Lung Transplant Dave Sweet. CASE You are currently the fellow working at VGH and as you come in Monday morning the charge nurse tells you that there are

Lung TransplantLung Transplant

Dave SweetDave Sweet

CASECASE

You are currently the fellow working You are currently the fellow working at VGH and as you come in Monday at VGH and as you come in Monday morning the charge nurse tells you morning the charge nurse tells you that there are several transplants that there are several transplants going on today including a lung going on today including a lung transplant and that we are holding a transplant and that we are holding a bed. You have several resident bed. You have several resident working with you that are very excited working with you that are very excited and they start firing questions off…. and they start firing questions off….

CASECASE

What diseases are currently we What diseases are currently we doing lung transplants for?doing lung transplants for?

1)1) Alpha1-antitrypsinAlpha1-antitrypsin2)2) CFCF3)3) COPDCOPD4)4) IPF (UIP and occ NSIP)IPF (UIP and occ NSIP)5)5) IPAH (including Eisenmengers)IPAH (including Eisenmengers)6)6) SarcoidosisSarcoidosis

CASECASE

What are the general goals for What are the general goals for determining the appropriateness of determining the appropriateness of a lung transplant in a individual a lung transplant in a individual patient?patient?

General PrinciplesGeneral Principles

Need to consider the natural history Need to consider the natural history and prognosis of primary disease and and prognosis of primary disease and weigh against projected survival post weigh against projected survival post transplant. transplant.

Ultimate goal= Ultimate goal= Obtain max mileage from native lung, Obtain max mileage from native lung,

conferring a greater overall survival conferring a greater overall survival time with new lung.time with new lung.

Avoiding death on the waiting list. Avoiding death on the waiting list.


Consider quality of life while on Consider quality of life while on waiting list compared to quality of waiting list compared to quality of life with new lung. life with new lung.

Traditionally, looked at the median Traditionally, looked at the median 2-year posttransplant survival rate 2-year posttransplant survival rate and compared this to projected and compared this to projected survival with underlying condition. survival with underlying condition.

When former=longer….patients are When former=longer….patients are transplant candidates.transplant candidates.


2 year survival rate is not arbitrary 2 year survival rate is not arbitrary number. Two reasons why used.number. Two reasons why used.

1)1) Average waiting time is around 2 Average waiting time is around 2 yrs. yrs.

2)2) Based on disease the first month Based on disease the first month mortality varies greatly. mortality varies greatly.

……..but then the mortality decreases ..but then the mortality decreases relatively linearly. This will relatively linearly. This will compensate for this. compensate for this.

CASECASE

Do the survival rates for different Do the survival rates for different diseases vary post transplant? diseases vary post transplant? What is the generally quoted first What is the generally quoted first month mortality?month mortality?

CASECASE

First month mortality quoted as 7% to 24%

CASECASE

Which diseases are thought to have Which diseases are thought to have the greatest survival advantages? the greatest survival advantages? Which diseases are questionable?Which diseases are questionable?

Survival advantage?Survival advantage?

Use of time-dependent, Use of time-dependent, nonproportional hazard models, nonproportional hazard models, equity points, and crossover points.equity points, and crossover points.

Survival benefit demonstrated with:Survival benefit demonstrated with:1)1) CFCF2)2) IPFIPF3)3) IPAHIPAH

Critical Care Aspects of Lung Transplantation. Journal of Intensive Care Med 19(2); 2004Critical Care Aspects of Lung Transplantation. Journal of Intensive Care Med 19(2); 2004


However, also raised questions about any However, also raised questions about any survival benefit for px withsurvival benefit for px with

1)1) COPDCOPD

2)2) Eisenmener syndromeEisenmener syndrome

But in addition to survival, quality of life But in addition to survival, quality of life also needs to be taken into consideration. also needs to be taken into consideration.

ie) COPD px changes in quality-adjusted life-ie) COPD px changes in quality-adjusted life-years may be sufficient to justify years may be sufficient to justify transplantation.transplantation.


CASECASE

What are the indications for lung What are the indications for lung transplantation for these various transplantation for these various diseases based on the ATS 1998 diseases based on the ATS 1998 consensus statement?consensus statement?

IndicationsIndications

COPDCOPD FEV1< 25% (without reversibility)FEV1< 25% (without reversibility) And/or PaCO2 >55 and/or elevated PAP And/or PaCO2 >55 and/or elevated PAP

with progressive deteriorationwith progressive deterioration Preference to those px with: Preference to those px with: - elevated PaCO2 with progressive elevated PaCO2 with progressive

deteriorationdeterioration- require long term oxygen therapy.require long term oxygen therapy.Nathan et al. Lung Transplantation: Disease-Specific Considerations for referral. Chest Nathan et al. Lung Transplantation: Disease-Specific Considerations for referral. Chest

2005;127:1006-10162005;127:1006-1016


Interesting……the level of subjective Interesting……the level of subjective dyspnea my be a better predictor of dyspnea my be a better predictor of mortality than FEV1.mortality than FEV1.

ie) grade IV dyspnea= stopping to ie) grade IV dyspnea= stopping to take a breath during 100 yrd walk. take a breath during 100 yrd walk.

- median survival of 3 yrs, which is - median survival of 3 yrs, which is comparable to 3 yr posttransplant comparable to 3 yr posttransplant survival rate (61%)survival rate (61%)

In contrast, FEV1<35% pred had a In contrast, FEV1<35% pred had a median survival of 5 yrs.median survival of 5 yrs.


Currently several other models being Currently several other models being investigated which incorporate a number of investigated which incorporate a number of diff parameters such as the BODE index.diff parameters such as the BODE index.

BBody weight, ody weight, OObstruction, bstruction, DDyspnea level, yspnea level, EExercise tolerance.xercise tolerance.

Score out of 10. Score out of 10. 7-10=80% mort at 52 months (transplant 7-10=80% mort at 52 months (transplant

cand)cand) <7= 5 yr mort of <50% (not transplant cand)<7= 5 yr mort of <50% (not transplant cand)


IPF:IPF: Divided now into UIP and NSIPDivided now into UIP and NSIP UIP=When diagnosed should be UIP=When diagnosed should be

referred!!!referred!!! Traditionally, break points at FVC of Traditionally, break points at FVC of

60-70% and DLCO of 50-60% are 60-70% and DLCO of 50-60% are indicative for poor outcome. Very indicative for poor outcome. Very inconsistent. inconsistent.


Other models look at DLCO and Other models look at DLCO and HRCT scan to help predict mortality HRCT scan to help predict mortality (May see in future!)(May see in future!)

Also, one of the most sensitive Also, one of the most sensitive markers may be desaturation to less markers may be desaturation to less than 89% during a 6 min walk. than 89% during a 6 min walk.

If able to maintain sats may be able If able to maintain sats may be able to defer transplant referral. to defer transplant referral.


NSIP:NSIP: True NSIP have much better True NSIP have much better

prognosis and majority will not need prognosis and majority will not need transplant.transplant.

Subgroup which may require include:Subgroup which may require include:

1) DLCO <35% and/or a dec in DLCO of 1) DLCO <35% and/or a dec in DLCO of >15% have shown to have mortality >15% have shown to have mortality similar to UIP with median survival of similar to UIP with median survival of 2 yrs. 2 yrs.


CF:CF: FEV1 <30% or FEV1 <30% or Rapid progressive resp deterioration Rapid progressive resp deterioration

with FEV1 >30% (inc hosp, rapid fall with FEV1 >30% (inc hosp, rapid fall in FEV1, massive hemoptysis, inc in FEV1, massive hemoptysis, inc cachexia)cachexia)

Room air PaCO2 >50 or PaO2 <55.Room air PaCO2 >50 or PaO2 <55. Woman whose condition is Woman whose condition is

deteriorating rapidly. deteriorating rapidly.


IPAH:IPAH: Medical management has improved Medical management has improved

greatly. greatly. 1990= 10.5% of all lung transplants.1990= 10.5% of all lung transplants. 2001=3.6% of all lung transplants.2001=3.6% of all lung transplants. Should exhaust all medical Should exhaust all medical

management before consider management before consider transplant.transplant.


NYHA class III or IV after 3 months NYHA class III or IV after 3 months of IV epoprostenol have 2 yr survival of IV epoprostenol have 2 yr survival of 46% and should be considered for of 46% and should be considered for transplant. transplant.

NYHA class I and II= 93% and not NYHA class I and II= 93% and not candidate. candidate.


Sarcoidosis (common disease, rare Sarcoidosis (common disease, rare transplant)transplant)

In 1998 guideline no official In 1998 guideline no official recommendation.recommendation.

Need to have stage IV. Advanced fibrotic Need to have stage IV. Advanced fibrotic changes, honey-combing, hilar retraction, changes, honey-combing, hilar retraction, bullae, cysts, and emphysema.bullae, cysts, and emphysema.

Also reasonable when FVC<50% and/or Also reasonable when FVC<50% and/or FEV1 <40%. FEV1 <40%.

CASECASE

After you clearly describe the After you clearly describe the answers to the above questions answers to the above questions your staff speaks up and asks you if your staff speaks up and asks you if you are familiar with the Lung you are familiar with the Lung Allocation Score (LAS).Allocation Score (LAS).

What is the LAS? Why was it What is the LAS? Why was it designed?designed?

LASLAS

In Canada we determine how organs In Canada we determine how organs or allocated by:or allocated by:

Size of patientSize of patient ABO matching (Not HLA matching)ABO matching (Not HLA matching) Time on the list. Time on the list.

Kozower et al. The impact of the lung allocation score on short-term transplant outcomes: A Kozower et al. The impact of the lung allocation score on short-term transplant outcomes: A multicenter study. J thorac Cardiovasc Surg 2008;135:166-77multicenter study. J thorac Cardiovasc Surg 2008;135:166-77

LASLAS

In the US:In the US: Organ procurement and transplantation Organ procurement and transplantation

network (OPTN) began allocating lungs in network (OPTN) began allocating lungs in 1990 based on size, blood type and amount of 1990 based on size, blood type and amount of time candidate had spent on waiting list.time candidate had spent on waiting list.

1995, minor change when 3 months credit 1995, minor change when 3 months credit given to IPF px to offset their inc mortality. given to IPF px to offset their inc mortality. (Not done in Canada)(Not done in Canada)

To better list px according to medical urgency To better list px according to medical urgency and expected benefit the LAS was developed.and expected benefit the LAS was developed.

LASLAS

Developed by multivariate modeling Developed by multivariate modeling and approved by OPTN in 2004. and approved by OPTN in 2004. Implemented in May 2005. Implemented in May 2005.

Three main objectives are:Three main objectives are:

1)1) Reduce deaths on transplant listReduce deaths on transplant list

2)2) Inc transplant benefit for lung Inc transplant benefit for lung recipientsrecipients

3)3) Ensure efficient and equitable Ensure efficient and equitable allocation of organsallocation of organs

LASLAS

Gives a score between 1-100.Gives a score between 1-100. Weighted combination of predicted Weighted combination of predicted

risk of death during the following risk of death during the following year on the waiting list and the year on the waiting list and the predicted likelyhood of survival predicted likelyhood of survival during the first year after transplant. during the first year after transplant.

CASECASE

Is there any evidence that it is Is there any evidence that it is working? working?

First year of implementation compared to First year of implementation compared to previous year. previous year.

170 in each group.170 in each group. Dec in waiting times (680 to 445 days). Dec in waiting times (680 to 445 days). Dec death on waiting list (74 to 51…30%)Dec death on waiting list (74 to 51…30%) Determined that there was a switch with Determined that there was a switch with

inc in IPF px and dec in COPD and CF.inc in IPF px and dec in COPD and CF. Inc in primary graft dysfunction (14.1 to Inc in primary graft dysfunction (14.1 to

22.9%).22.9%). Inc in ICU stay (5.7 to 7.8 days).Inc in ICU stay (5.7 to 7.8 days). Hosp mort and 1 yr survival were similar. Hosp mort and 1 yr survival were similar.

Concluded that the LAS is doing what it was Concluded that the LAS is doing what it was designed to do.designed to do.

Reason why inc in PGD is likely due to higher Reason why inc in PGD is likely due to higher number of retransplants and IPF which both number of retransplants and IPF which both are established risk factors for PGD. are established risk factors for PGD.

When controlled for Dx, the rates of PGD When controlled for Dx, the rates of PGD were no longer different. were no longer different.

This also explains the inc in ICU stay, mech This also explains the inc in ICU stay, mech vent.vent.

Most important…..no change in mortality. Most important…..no change in mortality.

Donor criteria?Donor criteria?

Less than 20% of organ Less than 20% of organ donors possess lungs suitable donors possess lungs suitable

for transplantationfor transplantation

Age <40 years (heart-lung), <50 years Age <40 years (heart-lung), <50 years (lung) (lung)

Smoking history less than 20 pack-years Smoking history less than 20 pack-years Arterial partial oxygen pressure of 140 Arterial partial oxygen pressure of 140

mm Hg on a fraction of inspired oxygen mm Hg on a fraction of inspired oxygen (FIO2) of 40% or 300 mm Hg on an FIO2 (FIO2) of 40% or 300 mm Hg on an FIO2 of 100% of 100%

Normal chest x-ray Sputum free of Normal chest x-ray Sputum free of bacteria, fungi, or significant numbers of bacteria, fungi, or significant numbers of white blood cells on Gram and fungal white blood cells on Gram and fungal staining staining

Bronchoscopy showing absence of Bronchoscopy showing absence of purulent secretions or signs of aspiration purulent secretions or signs of aspiration

Absence of thoracic trauma Absence of thoracic trauma Human immunodeficiency virus negative Human immunodeficiency virus negative

CASECASE

You learn that the patient is a 58 yo male You learn that the patient is a 58 yo male with severe COPD. Other PMHx includes a with severe COPD. Other PMHx includes a NSTEMI 8 yrs prev, HTN, NSTEMI 8 yrs prev, HTN, hypercholesterolemia. Pre-op ECHO results hypercholesterolemia. Pre-op ECHO results show good biventricular fxn with PAS=33 show good biventricular fxn with PAS=33 mmHg via TRJ. Pre-op cath results show mmHg via TRJ. Pre-op cath results show clean coronaries and right heart cath clean coronaries and right heart cath confirms the right sided pressures. Preop confirms the right sided pressures. Preop PFT show a PEV1 of 25% and moderate to PFT show a PEV1 of 25% and moderate to severe airtrapping. They are doing a single severe airtrapping. They are doing a single right lung transplant and no plan for bypass. right lung transplant and no plan for bypass.

CASECASE

8) How is the choice for a single vs a 8) How is the choice for a single vs a double lung transplant made? In double lung transplant made? In what situations is a double lung what situations is a double lung preferred?preferred?

Single vs Double?Single vs Double?

Based on numerous factors such as:Based on numerous factors such as: DiseaseDisease AgeAge ComorbiditiesComorbidities Institutional biasesInstitutional biases Organ availabilityOrgan availability Emergency of procedureEmergency of procedure


Majority done in Canada are single lung Majority done in Canada are single lung transplants.transplants.

First isolated single lungs were done for First isolated single lungs were done for pulmonary fibrosis and this continues to pulmonary fibrosis and this continues to be the norm. be the norm.

COPD originally thought not possible to COPD originally thought not possible to receive single lung transplants.receive single lung transplants.

First done in 1989 by Mal and First done in 1989 by Mal and colleaguescolleagues



Currently a standard throughout the country. Currently a standard throughout the country. Specifically, in COPD if px is of shorter Specifically, in COPD if px is of shorter

stature and older do better.stature and older do better. Pulmonary HTN= single or double but if Pulmonary HTN= single or double but if

choose single expect to have more difficulty in choose single expect to have more difficulty in first few days. Many centers mandate only first few days. Many centers mandate only bilateral.bilateral.

Bilateral transplants are mandatory for px Bilateral transplants are mandatory for px with CF and bronchiectasis.with CF and bronchiectasis.



Bilateral lung transplants for Bilateral lung transplants for mycetomas or other chronic fungal mycetomas or other chronic fungal or mycobacterial infectionsor mycobacterial infections

Many larger centers are now Many larger centers are now favoring bilateral transplants. favoring bilateral transplants. Specifically the Duke University Specifically the Duke University Medical Center. Medical Center.



1)1) Feel do not exclude other patient in Feel do not exclude other patient in many cases.many cases.

2)2) If single lung is “marginal” for If single lung is “marginal” for transplant, taking both will provide transplant, taking both will provide adequate function. adequate function.

3)3) Early post-op management is easier Early post-op management is easier with bilateralwith bilateral


Additionally, in 225 px who survive 6 Additionally, in 225 px who survive 6 months. months.

Single lung transplant (as compared to Single lung transplant (as compared to bilateral) was a significant risk for BOS in bilateral) was a significant risk for BOS in multivariate Cox model (HR=2.08, multivariate Cox model (HR=2.08, p=0.001)p=0.001)

? If immunologic advantages of bilateral ?? If immunologic advantages of bilateral ?

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


A recent review of the United Network of A recent review of the United Network of Organ Sharing lung transplant database of Organ Sharing lung transplant database of 2260 transplants for emphysema compared 2260 transplants for emphysema compared single vs double lung transplants.single vs double lung transplants.

No difference in 30 day mortality but long No difference in 30 day mortality but long term survival data favored bilateral lung term survival data favored bilateral lung transplants for individuals <60 yrs of age.transplants for individuals <60 yrs of age.

Bilat were older and more women. ? How to Bilat were older and more women. ? How to interpret?interpret?

Meyer et al. J heart Lung Transplant 2001;20:935-941.Meyer et al. J heart Lung Transplant 2001;20:935-941.

CaseCase

9) In what situations will a lung 9) In what situations will a lung transplant be done on bypass? Why transplant be done on bypass? Why if done on bypass is it relevant to if done on bypass is it relevant to post-op management?post-op management?

Bypass?Bypass? Most adult transplants can be done without Most adult transplants can be done without

CPB. A number of specific situations will CPB. A number of specific situations will necessitate CPB.necessitate CPB.

1)1) Primary or secondary pulmonary htn are Primary or secondary pulmonary htn are most safely done on bypass.most safely done on bypass.

2)2) Px with CF likely have such voluminous Px with CF likely have such voluminous purulent secretions that independent purulent secretions that independent ventilation is impossible.ventilation is impossible.

3)3) During bilateral transplant early graft During bilateral transplant early graft dysfxn of the first transplanted lung dysfxn of the first transplanted lung (reperfusion) preventing single lung vent. (reperfusion) preventing single lung vent.

4)4) If native lung is unable to sustain patient If native lung is unable to sustain patient with single lung ventilation. with single lung ventilation.

Bypass?Bypass?

Why relevant to post-op care?Why relevant to post-op care?

1) If get significant PGD it is unlikely the patient 1) If get significant PGD it is unlikely the patient can be supported on single lung ventilation.can be supported on single lung ventilation.

2) Bypass is a significant risk factor for PGD!!2) Bypass is a significant risk factor for PGD!!

Most recent large study by Dalibon, which Most recent large study by Dalibon, which reviewed 140 LT, confirmed that CPB was reviewed 140 LT, confirmed that CPB was associated with longer MV, more pulm edema, associated with longer MV, more pulm edema, more transfusions and inc early mortality!!more transfusions and inc early mortality!!

Dalibon et. al. J Cardiothorac Vasc Anesth 2006;20:668-672.Dalibon et. al. J Cardiothorac Vasc Anesth 2006;20:668-672.

CASECASE

You hear that the case is finishing up. You hear that the case is finishing up. There was minimal surgical difficulty the There was minimal surgical difficulty the lung was implanted using continuous 3/0 lung was implanted using continuous 3/0 polypropylene sutures for the bronchial polypropylene sutures for the bronchial anastomosis (end-end-technique), anastomosis (end-end-technique), continuous 4/0 polypropylene sutures for continuous 4/0 polypropylene sutures for the pulmonary vein to left atrial the pulmonary vein to left atrial anastomosis, and continuous 5/0 anastomosis, and continuous 5/0 polypropylene sutures for the pulmonary polypropylene sutures for the pulmonary arterial anastomosis. arterial anastomosis.

CASECASE Unfortunately you hear that they need to Unfortunately you hear that they need to

do the case on bypass as they were unable do the case on bypass as they were unable to do the transplant on single lung to do the transplant on single lung ventilation. The overall ischemia time was ventilation. The overall ischemia time was 6 hours and 8 minutes for the lung. The 6 hours and 8 minutes for the lung. The post-transplant bronch looked pristine and post-transplant bronch looked pristine and the TEE looked good. The patient is the TEE looked good. The patient is brought to ICU post-op stable on AC and brought to ICU post-op stable on AC and FIO2 of 100% and quickly weaned to 80%. FIO2 of 100% and quickly weaned to 80%. CVP=12 CI=3.5, PA=40/18. (If the nurse CVP=12 CI=3.5, PA=40/18. (If the nurse said the PAWP=16…what would you say??)said the PAWP=16…what would you say??)

CASECASE

10) Generally what ventilator 10) Generally what ventilator settings would you like post settings would you like post transplant px to be on? What about transplant px to be on? What about this patient? What is your general this patient? What is your general plan to wean the ventilator? plan to wean the ventilator?

Ventilation?Ventilation?

Many centers prefer a PC ventilation so Many centers prefer a PC ventilation so as to limit peak airway pressures (<40) as to limit peak airway pressures (<40) and prevent barotrauma to the brochial and prevent barotrauma to the brochial anastomosis.anastomosis.

Plat pressure should additionally be Plat pressure should additionally be limited to less than 30 to 35 mmHg. limited to less than 30 to 35 mmHg.

Minimize Fio2 as quickly as possible.Minimize Fio2 as quickly as possible.



This patient?This patient? Due to the very compliant native lung with Due to the very compliant native lung with

potential for air trapping and the relatively potential for air trapping and the relatively stiff transplant lung….need to be aware of stiff transplant lung….need to be aware of balance. balance.

To begin, as long as oxygenation is not a issue. To begin, as long as oxygenation is not a issue. Ventilation as if to prevent air trapping in Ventilation as if to prevent air trapping in native lung.native lung.

Min PEEP, adequate expiratory phase with PC. Min PEEP, adequate expiratory phase with PC. Can still use EEP to determine if airtrapping. Can still use EEP to determine if airtrapping.



Generally want to get off the ventilator as Generally want to get off the ventilator as soon as possible. soon as possible.

Use adequate analgesia via epidural or Use adequate analgesia via epidural or paravertebral (recent metaanalysis and found paravertebral (recent metaanalysis and found paravertebral block had lower rate of resp paravertebral block had lower rate of resp complications and side effects) ….wake and complications and side effects) ….wake and wean. wean.

If have standard PS weaning protocol it If have standard PS weaning protocol it should be used as usual. should be used as usual.

Plan to have extubated in 24 to 48 hrs ideally!Plan to have extubated in 24 to 48 hrs ideally!Davies et. al. Br J Anaesth 2006; 96:418-426.Davies et. al. Br J Anaesth 2006; 96:418-426.

CASECASE

11) Generally discuss your fluid 11) Generally discuss your fluid management post op. What management post op. What variables are you balancing with variables are you balancing with your fluid management? your fluid management?

Fluid ManagementFluid Management

Careful fluid management is necessary to Careful fluid management is necessary to avoid substantial transplant lung edema.avoid substantial transplant lung edema.

Usually aim for a negative fluid balance from Usually aim for a negative fluid balance from the get go. Def aim for negative balance in the get go. Def aim for negative balance in the first 48hrs. the first 48hrs.

Minimal fluid and if require volume use colloid Minimal fluid and if require volume use colloid or blood.or blood.

Some centers will target a CVP of <7 mmH20, Some centers will target a CVP of <7 mmH20, with systemic perfusion supported by with systemic perfusion supported by pressors.pressors.

Pilcher et. al. A high CVP is associated with prolonged mech vent and inc mortality following Pilcher et. al. A high CVP is associated with prolonged mech vent and inc mortality following lung transplantation. J Thoracic Cardiovasc Surg 2005;129:912-918.lung transplantation. J Thoracic Cardiovasc Surg 2005;129:912-918.

Fluid ManagementFluid Management Retrospective study of 118 px.Retrospective study of 118 px. After controlling for CV diz and After controlling for CV diz and

vasopressors, CVP was correlated with vasopressors, CVP was correlated with duration of MV, with a CVP >7 also being duration of MV, with a CVP >7 also being associated with higher ICU and hosp associated with higher ICU and hosp mortality.mortality.

Unclear whether a strategy aimed at Unclear whether a strategy aimed at keeping CVP less than 7 would alter keeping CVP less than 7 would alter outcome or if a marker of severity of outcome or if a marker of severity of illness. illness.

Pilcher et. al. A high CVP is associated with prolonged mech vent and inc mortality Pilcher et. al. A high CVP is associated with prolonged mech vent and inc mortality following lung transplantation. J Thoracic Cardiovasc Surg 2005;129:912-918.following lung transplantation. J Thoracic Cardiovasc Surg 2005;129:912-918.

Fluid ManagementFluid Management Obviously need to balance against the Obviously need to balance against the

risk of renal insufficiency. risk of renal insufficiency. Many of these patient my have Many of these patient my have

CRF….specifically the CF px. (why?). CRF….specifically the CF px. (why?). Additionally cyclosporine or tacrolimus Additionally cyclosporine or tacrolimus

may impair renal fxn. Watch levels may impair renal fxn. Watch levels closely post-op. closely post-op.

Titrate volume to u/o. Previous many Titrate volume to u/o. Previous many centers still using “renal dose centers still using “renal dose dopamine” in this setting. No evidence. dopamine” in this setting. No evidence.

CASECASE

12)Although our patient remains 12)Although our patient remains hemodynamically stable. Why is hemodynamically stable. Why is shock in these patients need to be shock in these patients need to be quickly identified and diagnosed? quickly identified and diagnosed?

CASECASE

These patients should not be shocky!!These patients should not be shocky!! ““NEED TO MAKE DIAGNOSIS” NEED TO MAKE DIAGNOSIS”

(Dr George Isac) (Dr George Isac) Bleeding? Anastamosis?(watch CTs Bleeding? Anastamosis?(watch CTs

and hgb)and hgb) Obstructive? Anastamosis? Obstructive? Anastamosis? Cardiogenic?Cardiogenic? Infection/sepsis?Infection/sepsis?

CASECASE

Judicious resuscitation (colloid) and Judicious resuscitation (colloid) and vasopressors vasopressors

STAT ECHO (TEE)STAT ECHO (TEE) Notify the SurgeonNotify the Surgeon ? Mobilize ECMO early?? Mobilize ECMO early? Is their a benign reason why they Is their a benign reason why they

may be requiring increasing may be requiring increasing vasopressor support?vasopressor support?

CASECASE

After initially settling the patient in After initially settling the patient in and continuing on your rounds the and continuing on your rounds the RT approaches you and states that RT approaches you and states that the FIO2 requirements are back up the FIO2 requirements are back up to 100% after a brief period at 50% to 100% after a brief period at 50% and hypoxia is becoming an issue. A and hypoxia is becoming an issue. A stat CXR was done. stat CXR was done.

CASECASE

CASECASE

13) What is your differential for 13) What is your differential for early respiratory failure in the lung early respiratory failure in the lung transplant? What are the risk transplant? What are the risk factors for early respiratory failure?factors for early respiratory failure?

Early Respiratory FailureEarly Respiratory Failure DDx:DDx:1)1) Reperfusion injury (55%)Reperfusion injury (55%)2)2) Periop cardiovascular(MI, arrhythmia, Periop cardiovascular(MI, arrhythmia,

CHF) /haemorrhagic (36%)CHF) /haemorrhagic (36%)3)3) Anatomic complicationsAnatomic complications4)4) Infectious (bacterial and CMV)Infectious (bacterial and CMV)5)5) Rejection (hyperacute=rare and Rejection (hyperacute=rare and

acute=common)acute=common)6)6) PneumothoraxPneumothorax7)7) PEPEChatila el. al. Resp failure after lung transplant. Chest 2003;123:165-173.Chatila el. al. Resp failure after lung transplant. Chest 2003;123:165-173.

Early Respiratory FailureEarly Respiratory Failure

Risk factors:Risk factors:

1)1) Preop pulmonary htnPreop pulmonary htn

2)2) Rt vent dysfunctionRt vent dysfunction

3)3) Prolonged ischemic timeProlonged ischemic time

4)4) CPBCPB

Chatila el. al. Resp failure after lung transplant. Chest 2003;123:165-173.Chatila el. al. Resp failure after lung transplant. Chest 2003;123:165-173.

CASECASE

14) Briefly describe Reperfusion 14) Briefly describe Reperfusion injury, Primary Graft failure. What injury, Primary Graft failure. What can we do to help prevent can we do to help prevent Reperfusion injury before and after Reperfusion injury before and after the transplant? How do you manage the transplant? How do you manage it? (specifically in our patient?) it? (specifically in our patient?)

Ischemia-Reperfusion Ischemia-Reperfusion InjuryInjury

Typically manifests in the first 72 h Typically manifests in the first 72 h after transplant.after transplant.

Development of airspace disease, Development of airspace disease, progressive hypoxemia, and inc in progressive hypoxemia, and inc in pulmonary pressures (reflective both pulmonary pressures (reflective both epithelial and endothelia injury)epithelial and endothelia injury)

When PaO2/FiO2 ratio below 200, When PaO2/FiO2 ratio below 200, termed primary graft failure.termed primary graft failure.

Granton, J. Update of early resp failure in the transplant recipient. Current Opinion in Granton, J. Update of early resp failure in the transplant recipient. Current Opinion in Critical Care 2006;12:19-24.Critical Care 2006;12:19-24.


Recent 2004 publication identified Recent 2004 publication identified several risk factors:several risk factors:

CPBCPB BMI >25kg/m2BMI >25kg/m2 Immediate elevated PASImmediate elevated PAS Trend in oxygenation index over Trend in oxygenation index over

24hrs24hrs Elevated APACHE IIElevated APACHE IISekine et al. J Heart Lung Transplant 2004;23:96-104Sekine et al. J Heart Lung Transplant 2004;23:96-104


Additionally, a review of 7 French Additionally, a review of 7 French transplant centers and 752 px over 12 yrs.transplant centers and 752 px over 12 yrs.

Found graft ischemic time associated with Found graft ischemic time associated with the PaO2/FiO2 ration measured at 6 hrs.the PaO2/FiO2 ration measured at 6 hrs.

30 day mortality was associated with a 30 day mortality was associated with a lower PaO2/FiO2 ratio at 6 hrs. lower PaO2/FiO2 ratio at 6 hrs.

Identified cold ischemic time of 330 min Identified cold ischemic time of 330 min (5.5hr) as distinguishing between px who (5.5hr) as distinguishing between px who had a uncomplicated course vs those who had a uncomplicated course vs those who did not. (Max accepted is 6-8hrs)did not. (Max accepted is 6-8hrs)

Thabu et al. Am J Respir Crit Care Med 2005;171:786-791.Thabu et al. Am J Respir Crit Care Med 2005;171:786-791.Oto et al. J Thorac Cardiovasc Surg 2005;130:180-186.Oto et al. J Thorac Cardiovasc Surg 2005;130:180-186.


Ischemia-Reperfusion Injury also Ischemia-Reperfusion Injury also associated with long-term consequences.associated with long-term consequences.

Retrospective cohort study of 255 LT px. Retrospective cohort study of 255 LT px. Christie et al reported a 30 day mort of Christie et al reported a 30 day mort of

63.3% compared to 8.8% in px with and 63.3% compared to 8.8% in px with and without reperfusion injury.without reperfusion injury.

Median hosp was longer (47 vs 15 days)Median hosp was longer (47 vs 15 days) Mech vent longer (15 vs 1 day)Mech vent longer (15 vs 1 day) Lower exercise capacity as assessed by 6 Lower exercise capacity as assessed by 6

min walk distance at 12 months.min walk distance at 12 months.

Christie et al. Chest 2005;127:161-165.Christie et al. Chest 2005;127:161-165.


Pathogenesis:Pathogenesis: Variety of perturbations implicated.Variety of perturbations implicated. Factors relating to:Factors relating to:

1)1) DonorDonor

2)2) Method of graft preservationMethod of graft preservation

3)3) Effects of reperfusion following Effects of reperfusion following period of ischemiaperiod of ischemia


The Lungs may be made susceptible from The Lungs may be made susceptible from cytokine-mediated damage in px with cytokine-mediated damage in px with elevated ICP and compounded following elevated ICP and compounded following cold preservation of the grafts.cold preservation of the grafts.

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


How can we help prevent ischemia-How can we help prevent ischemia-reperfusion injury? reperfusion injury?

Can divide into:Can divide into:

1)1) Pre-transplant interventionsPre-transplant interventions

2)2) Peri-surgical interventionsPeri-surgical interventions

3)3) Post-surgical interventionsPost-surgical interventions



Pre-Surgical interventions:Pre-Surgical interventions: Preservation solution…specifically a Preservation solution…specifically a

low-potassium dextran solution low-potassium dextran solution provides superior preservation over provides superior preservation over high potassium preservation solutions.high potassium preservation solutions.

In addition, nitric oxide added to the In addition, nitric oxide added to the flush during harvest provides a flush during harvest provides a preservation advantage. (not well preservation advantage. (not well studied)studied)

Maccherini et al. Transplantation. 1991;52:621-626Maccherini et al. Transplantation. 1991;52:621-626Yamashita et al. Ann thorac Surg. 1996;62:791-797Yamashita et al. Ann thorac Surg. 1996;62:791-797


It is known that lung hyperinflation It is known that lung hyperinflation is a excellent model of pulmonary is a excellent model of pulmonary edema….therefore care should be edema….therefore care should be taken to avoid during harvest and taken to avoid during harvest and storage.storage.


Peri-Surgical interventions:Peri-Surgical interventions: Lick and colleagues reported a small Lick and colleagues reported a small

series where using leukocyte-filtered series where using leukocyte-filtered modified perfusate is pumped modified perfusate is pumped through the lung at time of through the lung at time of reperfusion. In case report….no reperfusion. In case report….no ischemia-reperfusion injury. ischemia-reperfusion injury.

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


Post-surgical interventions:Post-surgical interventions: TP-10 inhibitorTP-10 inhibitor

- One of few randomized trials in lung - One of few randomized trials in lung transplantation, using soluble transplantation, using soluble complement receptor-1 inhibitor led complement receptor-1 inhibitor led to reduction in duration of mech vent. to reduction in duration of mech vent.

- Interestingly, greatest effect in px - Interestingly, greatest effect in px who received bypass.who received bypass.


NONO- Early preclinical and uncontrolled Early preclinical and uncontrolled

reports suggested that admin of NO reports suggested that admin of NO either prior to or shortly after either prior to or shortly after reperfusion injury could dec severity of reperfusion injury could dec severity of disease.disease.

- Recent controlled clinical trial failed to Recent controlled clinical trial failed to show benefit when inhaled 10 min after show benefit when inhaled 10 min after reperfusion. reperfusion.

Meade et al. Am J Respir Crit Care Med 2003;167:1483-1489.Meade et al. Am J Respir Crit Care Med 2003;167:1483-1489.


NONO- Another recent trial by Perrin.Another recent trial by Perrin.- RCT in 30 bilateral lung transplants.RCT in 30 bilateral lung transplants.- 20 ppm iNO at time of reperfusion vs 20 ppm iNO at time of reperfusion vs

control.control.- Could not identify any reduction in Could not identify any reduction in

extravasular lung water (p=0.61) or extravasular lung water (p=0.61) or improvement in gas exchange (p=0.61).improvement in gas exchange (p=0.61).

- Future studies needed.Future studies needed.Perrin et al. Chest 2006;129:1024-1030Perrin et al. Chest 2006;129:1024-1030


ICU management:ICU management: Adoption of lung protective strategy Adoption of lung protective strategy

would seem reasonable. (only one rat would seem reasonable. (only one rat study has actually looked at this).study has actually looked at this).

““In refractory hypoxemia use of inhaled In refractory hypoxemia use of inhaled NO, HFO and ECMO may improve gas NO, HFO and ECMO may improve gas exchange.”exchange.”

Granton, J. Update of early resp failure in the transplant recipient. Current Opinion in Critical Granton, J. Update of early resp failure in the transplant recipient. Current Opinion in Critical Care 2006;12:19-24.Care 2006;12:19-24.


What about our patient??What about our patient?? In COPD single lung Tx that develop In COPD single lung Tx that develop

reperfusion injury….dilemmas may arise.reperfusion injury….dilemmas may arise. As px becomes hypoxic and more As px becomes hypoxic and more

aggressive vent/peep strategies are aggressive vent/peep strategies are used….may overdistend native lung.used….may overdistend native lung.

Cause shunting of blood to dysfunctional Cause shunting of blood to dysfunctional allograft.allograft.

Futhermore, if worsens still, mediastinal Futhermore, if worsens still, mediastinal shift may result in impaired venous return.shift may result in impaired venous return.


Better to minimize tidal volumes and lowest Better to minimize tidal volumes and lowest PEEP to gain acceptable oxygenation and PEEP to gain acceptable oxygenation and accepting mild respiratory acidosis (+/- accepting mild respiratory acidosis (+/- novalung??)novalung??)

Place px in lateral decubitus with transplant Place px in lateral decubitus with transplant side up, and aggressive chest physiotherapy.side up, and aggressive chest physiotherapy.

If this fails….should consider independent If this fails….should consider independent lung ventilation.lung ventilation.

Be aware that will be more difficult to clear Be aware that will be more difficult to clear secretions and the ease with which the tube secretions and the ease with which the tube may be dislodged.may be dislodged.

Gavazzeni et al. Chest. 1993;103:297-299.Gavazzeni et al. Chest. 1993;103:297-299.

Prediction of Independent Prediction of Independent Lung Vent.Lung Vent.

Prediction of need for single lung Prediction of need for single lung ventilation?ventilation?

Study looking at 170 px who had single Study looking at 170 px who had single lung transplant for COPD. lung transplant for COPD.

12% required independent lung 12% required independent lung ventilation.ventilation.

Similar in age, sex, ischemic time, and Similar in age, sex, ischemic time, and donor characteristics to those who donor characteristics to those who required conventional ventilation. required conventional ventilation.

Pilcher et al. Predictors of independent lung ventilation: an analysis of 170 single-lung transplantations. Pilcher J Pilcher et al. Predictors of independent lung ventilation: an analysis of 170 single-lung transplantations. Pilcher J Thorac Cardiovasc Surg. 2007 Apr;133(4):1071-7 Thorac Cardiovasc Surg. 2007 Apr;133(4):1071-7


Patients receiving independent lung Patients receiving independent lung ventilation had a greater degree of:ventilation had a greater degree of:

Preoperative airflow limitation Preoperative airflow limitation (FVC1/FVC)(FVC1/FVC)

More hyperinflationMore hyperinflation Lower postoperative PaO2/fraction of Lower postoperative PaO2/fraction of

inspired oxygen ratiosinspired oxygen ratios More radiologic mediastinal shiftMore radiologic mediastinal shift More transplant lung infiltrate on the More transplant lung infiltrate on the

postoperative chest radiograph. postoperative chest radiograph.


Multivariate logistic regression analysis Multivariate logistic regression analysis showed that independent lung showed that independent lung ventilation was associated with:ventilation was associated with:

Increasing levels of recipient Increasing levels of recipient hyperinflation (percentage total lung hyperinflation (percentage total lung capacity compared with predicted value; capacity compared with predicted value; odds ratio 1.04;P = .032) odds ratio 1.04;P = .032)

Reduced early postoperative Reduced early postoperative PaO2/fraction of inspired oxygen ratio PaO2/fraction of inspired oxygen ratio (odds ratio 0.96; P = .005) (odds ratio 0.96; P = .005)


Length of ventilation and intensive Length of ventilation and intensive care unit stay and mortality were care unit stay and mortality were higher in the independent lung higher in the independent lung ventilation group. ventilation group.

Among patients who survived to Among patients who survived to hospital discharge, there were no hospital discharge, there were no differences in long-term mortality differences in long-term mortality between the 2 groups. between the 2 groups.


Conclusions= Independent lung Conclusions= Independent lung ventilation predicted by the ventilation predicted by the combination of: combination of:

Increased hyperinflation measured on Increased hyperinflation measured on recipients' preoperative lung function recipients' preoperative lung function tests tests

Low PaO2/fraction of inspired oxygen Low PaO2/fraction of inspired oxygen ratio, indicating graft dysfunction in ratio, indicating graft dysfunction in the immediate postoperative period. the immediate postoperative period.


Another study looking at predictors of Another study looking at predictors of native lung hyperinflation.native lung hyperinflation.

Retrospectively analyzed data from 27 Retrospectively analyzed data from 27 patients who underwent 31 single lung patients who underwent 31 single lung transplantations for emphysema.transplantations for emphysema.

Two groups:Two groups:- 12 patients with development of acute or 12 patients with development of acute or

chronic NLHchronic NLH- 15 patients without development of 15 patients without development of

hyperinflation hyperinflation Yonan. Yonan. Single lung transplantation for emphysema: predictors for native lung hyperinflation. Single lung transplantation for emphysema: predictors for native lung hyperinflation. J Heart Lung Transplant. J Heart Lung Transplant.

1998 Feb;17(2):192-2011998 Feb;17(2):192-201


NLH was defined as: NLH was defined as: Radiologic mediastinal shift with Radiologic mediastinal shift with Flattening of the ipsilateral Flattening of the ipsilateral

diaphragm diaphragm Associated with respiratory Associated with respiratory

dysfunction or hemodynamic dysfunction or hemodynamic instability instability


No differences between the two groups regarding: No differences between the two groups regarding: age age preoperative partial pressure of oxygen preoperative partial pressure of oxygen partial pressure of carbon dioxidepartial pressure of carbon dioxide acid-base statusacid-base status donor lung size and physiological structuredonor lung size and physiological structure side of transplantationside of transplantation primary pathologic conditionprimary pathologic condition rejection scorerejection score infection episodes and obliterative bronchiolitis in infection episodes and obliterative bronchiolitis in

the transplanted lung after operation. the transplanted lung after operation.


Patients with NLH had: Patients with NLH had: Significantly higher preoperative Significantly higher preoperative

mean pulmonary artery pressure > mean pulmonary artery pressure > 30 mm Hg. 30 mm Hg.

Lower mean FEV1.Lower mean FEV1. Higher mean residual volume.Higher mean residual volume.

CASECASE

A quick in and out bronch shows no A quick in and out bronch shows no anatomic abn and on TEE the pulmonary anatomic abn and on TEE the pulmonary veins look good. After a short period of veins look good. After a short period of time you realize that he is deteriorating time you realize that he is deteriorating that the hypoxia is quickly becoming that the hypoxia is quickly becoming refractory. You quickly mobilize ECMO refractory. You quickly mobilize ECMO and after a short time on ECMO the and after a short time on ECMO the patient stabilizes. patient stabilizes.

15) Your staff asks you if you know of any 15) Your staff asks you if you know of any evidence for the use of early ECMO in evidence for the use of early ECMO in these patients? these patients?

ECMOECMO Several publications Several publications

looking at ECMO in this looking at ECMO in this situation.situation.

In the setting of In the setting of pulmonary htn (high risk), pulmonary htn (high risk), early ECMO has been early ECMO has been advocated (experience advocated (experience based).based).

Another review of 17 casesAnother review of 17 cases ECMO may preserve initial ECMO may preserve initial

organ function due to organ function due to reduction in use of reduction in use of injurious ventilation injurious ventilation strategies.strategies.

Dahlberg et al. J Heart Lung Transplant 2004;23:979-984.Dahlberg et al. J Heart Lung Transplant 2004;23:979-984.Pereszlenyi et al. Eur J Cardiothorac Surg 2002;21:858-863.Pereszlenyi et al. Eur J Cardiothorac Surg 2002;21:858-863.

ECMOECMO

More recent publication by Oto at More recent publication by Oto at Alfred Hosp in Melbourne.Alfred Hosp in Melbourne.

Ten transplant recipients from total of Ten transplant recipients from total of 481 (2.1%) were treated with ECMO.481 (2.1%) were treated with ECMO.

Prior to initiation had TEE to exclude Prior to initiation had TEE to exclude lung torsion and pulmonary vasc prob, lung torsion and pulmonary vasc prob, and a retrospective crossmatch to and a retrospective crossmatch to exclude humoral rejection.exclude humoral rejection.

ECMOECMOInitiate 21 days (7-40days)

Initiated after 0-2 days

ECMOECMO

CASECASE

One of your keen residents asks if One of your keen residents asks if there is anyway this could be acute there is anyway this could be acute rejection? Are there any definitive rejection? Are there any definitive tests to prove this is not rejection? tests to prove this is not rejection?

Biopsy!!Biopsy!!

Patients with acute rejection can also have Patients with acute rejection can also have alveolar infiltrates, hypoxemia and systemic alveolar infiltrates, hypoxemia and systemic inflammatory response syndrome. inflammatory response syndrome.

To rule out hyperacute rejection can do a To rule out hyperacute rejection can do a retrospective crossmatch.retrospective crossmatch.

For longer term observation pathologic For longer term observation pathologic assessment of multiple transbronchial biopsy assessment of multiple transbronchial biopsy specimens has proven to be the gold standard.specimens has proven to be the gold standard.

Debate between transbronchial and surgical Debate between transbronchial and surgical biopsy.biopsy.

Trulock et al. Chest. 1992;102:1049-1054.Trulock et al. Chest. 1992;102:1049-1054.

Open Lung BiopsyOpen Lung Biopsy

In 2003 Burns et al looked at 41 patients In 2003 Burns et al looked at 41 patients on mech vent with questionable acute on mech vent with questionable acute rejection that received transbronchial and rejection that received transbronchial and open lung biopsy.open lung biopsy.

Surgical biopsy inc dx of rejection by 33% Surgical biopsy inc dx of rejection by 33% and treatment changes in 15 of the 41. and treatment changes in 15 of the 41.

Currently unresolved debate as previous Currently unresolved debate as previous studies contradicted this finding. studies contradicted this finding.

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

Open Lung BiopsyOpen Lung Biopsy

The risk of open lung biopsy must be The risk of open lung biopsy must be weighed against the risk of simple weighed against the risk of simple empirical therapy for rejection after empirical therapy for rejection after exclusion of infection. exclusion of infection.

Given the consequences of Given the consequences of intensification of intensification of immunosuppression in the immunosuppression in the intubated, critically ill px, open lung intubated, critically ill px, open lung biopsy may be justifiable. biopsy may be justifiable.

CASECASE

Now that the possibility of rejection Now that the possibility of rejection has been brought up…..what are the has been brought up…..what are the different types of rejection? How different types of rejection? How are they treated?are they treated?

RejectionRejection

Hyperacute- humoral based with Hyperacute- humoral based with preformed antibodies to the allograft preformed antibodies to the allograft vascular endotheliumvascular endothelium

- Only anecdotally reported in the - Only anecdotally reported in the literature with lung transplant. literature with lung transplant.

Cellular immune based rejectionsCellular immune based rejections Acute Acute Chronic/bronchiolitis obliterans Chronic/bronchiolitis obliterans

syndrome (BOS)syndrome (BOS)

RejectionRejection

Standard immunosuppressive management:Standard immunosuppressive management: Triple drug combo=cyclosporin, imuran, Triple drug combo=cyclosporin, imuran,

prednisone. prednisone. Methylprednisolone intraop and first 24 hrs. Methylprednisolone intraop and first 24 hrs.

Then steroids suspended for 2 weeks, based Then steroids suspended for 2 weeks, based on experimental and clinical evidence they on experimental and clinical evidence they impede bronchial anastamotic healing.impede bronchial anastamotic healing.

Then oral pred started. Then oral pred started. Some evidence tacrolimus/imuran/steroid may Some evidence tacrolimus/imuran/steroid may

be a better combo. (acute and chronic be a better combo. (acute and chronic rejection)rejection)

RejectionRejection

Acute:Acute: Most common complication following Most common complication following

lung transplantation.lung transplantation. Most recipients experience at least 1 Most recipients experience at least 1

episode in first year.episode in first year. It is clear that there is a association It is clear that there is a association

between frequency and severity of between frequency and severity of acute rejection and subsequent dev of acute rejection and subsequent dev of BOS.BOS.

RejectionRejection

Thus, early detection and alteration of Thus, early detection and alteration of immunosuppression may have a significant immunosuppression may have a significant impact on subsequent reduction of BOS.impact on subsequent reduction of BOS.

S/S:S/S: FeverFever DyspneaDyspnea Dec PaO2Dec PaO2 Fall in vital capacityFall in vital capacity Infiltrates.Infiltrates.

RejectionRejection

After first postop month, CXR freq normal After first postop month, CXR freq normal during episode of acute rejection.during episode of acute rejection.

Obviously, infection can present similarly.Obviously, infection can present similarly. Need to distinguish with transbronch Need to distinguish with transbronch

biopsy and BAL.biopsy and BAL. Tx:Tx: Methylprednisolone 10-15mg/kg for 3-5 Methylprednisolone 10-15mg/kg for 3-5

days.days. 2-3 weeks of oral steroid taper.2-3 weeks of oral steroid taper.

RejectionRejectionSome work by Loubeyre et al, that may be able to use HDCT to Dx acute rejection and avoid TBB (65% sens for rejection, 85% specific for acute lung complication.

RejectionRejection

Maintenance immunosuppression Maintenance immunosuppression regimen should also be scrutinized.regimen should also be scrutinized.

First adjustment from maintenance First adjustment from maintenance cyclosporine is a switch to tacrolimus in cyclosporine is a switch to tacrolimus in event of cyclosporin toxicity or acute event of cyclosporin toxicity or acute rejection episodes despite adequate rejection episodes despite adequate cyclosporine dosage.cyclosporine dosage.

Newer agents such as sirolimus, Newer agents such as sirolimus, leflunomide may be used more in future. leflunomide may be used more in future.

RejectionRejection

Chronic/bronchiolitis obliterans Chronic/bronchiolitis obliterans syndrome(BOS):syndrome(BOS):

70% of graft recipients are dx by 570% of graft recipients are dx by 5thth year. year. Usually presents as a late decline in Usually presents as a late decline in

FEV1 from a post-op baseline. FEV1 from a post-op baseline. Pathologic lesion is broncholitis Pathologic lesion is broncholitis

obliterans.obliterans.

RejectionRejection

Risk Factors:Risk Factors: Episodes of acute rejectionEpisodes of acute rejection Primary Graft dysfunctionPrimary Graft dysfunction CMV pneumonia CMV pneumonia Noncompliance with medsNoncompliance with meds

RejectionRejection

Causes not totally clear.Causes not totally clear. Evidence suggests both alloimmune Evidence suggests both alloimmune

and non-alloimmune mech are and non-alloimmune mech are important (for example GERD).important (for example GERD).

There is evidence that fundoplication There is evidence that fundoplication will lower BOS scores and even will lower BOS scores and even eliminate it in certain individualseliminate it in certain individuals

Cantu et al. Ann THorac Surg 2004;78:1142-51Cantu et al. Ann THorac Surg 2004;78:1142-51

RejectionRejection

Diagnosis- two approaches (definitive Diagnosis- two approaches (definitive proof and diagnosis of exclusion)proof and diagnosis of exclusion)

RejectionRejection

Treatment: (no well established protocol)Treatment: (no well established protocol) Conversion from cyclosporin to Conversion from cyclosporin to

tacrolimus may stabilize progression.tacrolimus may stabilize progression. ?addition of mycophenolate may be ?addition of mycophenolate may be

benificial.benificial. ?sirolimus ?sirolimus ?azithromycin daily is currently being ?azithromycin daily is currently being

investigated and may show promise.investigated and may show promise. Retransplantation? Retransplantation?

CASECASE

17)Could this be infectious? Where 17)Could this be infectious? Where in the complications timeline to in the complications timeline to infectious etiologies usually fit? Are infectious etiologies usually fit? Are there any exceptions? there any exceptions?

Infection post transplantInfection post transplant

Unlikely in this scenario. Unlikely in this scenario. But infection is one of the leading But infection is one of the leading

causes of morbidity and mortality.causes of morbidity and mortality. Immediate post-op bacterial are the Immediate post-op bacterial are the

greatest threat.greatest threat. But candidia or aspergillus or viral But candidia or aspergillus or viral

(herpies or CMV) can also arise.(herpies or CMV) can also arise.Lung transplant: procedure and postoperateive management. 2008 Uptodate.com.Lung transplant: procedure and postoperateive management. 2008 Uptodate.com.

BacterialBacterial

Most common pathogen are those that Most common pathogen are those that colonized the donor or recipient.colonized the donor or recipient.

Gram neg such as Pseudomonas, Klebsiella Gram neg such as Pseudomonas, Klebsiella and H. flu are most common. Gram positives and H. flu are most common. Gram positives (staph) are also a frequent cause (head (staph) are also a frequent cause (head injury).injury).

Most centers use a 7-10 day prophylaxis (eg Most centers use a 7-10 day prophylaxis (eg vanco, cefepime) or depending on previous vanco, cefepime) or depending on previous colonization.colonization.

We use generally use ceftaz and clox till lines We use generally use ceftaz and clox till lines and drains are out. and drains are out.

ViralViral

CMV is most commonly seen infection post-CMV is most commonly seen infection post-op complication (13-75% of transplants).op complication (13-75% of transplants).

Most risk obviously in CMV neg recipient Most risk obviously in CMV neg recipient receiving CMV pos donor. receiving CMV pos donor.

Optimal prophylaxis remains controversial. Optimal prophylaxis remains controversial. Most centers will supply 12 weeks of IV Most centers will supply 12 weeks of IV

gancyclovir (5 mg/kg qd) for +D/-R and CMV gancyclovir (5 mg/kg qd) for +D/-R and CMV immunoglobulin.immunoglobulin.

If just +R get only gancyclovir for 12 weeks.If just +R get only gancyclovir for 12 weeks. If –D/-R nothing. If –D/-R nothing.

ViralViral

Patients in the community are also Patients in the community are also susceptible to other viral infections susceptible to other viral infections (eg. RSV, adenovirus, influenza, (eg. RSV, adenovirus, influenza, parainfluenza).parainfluenza).

Several of these have specific Several of these have specific treatments so be aware of them (eg. treatments so be aware of them (eg. Aerosolized ribavirin)Aerosolized ribavirin)

Fungal infectionsFungal infections Major problem in the long term.Major problem in the long term. Aspergillus and Candida account for Aspergillus and Candida account for

majority.majority. Both can represent colonization but also Both can represent colonization but also

can be life-threatening infections. can be life-threatening infections. Aspergillus colonization and infection Aspergillus colonization and infection

occur within first 6 months. occur within first 6 months. Mortality for pneumonia/disseminated Mortality for pneumonia/disseminated

disease approaches 60%.disease approaches 60%.Critical Care Aspects of Lung Transplantation. Journal of Intensive Care Med 19(2); 2004Critical Care Aspects of Lung Transplantation. Journal of Intensive Care Med 19(2); 2004

Fungal infectionsFungal infections

Several antifungal prophylactic strategies Several antifungal prophylactic strategies used.used.

Systemic or inhaled or both.Systemic or inhaled or both. However, use of systemic antifungal However, use of systemic antifungal

therapies limited by lack of in vitro therapies limited by lack of in vitro activity against some infections, drug activity against some infections, drug interactions, significant treatment interactions, significant treatment limiting toxicities.limiting toxicities.

Several reports of using inhaled Ampho B Several reports of using inhaled Ampho B lipid complex….may see used in future.lipid complex….may see used in future.


What do we do?What do we do? Candida prophylaxis= nystatin swish Candida prophylaxis= nystatin swish

and swallow.and swallow. PCP= septra or aerosolized PCP= septra or aerosolized

pentamidine.pentamidine. Aspergillus=aerosolized ampho B.Aspergillus=aerosolized ampho B. Toxoplasma neg px= pyrimethamine Toxoplasma neg px= pyrimethamine

for 6 months.for 6 months.


Although bronchial dehiscence is a rare Although bronchial dehiscence is a rare complication due to improved surgical tech complication due to improved surgical tech and lack of steroids for period of time after and lack of steroids for period of time after OR.OR.

B/c of inherent ischemia occurring at the B/c of inherent ischemia occurring at the anastomosis fungal infections my develop at anastomosis fungal infections my develop at this site.this site.

This can lead to life threatening airway This can lead to life threatening airway complicatoins.complicatoins.

Careful attention should be paid to this area Careful attention should be paid to this area on all bronchoscopies. on all bronchoscopies.

Fungal infectionsFungal infections In one study by Nunley it was found that 46.7% In one study by Nunley it was found that 46.7%

with anastamosis infections had airway with anastamosis infections had airway complications where in only 8.7% of patients complications where in only 8.7% of patients without. without.

These included bronchial stenosis, These included bronchial stenosis, bronchomalacia, fatal hemorrhage and bronchomalacia, fatal hemorrhage and dehiscence. dehiscence.

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


If on bronchoscopic inspection have If on bronchoscopic inspection have pseudomembranes should perform pseudomembranes should perform biopsy. biopsy.

Optimal treatment still unknown.Optimal treatment still unknown. Suggested expert opinion is that should Suggested expert opinion is that should

use combination of systemic and inhaled use combination of systemic and inhaled antifungal agents. (eg. Ampho B) antifungal agents. (eg. Ampho B)

May need bronchoscopic debridement May need bronchoscopic debridement of the tissue.of the tissue.


Treatment of systemic infections.Treatment of systemic infections. Albicans still fluconazol. Albicans still fluconazol. Non-albicans caspofungin. Non-albicans caspofungin. Ampho B is classic drug of choice for Ampho B is classic drug of choice for

aspergillus and fusarium. More aspergillus and fusarium. More utilization of Vori and caspo in last utilization of Vori and caspo in last several years.several years.

Careful with Vori as has extensive Careful with Vori as has extensive interactions with immunosuppressants. interactions with immunosuppressants.

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

CASECASE

The oxygen delivered via ECMO was The oxygen delivered via ECMO was adjusted according to the arterial blood adjusted according to the arterial blood gas results, and was successfully gas results, and was successfully reduced to 40% within 4 days. After the reduced to 40% within 4 days. After the first 48 hours, the ECMO flow rate was first 48 hours, the ECMO flow rate was maintained at 2.5 L/min, with 3200 maintained at 2.5 L/min, with 3200 RPM. Prior to discontinuation of ECMO, RPM. Prior to discontinuation of ECMO, the patient was relying on his lung for the patient was relying on his lung for oxygenation with no oxygen given oxygenation with no oxygen given through the oxygenator. through the oxygenator.

CASECASE

Both the cannulae were successfully removed Both the cannulae were successfully removed with application of pressure on the site and with application of pressure on the site and without any problems. The patient did very without any problems. The patient did very well there after and was discharged to the ward well there after and was discharged to the ward within 8 days. within 8 days.

While on the ward several surveillance While on the ward several surveillance bronchoscopies were performed. There were bronchoscopies were performed. There were some pseudomembrains seen near the some pseudomembrains seen near the anastomosis and they were sampled. They anastomosis and they were sampled. They were positive for candida sp. and treatment were positive for candida sp. and treatment initiated with IV caspofungin. The site looked initiated with IV caspofungin. The site looked stable during repeated bronchoscopy. stable during repeated bronchoscopy.

CASECASE

On day 15 you are called to the ward On day 15 you are called to the ward for respiratory decline. He is in for respiratory decline. He is in respiratory distress and a CXR is respiratory distress and a CXR is performed. performed.

CASECASE

What is high on your differential for What is high on your differential for the cause of the abnormality? the cause of the abnormality?

The patient requires reintubation, The patient requires reintubation, independent lung ventilation and is independent lung ventilation and is taken to the OR for repair of his taken to the OR for repair of his bronchial dehiscence. bronchial dehiscence.

Is there any evidence for the Is there any evidence for the outcomes of Lung transplant patients outcomes of Lung transplant patients who require readmission to the ICU?who require readmission to the ICU?

All lung transplants at Duke University Medical All lung transplants at Duke University Medical Center discharged from hosp between March 99 Center discharged from hosp between March 99 and Feb 01. and Feb 01.

51/214 px (23.8%) required ICU admissions. 51/214 px (23.8%) required ICU admissions. Of those 27/51 (57.5%) required MV. Of those 27/51 (57.5%) required MV. Dx:Dx: Resp failure (70%)Resp failure (70%) Sepsis (6.8%)Sepsis (6.8%) Pneumothorax, atrial fib, high-risk bronchoscopy, Pneumothorax, atrial fib, high-risk bronchoscopy,

PE, antibiotic desensitization and cardiac arrest PE, antibiotic desensitization and cardiac arrest (2.7% each) (2.7% each)

19/51 (37%) died during their ICU 19/51 (37%) died during their ICU admission.admission.

16/27 (59%) receiving MV died. 16/27 (59%) receiving MV died. Px who died had lower FEV1 to Px who died had lower FEV1 to

posttransplant best FEV1 ratio prior to posttransplant best FEV1 ratio prior to ICU admission. (51% vs 75% p=0.001)ICU admission. (51% vs 75% p=0.001)

Also, had higher APACHE III scores on Also, had higher APACHE III scores on ICU admission compared to survivors. ICU admission compared to survivors.

Survival rates by Kaplan-Meier:Survival rates by Kaplan-Meier: 1 year= 43.1%1 year= 43.1% 2 year= 40.9%2 year= 40.9%

Conclusions: Conclusions: ICU admission and mechanical ICU admission and mechanical

ventilation, is associated with a poor ventilation, is associated with a poor prognosis in lung transplant but….prognosis in lung transplant but….

Is appropriate for selected patients Is appropriate for selected patients with good allograft function.with good allograft function.

ConclusionsConclusions

More immediate ICU complications with More immediate ICU complications with IPAH and IPF. IPAH and IPF.

Beware the patient that required by-pass or Beware the patient that required by-pass or that did poorly on single lung ventilation. that did poorly on single lung ventilation.

If become shocky….act quickly and look for If become shocky….act quickly and look for the diagnosis. (? Bleeding, STAT TEE, the diagnosis. (? Bleeding, STAT TEE, contact surgeon)contact surgeon)

Reperfusion injury is a diagnosis of Reperfusion injury is a diagnosis of exclusion and may require independent exclusion and may require independent lung ventilation or ECMO.lung ventilation or ECMO.

ConclusionsConclusions Predictors of need for independent lung Predictors of need for independent lung

ventilation include preoperative airflow ventilation include preoperative airflow limitation (FVC1/FVC) and hyperinflation.limitation (FVC1/FVC) and hyperinflation.

Mobilize ECMO early.Mobilize ECMO early. If questioning diagnosis of acute rejection vs If questioning diagnosis of acute rejection vs

infection use open lung biopsy.infection use open lung biopsy. Acute rejection is a marker for future Acute rejection is a marker for future

BOS….we may be able to make a difference.BOS….we may be able to make a difference. Patients with post-op good allograft function Patients with post-op good allograft function

should be candidates for readmission to ICU.should be candidates for readmission to ICU.

Documents

Lung Transplant Dave Sweet. CASE You are currently the fellow working at VGH and as you come in Monday morning the charge nurse tells you that there are