 76 An epidural catheter can safely be
Postoperative haemorrhage is more common in placed preoperatively in these patients while the coagu-
patients requiring CPB during transplantation. 64 lation status is normal. 77 Thomas and Siegel reported
Cardiopulmonary bypass is associated with increased excellent postoperative analgesia and earlier extubation
blood transfusion requirement, longer postoperative (13-hr postoperatively) in a SLT recipient administered
ventilation, and longer hospital stay in patients under- a bolus ofepidural hydromorphone, 1.5 mg (in 10 ml
going DLT for cystic fibrosis. 4~ In another study, use preservative free saline), followed by an epidural infu-
of CPB was associated with considerably increased sion at 0.25.mg.hr-1.7s Body et al. reported postopera-
transfusion of packed erythrocytes, platelets, and cry- tive hypercapnia associated with epidural analgesia in a
oprecipitate, s4 However, according to Triantafillou series of 29 patients undergoing SLT or BSLT. These
et al. use of CPB did not adversely affect the outcome patients received an epidural infusion of bupivacaine
expressed in terms of time to extubation, duration of 0.125-0.25% (mean rate: 5.2-8.3 ml.hr-1) with either
ICU stay, and the time required to reach a room air fentanyl 5 lag.m1-1 or meperidine 2.5 mg.ml-l. 79
PaO 2 >60 mmHg. 6~ Administration of aprotinin Hypercapnia could have been due to the central action
decreases postoperative blood loss and blood product of epidural opioids, or to a failure to reset brainstem or
Singh & Bossard: ANAESTHESIAAND LUNG TRANSPLANTATION 293

peripheral chemoreceptors, or due to underlying mech- Trough blood concentrations are obtahaed one hour
anisms described previously. 67-69 before the oral dose to adjust the dosing schedule to
maintain a therapeutic level of 400-500 ng.ml -l, based
Antimicrobials and immunosuppression on radioimmunoassay, or 250-300 ng.ml -l using a high-
Both donor and recipients are subjected to bron- pressure liquid chromatography assay,s~ Azathioprine,
choscopy preoperatively. Antibiotic coverage, based on 1.5 mg-kg-I iv, is administered as a single daily dose dur-
Gram- stain and culture results from the donor ing the first week, and thereafter it is administered po.
bronchial washings, has decreased the incidence and White blood cell count is monitored to adjust the dose
severity of bacterial infection. 8~ Cephalosporins are ofazathioprine, with decreased dose for white blood cell
usually administered during the first 24 48 hr postoper- count <6000.mm-L s~ Effects of a new immtmosuppres-
atively and are discontinued if there are no symptoms or sant drug, FK 506, have recently been compared with
signs of pneumonitis or sepsis. Investigation of any cyclosporine in both paediatfic mad adult patients, sr,ss
unexplained fever or pulmonary infiltrates should be Results are encouraging in children and in preliminary
supplemented with bronchoscopy, bronchoalveolar randomized trials in adults. Use of FK 506 reduced the
lavage and protected brush specimens with quantitative incidence of acute rejection and improved dae interme-
cultures. 64,sl Third or fourth generation cephalosporins diate graft survival at six months as compared to the
are preferred to aminoglycosides to avoid aminoglyco- cyclosporine-treated group in the adult population, ss
side-related nephrotoxicity. These patients also receive Cyclosporine-induced nephrotoxicity occurs in
trimethoprim and sulfamethoxazole for prevention of 25-75% of the recipients and is usually dose related mad
Pneumocystis carinii, s2 Ganciclovir alone or in combina- reversible, s9 Other drugs used during the peritransplant
tion with CMV hyperimmune globulin is administered period such as amphotericin B, furosemide, aminoglyco-
for prevention of CMV if either the donor or recipient sides, and trimethoprim/stdfamethoxazole appear to
has a CMV-seropositive test result before surgery, s,sl,s3 increase the cyclosporine toxicity. 9~ Cyelosporine-
The prophylactic use of ganciclovir has reduced the induced hypertension, a defect of sodium excretion,
prevalence of CMV infection from 71% to 16%.8 occurs in approximately 25-50% of patients, s'9~
Commonly used maintenance immunosuppression pro-
tocols involve administration of prednisone, azathio- Delayed complications after lung transplantation
prine and cyclospotine,s Induction protocols may vary Posttransplant patients receive immuosuppression
between centres as early use of corticosteroids for therapy for life and are at increased risk of infection.
immunosuppression after transplantation was thought Early recognition, differentiation of infection from
to affect airway heating adversely. Methylprednisolone, rejection, and prompt initiation of therapy are of crit-
500 nag iv, is usually administered just before revascu- ical importance.
larization of the implanted lung followed by a mainte-
nance dose of 0.5-4 mg.kg--lday-1 for three to four Infection
days. 6,s9 Thereafter, prednisone 0.5 mg-kg--lday-l po, is Bacteria are the most likely organisms to cause infection
instituted and gradually tapered to a low maintenance during the early posttransplantation period, whereas
dose. Alternatively, T-cell lytic therapy can be employed opportunistic pathogens such as CMV are the frequent
for induction immunosuppression. Routinely used cause of infection later as the T-cell mediated immunity
preparations include ATGAM, a polyclonal antithymo- wanes over weeks following immunosuppression, s.l
cyte globulin, and OKT-3, a Murine monoclonal anti- Infection usually arises within the allograft (80%) and
body (antibody to T3 antigen of hunaan T cells). Acute accounts for the majority of the complications, s Gram
adverse effects ofT-cell lytic therapy include fever, dysp- negative bacterial pneumonias are the most common
noea, pulmonary oedema, hyperglycaemia, hypotension, postoperative infections and are associated with a lower
myalgia-arthralgia syndrome and malaise, s4,ss Besides mortality. 8 Infectious complications with pan-resistant
acute adverse effects, there is an increased incidence of (resistant to most antibiotics) Pseudomonal species or
lymphoproliferative disorders and CMV infections, ss,s6 Pseudomonas cepacia are associated with a higher mor-
T-cell lytic therapy is adjusted by monitoring the tality and earlier and more frequent development of
absolute number of peripheral T-cell subset (CD-3 T obliterative bronchiolitis (OB) in survivors, s9 Vir,~ and
lymphocytes) by flow cytometry and by observing the fungal (e.g., CMV, Epstein Barr Virus, Candida,
adverse clinical effects of therapy, s4,ss Cyclosporine iv is Cryptococcus and Aspergillus) infections are associated
administered during first two to three days at an initial with a higher mortality, s
dose of 100-150 mg.24.hr -1. Cyclosporine iv is tapered Cytomegalovirus infection varies in severity from
when therapeutic levels are achieved with oral dosing. asymptomatic shedding of the virus to CMV syndrome
294 CANADIAN JOURNAL OF ANAESTHESIA

and pneumonitis. One series reported 87% and 71% ment with more effective immunosuppressants, and a
prevalence of CMV infection, if either the donor or better understanding of basic pathophysiology of the
recipient was seropositive for CMV, respectively,s In allogenic process.
contrast, CMV infection develops in <10% of seronega-
tive patients receiving lung allografts from a seronegative Causes of death
donor. Infection in the seronegative recipients is more Infection is the most common cause of early death
likely to be symptomatic (95% vs 45%) and fatal (45% vs (<90 days posttransplant), whereas primary organ fail-
10%) than in the seropositive recipients, s By using mul- ure manifesting as diffuse alveolar damage/adult res-
tivariate analysis, Bando et al. demonstrated that CMV piratory distress syndrome is the most common
mismatch, absence of CMV prophylaxis, and develop- complication and the second most common cause of
ment of CMV disease are severe threats for death, rejec- early death (Table I I I ) . 1's9'91 Chronic rejection in the
tion, and infection after pulmonary transplantation. 91 form of OB and infection (excluding CMV) are fre-
Prevention of CMV disease improves survival by quent causes of delayed morbidity and mortality (90
decreasing the prevalence of infection and rejection.91 days posttransplant) following lung transplantation
(Table IV). 1,39,91
Acute rejection
Acute rejection episodes can be either asymptomatic or Anaesthesia in patients with lung transplant
present with fever, shortness of breath, generalized Lung transplant patients may require anaesthesia for
fatigue, and hypoxaemia. Surveillance includes frequent follow up procedures (e.g., assessment of airway heal-
chest-X rays, ABG analysis, pulmonary function tests ing, transbronchial biopsy), surgical exploration for
(10% decrease in FVC and FEV 1 is considered signifi- infectious complications or bleeding, retransplanta-
cant),92 and transbronchial lung biopsy.93 Sensitivity and tion, or unrelated surgical procedures. Defects in air-
specificity of the transbronchial biopsy for diagnosing way healing leading to bronchial stenosis or airway
acute rejection has been reported to be 84% and 100%, dehiscence are frequent complications requiring place-
respectively.93 ment of airway stents or reanastomosis. During pre-
Given the short and long term adverse effects of operative evaluation, special emphasis is placed on
rejection, aggressive therapy following positive trans- function of the transplanted lung, presence or absence
bronchial biopsy is critical. Dramatic clinical response
with improvement in gas exchange, spirometry, and
radiographic appearance to a pulse dose of methyl- TABLE 3 Causes of Early Transplant Recipient Deaths l
prednisolone, 500-1000 mg iv, is considered to con- Cause of death %/n (Total) *
firm the diagnosis of acute rejection, s9 Treatment of
acute rejection includes a three day course of high Infection (Other than CMV) 29%
Primary Organ Failure 13%
dose boluses of methylprednisolone iv followed by Cardiac Failure 9%
oral prednisone. OKT3 therapy can be employed for Haemorthage 6%
steroid resistant, high grade, or relapsing acute lung Multi-organ Failure 6%
Airway Dehiscence 5%
rejection during the first six months, ss Rejection 5%
CMV 5%
Obliterative bronchiolitis Other 22%
Obliterative bronchiolitis is defined clinically by an *Values are percentage of total number (n=848)
obstructive pulmonary function defect and histological-
ly by obliteration of the terminal bronchioles and is the
main long term complication following lung transplan- TABLE 4 Causes of Delayed Transplant Recipient Deaths t
tation. The incidence of OB has been reduced with Cause of death %/n (Total) *
augmented immunosuppression, and progression of the Bronchiolitis Obliterans/Rejection 29%
disease has also been slowed.94 The origin of OB Infection (Other than CMV) 24%
remains unclear, however, it is believed to be a manifes- Malignancy 6%
tation of chronic allograft rejection.94 Chronic rejection CMV 5%
Respiratory Failure 5%
is defined by histologic evidence of OB in the absence Haemorrhage 4%
of infection, and is associated with dyspnoea, cough, Multi-Organ Failure 3%
and a progressive restrictive and obstructive defect of Cardiac Failure 2%
Other 21%
the small airways.94 Improved management of chronic
rejection will require closer surveillance, earlier treat- *Values are percentage of total number (n~932)
Singh & Bossard: ANAESTHESIAAND LUNG TRANSPLANTATION 295

of infection and/or rejection, and side effects and 100


interactions ofimmunosuppressive therapy. In patients .-~- EMP (n=2OlS)
--41-CF (n=738)
receiving steroids, administration of a perioperative 90
9m PF (n=804]
dose of steroids is common, although controversial. B9 (n=506]
Appropriate antibiotic prophylaxis is administered in
the immediate preoperative period. All peripheral, ~_ 7 0
central and arterial cannulae should be inserted under .~ 60
full aseptic techniques and intravenous infusion ports ~ 50
should be capped and kept sterile. Fluids should be
administered judiciously as the transplanted lung is 40
devoid of lymphatic drainage. Concerns about altered 30
lung physiology (i.e., denervation) have been found to 20 I I I I I
be of theoretical rather than practical significance. 44 1 2 3 4 5
Peak airway pressures should be minimized during Posttransplant (Yr)
IPPV to avoid damage to the bronchial anastomosis.
FIGURE 1 FiveYearActuarial Survivalby Diagnosis(From the
High frequency jet ventilation via transbronchial St. Louis International Lung)
catheter has been used in the management of airway Transplant RegistryData); EMP (emphysaema),CF (cysticfibrosis),
complications following lung transplantation. 9s PF (pulmonaryfibrosis),PPH (primarypulmonary hypertension)
Patient survival and future directions
Survival after lung transplantation has improved pro-
gressively during the last decade. According to the St.
100, BSLT (n=1771)
Lotfis International Lung Transplant Registry data,
actuarial survival following lung transplantation is 71% 90
(one-year), 63% (two-year), 56% (three-year), 50% 80
(four-year), 45% (five-year), 39% (six-year) and 34%
.~ 7 0
(seven-year). Currently, one year survival for patients
undergoing BSLT/SLT approaches 80-90% in some >~ 60
P
centres. Survival in the paediatric age group is 66% u~ 5 0
(one-year), 57% (two-year) and 48% (three-year). 1 40.
Results are better for patients with emphysema than
30
for those with cystic fibrosis, pulmonary hypertension,
and pulmonary fibrosis (Figure 1). Patients undergo- 2O I I I I I
1 2 3 4 5
ing BSLT do better than those undergoing SLT
Post~ransplant(Yr)
(Figure 2). This may be related to a better tolerance of
chronic graft dysfunction in patients with bilateral FIGURE 2 FiveYearActuarial Survivalby Transplant Type
lung replacement. Survival for patients undergoing (From the St. Louis International
retransplant is 49% (one-year), 42% (two-year) and Lung Transplant RegistryData); SLT (shagle-lungtranspl,'mt),
37% (three-year). 1 BSLT(bilateralsingle-lungtransplant), DLT (En-blocdouble-lung
Pulmonary function improves markedly following transplant).
lung transplantation. 96 The FEVI, FVC and M W
(maximum ventilatory volume) are increased in all
recipients except in patients with pulmonary hyper- al volume reduction surgery (excision of 20-30% of
tension. The PaO 2 also improves, and oxygen depen- the volume of each lung) in patients with severe
dent patients are able to function without oxygen COPD, Cooper et al. reported an improvement in
therapy. 97 Despite improvement, these patients still FEV l by 82% and considerable reduction in total hmg
have severe exercise limitation following lung trans- volume, residual volume and trapped gas. 9s These
plantation. Maximum work rates and VO 2 max are changes have been associated with marked relief of
approximately half that of predicted and the anaerobic dyspnoea and improvement in exercise tolerance and
threshold is also reduced. 96 This persistent abnormal- quality of life. This procedure may serve as a possible
ity in exercise capacity has been attributed to chronic alternative to lung transplantation for a select group of
muscle deconditioning with accompanying abnormal patients, or may act as a bridge to transplantation at a
cardiovascular response to exercise. Following bilater- later date when subsequent deterioration occurs.
296 CANADIAN JOURNAL OF ANAESTHESIA

Delayed complications of chronic rejection/OB 5 Toronto Lung Transplant Group. Unilateral lung
and infection have become the most important chal- transplantation for pulmonary fibrosis. N Engl J Med
lenges limiting the benefit of lung transplantation. 1986; 314: 1140-5.
The improved long term outlook will depend to a 6 CalhoonJH, Grover FL, Gibbons WJ, et al. Single lung
large extent on better treatment of OB and infection. transplantation. Alternative indications and technique.
Other issues including shortage of donor organs, J Thorac Cardiovasc Surg 1991; 101: 816-24.
short preservation times, and financial costs to the 7 Ritchie M, WaggonerAD, D~vila-Rom~n VG, Barzilai
healthcare system remain to be fully addressed. B, Trulock EP, EisenbergPR. Echocardiographic char-
Current areas of active research include prolongation acterization of the improvement in right ventricular
of preservatlon-ischaemic times, prevention of reper- function in padents with severe pulmonary hyperten-
fusion injury, and feasibility of pulmonary xenotrans- sion after single-lung transplantation. J Am Coll
plantation. 99 Xenotransplantation holds the promise Cardiol 1993; 22: 1170-4.
of an abundant supply of donor organs; however, con- 8 Griffith BP, Hardesty RL, ArmitageJM~ et al. A
siderable advances in this area will be required before decade of lung transplantation. Ann Surg 1993; 218:
this procedure becomes a reality. Average cost per 310-20.
lung transplantation is estimated to be US$164,989 9 The Toronto Lung Transplant Group. Experience with
followed by post-transplant maintenance charges of single-lung transplantation for pulmonary fibrosis.
$11,917/mo (first-year) and $4,525 thereafter. I~176 JAMA 1988; 259: 2258-62.
Expenses incurred by patients on waiting list are esti- 10 Bando K, Keenan RJ, Paradis IIo et al. Impact of
mated to be $3,395/mo. 1~176 pulmonary hypertension on outcome after single-
lung transplantation. Ann Thorac Surg 1994; 58:
1336--42.
Sunanaary 11 Shennib H, Massard G, Gauthier R, Colman N,
Lung transplantation offers hope of improved quality Mulder D. Single lung transplantation for cystic fibro-
of life in patients with end stage lung disease. The sis: is it an option? J Heart Lung Transplant 1993;
major limitation of the procedure relates to the high- 12: 288-93.
er costs with marginal improvement in life expectancy 12 CooperJD, Patterson GA, Grossman R, Maurer J,
compared with conservative treatment (5.89 yr vs Toronto Lung Transplant Group. Double-lung trans-
5.32 yr). 1~176
In summary, although the future of lung plant for advanced chronic obstructive lung disease.
transplantation seems promising with potential for Am Rev Respir Dis 1989; 139: 303-7.
rapid growth, its economic impact on the healthcare 13 Morrison DL, Maurer JR, Grossman RF. Preoperative
system will continue to draw attention. assessment for lung transplantation. Clin Chest Med
1990; 11: 207-26.
Acknowledgments 14 WatersPF. Lung transplantation: recipient selection.
The authors express their appreciation to Dan M. Semin Thorac Cardiovasc Surg 1992; 4: 73-8.
Meyer, MD for his suggestions regarding surgical 15 GoldbergM, Lima O, Morgan E, et al. A comparison
management of these patients. The assistance of Mary between cyclosporin A and methylprednisolone plus
Pohl, RN is acknowledged for assisting with the St. azathioprine on bronchial healing following canine
Louis International Lung Transplant Registry data. lung autotransplantation. J Thorac Cardiovasc Surg
1983; 85: 821-6.
16 SchSfersH-J, Wagner TOF, Demertzis S, et al.
References Preoperative corticosteroids. A contraindication to
1 CooperJD, Pohl MS. Report of the St. Louis lung transplantation? Chest 1992; 102: 1522-5.
International Lung Transplant Registry, Washington 17 Massard G, Shennib H, Metras D, et al. Double-lung
University School of Medicine, April 1996. transplantation in mechanically ventilated patients with
2 United Network for Organ Sharing Scientific Registry cystic fibrosis. Ann Thorac Surg 1993; 55: 1087-92.
Data, 1995. 18 Flume PA, Egan TM, Westerman JH, et al. Lung
3 HardyJD, Webb WR, Dalton MLJr, Walker GR. transplantation for mechanically ventilated patients. J
Lung homotransplantation in man. JAMA 1963; 186: Heart Lung Transplant 1994; 13: 15-21.
1065-74. 19 Jurmann MJ, Schaefers H-J, Demertzis S, Haverich A,
4 VeithFJ, Kamholz SL, MollenkopfFP, Montefusco CM. Wahlers T, Borst HG. Emergency lung transplantation
Lung transplantation 1983. Transplantation 1983; after extracorporeal membrane oxygenation. ASAIO J
35: 271-8. 1993; 39: M448-52.
$ingh & Bossard: ANAESTHESIAAND LUNG TRANSPLANTATION 297

20 Leibowitz DW,, Caputo AL, Shapiro GC, et al. 34 Lambert CJJr, Egan TM. Optimal timing of adminis-
Coronary angiography in smokers undergoing evalua- tration of a free radical scavenger in lung preserva-
tion for lung transplantation: is routine use justified? tion. Transplantation 1992; 54: 205-9.
J Heart Lung Transplant 1994; 13: 701-3. 35 SchuelerS, De Valeria PA, Hatanaka M, et al.
21 Vigne~varan WT, McDougallJC, Olson LC, BreenJF, Successful twenty-four-hour lung preservation with
McGregor CGA, Rumberger JA. Right ventricular donor core cooling and leukocyte depletion in an
assessment in patients presenting for lung transplanta- orthotopic double lung transplantation model. J
tion. Transplantation 1993; 55: 1051-5. Thorac Cardiovasc Surg 1992; 104: 73-82.
22 GorscanJIII, Edwards TD, Ziady GM, Katz WE, 36 Hirt SW, Wahlers T, Jurmann M, Fieguth HG,
Griffith BP. Transesophageal echocardiography to Dammenhayn L, Haverich A. Improvement of cur-
evaluate patients with severe pulmonary hypertension rently used methods for lung preservation with
for lung transplantation. Ann Thorac Surg 1995; 59: prostacyclin and University of Wisconsin solution. J
717-22. Heart Lung Transplant 1992; 11: 656-64.
23 Winton TL, Miller JD, Seavuzzo M, Maurer JR, 37 PuskasJD, Hirai T, Christie N, Mayer E, Slutsky AS,
Patterson GA, TorontoLung Transplant Group. Patterson GA. Reliable thirty-hour lung preservation
Donor selection for pulmonary transplantation. by donor hmg hyperinflation. J Thorac Cardiovasc
Transplant Proc 1991; 23: 2472-4. Surg 1992; 104: 1075-83.
24 Haydock DA~ Low DE, Trulock EP, et al. Pulmonary 38 GayesJM, Giron I o Nissen MD, Hut D. Anesthetic con-
"twinning" procedure: use of lungs from one donor siderations for patients undergoing double-lung trans-
for single-hing transplantation in two recipients. Ann plantation. J"Cardiothorac Anesth 1990; 4: 486-98.
Thorac Surg 1992; 54: 1189-92. 39 de HoyosAL, Patterson GA, Maurer JR, et al.
25 Starnes VA, Barr MI~ Cohen RG. Lobar transplanta- Pulmonary transplantation. Early and late results. J
tion. Indications, technique, and outcome. J Thorac Thorac Cardiovasc Surg 1992; 103: 295-306.
Cardiovasc Surg 1994; 108: 403-10. 40 Egan TM, Detterbeck FC, Mill MR, et al. Improved
26 Winton T. Lung transplantation: donor selection. results of lung transplantation for patients with cystic
Semin Thorac Cardiovasc Surg 1992; 4: 79-82. fibrosis. J Thorac Cardiovasc Surg 1995; 109:
27 Sundaresan S, Trachiotis GD, Aoe M, Patterson GA, 224-35.
CooperJD. Donor lung procurement: assessment and 41 RamirezJ, Patterson GA. Airway complications after
operative technique. Ann Thorac Surg 1993; 56: lung transplantation. Semin Thorac Cardiovasc Surg
1409-13. 1992; 4: 147-53.
28 Shumway SJ, Hertz MI, Petty MG, Bolman RM IIL 42 Veith FJ, Richards If. Improved technic for canine
Liberalization of donor criteria in lung and heart-lung lung transplantation. Ann Surg 1970; 171: 553-8.
transplantation. Ann Thorac Surg 1994; 57: 92-5. 43 CooperJD, Patterson GA. Lung transplantation. In:
29 Egan TM, Kaiser LR, CooperJD. Lung transplanta- WaUwork J (Ed.). Heart and Heart-Ltmg Trvalspl,'m-
tion. Curr Probl Surg 1989; 26: 728-34. tation. Philadelphia, PA: W P Saunders, 1989: 501.
30 SchafersHJ, CooperJD. Lung transplantation for pul- 44 Triantafillou AN, Heerdt PM. Lung transplantation.
monary disease in cardiac surgery. In: Emery RW Int Anesthesiol Clin 1991; 29: 87-109.
(Ed.). Cardiothoracic Transplantation. Philadelphia, 45 FehrDM, Aufiero TX, Firestone Io Firestone S.
PA: Hanley and Belfus, 1988: 582. Anesthetic management for surgery of the lungs and
31 Winton TL, Miller JD, de HoyosA, Snell G, Maurer J. mediatinum. In: Hensley FA Jr, Martin DE (Eds.). A
Graft function, airway healing, rejection, and survival Practical Approach to Cardiac Anesthesia. Boston:
in pulmonary transplantation are not affected by graft Little, Brown and Company, 1995: 652-6.
ischemia in excess of 5 hours. Transplant Proc 1993; 46 Wittnich C, TrudelJ, Zidulka A, Chiu RC-J.
25: 1649-50. Misleading "pulmonary wedge pressure" after pneu-
32 Novick RJ, Reid KR, Denning L, Duplan J, Menkis monectomy: its importance in postoperative fluid
AH, McKenzie FN. Prolonged preservation of canine therapy. Ann Thorac Surg 1986; 42: 192-6.
lung allografts: the role of prostaglandins. Ann 47 Brown MJ, Licina MG, Savage RM, Kraenzler E,[,
Thorac Surg 1991; 51: 853-9. Hearn C, Kirby TJ. Transesophageal echoc,ardiogra-
33 Mayer E, PuskasJD, CardosoPFG, Shi S, SlutskyAS, phy should be used during anesthesia for hmg trans-
Patterson GA. Reliable eighteen-hour lung preserva- plantation. Anesthesiology 1994; 81: A547.
tion at 4 ~ and 10~ by pulmonary artery flush after 48 Conacher ID, McNally B, Choudhry AK, McGregor
high-dose prostaglandin E 1 administration. J Thorac CGA. Anaesthesia for isolated lung transplantation.
Cardiovasc Surg 1992; 103: 1136--42. Br J Anaesth 1988; 60: 588-91.
298 CANADIAN JOURNAL OF ANAESTHESIA

49 GorscanJ III, Reddy SCB, Armitage JM, Griffith BP. 62 Bryan CL, Patefidd AJ, Cohen D, Nielsen JL,
Acquired right ventricular outflow tract obstruction Emanuel B, CalhoonJH. Assessment of injury in
after lung transplantation: diagnosis by transesophageal transplanted and nontransplanted lungs after 6 h of
echocardiography. J Am Soc Echocardiogr 1993; 6: cold storage with glutathione. J Appl Physiol 1994;
324-6. 76: 1232--41.
50 SchellerMS, Kriett JM, Smith CM, Jamieson SW. 63 Takeuchi K, Suzuki S, Kako N, et al. A prostacyclin
Airway management during anesthesia for double- analogue reduces free radical generation in heartqung
lung transplantation using a single-lumen endotra- transplantation Ann Thorac Surg 1992; 54: 327-32.
cheal tube with an enclosed bronchial blocker. J 64 Todd TRJ. Early postoperative management following
Cardiovasc Thorac Anesth 1992; 6: 204-7. lung transplantation. Clin Chest Med 1990; 11:
51 BenumofJL. One-lung ventilation and hypoxic pul- 259-67.
monary vasoconstriction: implications for anesthetic 65 PasqueMK, Kaiser LR, Dresler CM, Trulo& E,
management. Anesth Analg 1985; 64: 821-33. Triantafillou AN, CooperJD. Single lung transplanta-
52 Capan LM, Turndorf H, Patel C, Ramanathan S, tion for pulmonary hypertension. Technical aspects
Acinapura A, Chalon J. Optimization of arterial oxy- and immediate hemodynamic results. J Thorac
genation during one-lung anesthesia. Anesth Analg Cardiovasc Surg 1992; 103: 475-82.
1980; 59: 847-51. 66 Gavazzeni V, Iapichino G, Mascheroni De et al.
53 SmileyRM, Navedo AT, Kirby T, Schulman LL. Prolonged independent lung respiratory treatment
Postoperative independent lung ventilation in a single- after single lung transplantation in pulmonary emphy-
lung transplant recipient. Anesthesiology 1991; 74: sema. Chest 1993; 103: 96-100.
1144 8. 67 PhillipsonEA, Hickey RF, Bainton CR, Nadel JA.
54 Quinlan JJ, Buffington CW. Deliberate hypoventila- Effect of vagal blockade on regulation of breathing in
tion in a patient with air trapping during lung trans- conscious dogs. J Appl Physiol 1970; 29: 475-9.
plantation. Anesthesiology 1993; 78: 1177-81. 68 TrachiotisGD, Knight SR, Pohl MS, Patterson GA,
55 Triantafillou AN, Pohl MS, Okayabashi K, CooperJD, CooperJD, Trulock EP. Tidal volume and respiratory
Patterson GA, Lappas DG. Effects of inhaled nitric rate changes during CO 2 rebreathing after lung trans-
oxide and prostaglandin E 1on hemodynamics and plantation. Ann Thorac Surg 1994; 58: 1718-20.
arterial oxygenation in patients following single lung 69 FrostAE, Zamel N, McClean P, GrossmanR,
transplantation. Anesth Analg 1995; 80: SCA40. Patterson GA, Maurer JR. Hypercapnic ventilatory
56 Rajek MA, Hiesmayr M, Heilinger D, Mares P, response in recipients of double-lung transplants, fian
KastnerJ, Haider 14I.Controlled trial on prevention Rev Respir Dis 1992; 146: 1610-2.
of acute right heart failure after heart transplantation 70 Karanikolas MS, Triantafillau AN, Pond CG, et al.
with nitric oxide inhalation or prostaglandin infusion. Outcome of lung transplantation in relation to intra-
Anesth Analg 1995; 80: SCA101. operative crystalloid fluid administration.
57 de HoyosA, Demajo W, Snell G, et al. Preoperative Anesthesiology 1994; 81: A1464.
prediction for the use of cardiopulmonary bypass in 71 Kesten S, de HoyasA, Chaparro C, WestneyG, Winton T,
the lung transplantation. } Thorac Cardiovasc Surg MaurerJR. Aprotinin reduces blood loss m lua~gtrans-
1993; 106: 787-95. plant recipients. Aim Thorac Surg 1995; 59: 877-9.
58 FirestoneS, Carrera J, Firestone L. Pediatric double 72 Francalancia NA, Aeba R, Yousem SA, Griffith BP,
lung transplantation: who needs bypass? Marrone GC. Deleterious effects of cardiopulmonary
Anesthesiology 1994; 81: A1389. bypass on early graft function after single lung allo-
59 Hirt SW, Haverich A, WahlersT, Sch~fersH-J, Alken transplantation: evaluation of a heparin-coated bypass
A, Borst H-G. Predictive criteria for the need of extra- circuit. J Heart Lung Transplant 1994; 13: 498-507.
corporeal circulation in single-lung transplantation. 73 Fullerton DA, McIntyre RC ]r, Mitchell MB,
Ann Thorac Surg 1992; 54: 76--80. Campbell DN, Grover FL. Lung transplantation with
60 Triantafillou AN, Pasque MK, Huddleston CB, et al. cardiopulmonary bypass exaggerates pulmonary vaso-
Predictors, frequency, and indications for cardiopui- motor dysfunction in the transplanted lung. ] Thorac
monary bypass during lung transplantation in adults. Cardiovasc Surg 1995; 109: 212-7.
Aim Thorac Surg 1994; 57: 1248-51. 74 Adatia I, Lillehei C, Arnold JH, et al. Inhaled nitric
61 Sleiman Ch, Mal H, Fournier Met al. Pulmonary oxide in the treatment of postoperative graft dysfunc-
reimplantation response in singlequng transplanta- tion after lung transplantation. Ann Thorac Surg
tion. Eur Resp ] 1995; 8: 5-9. 1994; 57: 1311-8.
Singh & Bossard: ANAESTHESIAAND LUNG TRANSPLANTATION 299

75 Aoe 3/1, Trachiotis GD, Okayabashi K, et al. after human pulmonary transplantation.
Administration of prostaglandin E 1 after lung trans- Transplantation 1994; 57: 848-51.
plantation improves early graft function. Ann Thorac 89 Vine W, Bowers LD. Cyclosporine: structure, pharma-
Surg 1994; 58: 655-61. cokinetics, and therapeutic drug monitoring. Crit Kev
76 Triantafillou AN, Heerdt PM, Hogue CW, et al. Clin Lab Sci 1987; 25: 275-311.
Epidural vs intravenous morphine for postoperative 90 Kahan BD. Cyclosporine. N Engl J Med 1989; 321:
pain management after lung transplantation. 1725-38.
Aaaesthesiology 1992; 77: A858. 91 Bando K, Paradis IL, Komatsu K, et al. Analysis of
77 Karanikolas MS, Triantafillou AN, Pond CG, et aL time-dependent risks for infection, rejection, and
Epidural catheter placement in lung transplantation. death after pulmonary transplantation. J Thorac
Before or after the operation? Anesth Analg 1995; Cardiovasc Surg 1995; 109: 49-59.
80: SCA30. 92 Otulana BA, Higenbottam T, Ferrari L, Scot,J,
78 ThomasBJ, Siegel LC. Anesthetic and postoperative Igboaka G, WallworkJ. The use of home spirometry in
management of single-lung transplantation. J detecting acute lung rejection and infection following
Cardiothorac Vasc Anesth 1991; 5: 266-7. heart-lung transplantation. Chest 1990; 97: 353-7.
79 Body S, Fanciullo G, Ferrante M, Reilly J, Sugarbaker 93 Higenbottam T, Stewart S, Penketh A, WallworkJ.
D, Mentzer S. Thoracic epidural analgesia after lung Transbronchial lung biopsy for the diagnosis of rejec-
transplantation. Anesthesiology 1994; 81: A1285. tion in heart-lung transplant patients. Transplantation
80 Davis RD Jr, Pasque MK. Pulmonary transplantation. 1988; 46: 532-9.
Ann Surg 1995; 221: 14-28. 94 TheodoreJ, Starnes VA, Lewiston NJ. Obliterative
bronchiolitis. Clin Chest Med 1990; 11: 309-21.
81 Dauber JH, Paradis IL, Dummer JS. Infectious com-
plications in pulmonary allograft recipients. Clin 95 PanosL, Patterson GA, Demajo WA. The use of high-
Chest Med 1990; 11: 291-308. frequency jet ventilation during post-lung transplan-
tation surgery. J Cardiothorac Vasc Anesth 1993; 7:
82 Kramer MR, Stoehr C, Lewiston NJ, Starnes VA,
202-3.
Theodorej[. Trimethoprim-sulfamethoxazole prophy-
96 Williams TJ, Patterson GA, McClean P, Zamel N,
laxis for pneumocystis carinii infections in heart-lung
MaurerJR. Maximal exercise testing in single and
and lung transplantation - how effective and for how
double lung transplant recipients. Am Rev Respir Dis
long? Transplantation 1992; 53: 586-9.
1992; 145: 101-5.
83 Zamora MR s Fullerton DA, Campbell DN, et al. Use of
97 Williams TJ, Grossman RF, Maurer JR. Long-term
cytomegalovirus (CMV) hyperimmune globulin for
functional follow up of lung transplant recipients.
prevention of CMV disease in CMV-seropositive lung
Clin Chest Med 1990; 11: 347-58.
transplant recipients. Transplant Proc 1994; 26: 49-51.
98 CooperJD, Trulock EP, Triantafillou AN, et al.
84 Abouna GM, Al-Abdullah IH, Kelly-Sullivan D, et al.
Bilateral Pneumonectomy (volume reduction) for
Randomized clinical trial of antithymocyte globulin
chronic obstructive pulmonary disease. J Thorac
induction in renal transplantation comparing a fixed
Cardiovasc Surg 1995; 109: 106-19.
daily dose with dose adjustment according to T cell
99 Kaplon RJ, PlattJI-o ICwiatkowskiPA, et al. Absence of
monitoring. Transplantation 1995; 59: 1564-8.
hyperacute rejection in pig-to-primate orthotopic pul-
85 Shennib H, Massard G, Reynaud M~ Noirelerc M. monary xenografts. Transplantation 1995; 59: 410-6.
Efficacy of OKT3 therapy for acute rejection in isolat- 100 Ramsey SD, Patrick DI-o Albert RK, Larson EB, Wood
ed lung transplantation. J Heart Lung Transplant DE, Raghu G. The cost-effectiveness of lmag transplan-
1994; 13: 514-9. tation. A pilot study. Chest 1995; 108: 1594-601.
86 CalhoonJH, Nichols L, Davis R, et al. Single lung
transplantation. Factors in postoperative
cytomegalovirus infection. J Thorac Cardiovasc Surg
1992; 103: 21-6.
87 Arm#age JM, Fricker FJ, ICurland G, et al. Pediatric
lung transplantation. The years 1985 to 1992 and the
clinical trial of FK 506. J Thorac Cardiovasc Surg
1993; 105: 337-45.
88 Griffith BP, Bando K, Hardesty RL, et al. A prospec-
tive randomized trial of FK506 versus cyclosporine