ArticlePDF Available

Cardiopulmonary exercise testing for the selection of patients undergoing surgery for lung cancer: Friend or foe?

Cardiopulmonary exercise
testing for the selection of
patients undergoing surgery for
lung cancer: friend or foe?
Eric Lim,
Michael Beckles,
Chris Warburton,
David Baldwin
The contribution of exercise testing for
risk assessment for lung resection is well
established and has been embedded in
international guidelines from Europe
the USA.
There are many forms of exer-
cise tests (6 min walk, 12 min walk,
shuttle walk, stair climbing), but the most
established investigation is formal assess-
ment of maximum oxygen consumption
during exercise (VO
max). British and
American (American College of Chest
Physicians (ACCP)) guidelines use VO
max as the ultimate assessment of opera-
tive risk, positioned at or near the end of
the functional algorithm,
whereas Euro-
pean guidelines recommend the use of this
test much earlier in patients with a forced
expiratory volume in 1 s (FEV
) or carbon
monoxide transfer factor (TlCO)<80%
Numerous cohort studies and a meta-
analysis report the association of low VO
max and high risklung resection.
However highis not quantied and
riskis not dened, two fundamentally
important denitions if guidelines that
use these terms are to be applied clini-
cally. Here we focus on validity of the
max studies and the clinical utility of
the available evidence with respect to
individual interpretation of risk.
Arguably, the most important outcome
when considering surgery for lung cancer
is the ability to survive the procedure.
currently available evidence is the lack of
appropriately powered studies to address
specically dependent on sample size,
but rather the number of eventsdthat
is deathsdan uncommon outcome in
thoracic surgery. In the UK, lobectomy,
the most common procedure for lung
cancer, carried an operative mortality of
w2% in 2004e2005,
and in the USA the
mortality rate has been reported to range
from 2.3% to 4.1%.
Reective of this,
the largest study in this context on VO
What is clearly more disconcerting is that
publications for which recommendations
on estimation of operative mortality risk
have been based have sample sizes
ranging from 8 to 160.
Many studies have dened arbitrary cut-off
values ranging from 15 to 20/ml/kg/min as
asafecut-off value
because above
these levels no patient experienced an
adverse event. What is the validity of this
type of recommendation?
The answer lies in the uncertainly that
surrounds the observation of no events (ie,
upper 95% CI), a function of the sample
size. For a standard binomial distribution,
the upper limit of the CI of zero events
with the sample size of 8e160 corre-
sponds to 42e2.7%, respectively (gure 1),
illustrating high limits of uncertainty in
the majority of studies with smaller
sample sizes.
Given these limitations, are there any
other alternatives for the risk assessment
for operative morality?Thoracoscore is
a composite scoxring system that can be
used to quantify risk. It is a logistic
regression-derived model with coefcients
provided for individual risk factors, calcu-
lated to provide a percentage probability
of death. It is currently the best model and
was developed from a sample size of
15 183 patients with 338 deaths, and
provides excellent discrimination with an
area under the curve of 0.82.
more, it has been validated in different
Apart from superior statis-
tical power, much larger sample size,
external validity and excellent perfor-
mance, the logistic risk model carries two
further attractive advantages compared
with VO
max assessment: it is cost free
and can be universally available.
The consistent message that lower values
of Vo
max are associated with higher risk
of complications is to be expected as
a measure of cardiovascular tness. From
a patients and clinicians perspective,
however, the nature of the complications is
of central importance. All studies to date
have used composite end points and, when
multiple outcomes are combined, it
becomes difcult to interpret the impact of
each individual component. It has been
recommended that each outcome should
have a similar weighting or clinical impor-
tance to facilitate clinical interpretation.
For example, death and myocardial infarc-
tion would be combined to estimate the
total number of patients that may have
experienced a myocardial infarction and
survived, added to those that have
(presumably) experienced a myocardial
infarction and died.
Researchers, however, may use
composite outcomes to increase the power
of the study (by increasing event rate)
and therefore increasing the chances of
achieving statistically signicant results.
The corollary is that important outcomes
such as death can be piggybacked within
the pool of less important outcomes such
as atelectasis
57e911e14 16
or purulent
giving rise to considerable dif-
culties for the clinician and, more impor-
tantly, the patient to evaluate the
importance of the overall result. We
believe that most patients would not
consider readmission to the intensive
care unit,
57e911e14 16
or postoperative
68e10 13 16
as prohibitive
complications leading them to refuse
Imperial College and Academic Division of Thoracic
Surgery, The Royal Brompton Hospital, London, UK;
Department of Acute Medicine, The Royal Free
Hospital, London, UK;
Department of Respiratory
Medicine, Aintree Chest Centre, Liverpool, UK;
Respiratory Medicine Unit, David Evans Research
Centre, Nottingham University Hospitals, Nottingham,
Correspondence to Eric Lim, Academic Division of
Thoracic Surgery, Royal Brompton Hospital, Sydney
Street, London SW3 6NP, UK;
Thorax October 2010 Vol 65 No 10 847
Editorial on October 28, 2015 - Published by from
A clear explanation of risks and benets is
central to good consenting practice when
offering treatment options to our
patients. Dichotomous categorisation of
highand standardrisk using VO
for risk assessment, accompanied by
a combination of varied outcomes (some
of which have little inuence on patient
decision making) renders the information
difcult to apply in practice. The lack of
a numerical estimate leads to subjective
interpretation of high;moreover,many
studies do not document the uncertainty
(condence limits) that surround their
estimates. As there is no accepted level
of baseline risk, it is not possible to
quantify the relative magnitude of high
to facilitate the interpretation.
It is intuitive that clinicians seek to protect
the interests of their patients, and some
may wonder if a discussion of the quanti-
cation and interpretation of risk is rele-
vant as opposed to acceptance and
avoidance of risk based on published values.
In the CALGB 9238 study, the largest in the
series (with 422 patients), physicians were
allowed to offer surgical treatment of
patients with very high risk,dened as
<900 ml and VO
max of <15/ml/kg/
min. Of the 68 patients in the very high
riskgroup, there was only one post-
operative death within 30 days and a total
of three in-hospital deaths.
More impor-
tantly, on follow-up, the operated patients
in the very high risk group had more than
double the median survival compared with
the non-operated patients (36.0 months vs
15.8 months, p<0.001), illustrating accept-
able procedural mortality and morbidity
with twice the median survival with case
selection on parameters independent of VO
max. Denying patients with prohibitive
values of VO
max the opportunity to
consider surgery as a management option
may in fact be against their best interests.
As the study was not randomised, it is
important to bear in mind the invariable
presence of selection bias, and the possi-
bility that a better result was achieved by
offering surgery to tter patients with less
co-morbidity. Our point is more to ques-
tion the conventionallower limit of safety
and the results that can be achieved by
further selection.
We acknowledge the consistent message
that low levels of VO
max are associated
with increased complications from surgery.
However, we believe current recommen-
dations are awed by small sample sizes,
resulting in imprecise risk estimates.
Moreover, the lack of numerical quanti-
cation leads to difculties in dening the
level of acceptable risk. Furthermore, the
use of composite outcomes leads to a lack of
agreement on the importance of the risks,
and the incongruence limits the clinical
applicability to inform patients on the
decision to undergo surgery. We believe that
management options should be discussed
at a multidisciplinary level but decisions
should be undertaken at patient level. This
is because patients are heterogeneous, with
individual perceptions on the value of
benet and risk. As the lower limits of
safety remain imprecisely dened, patients
with multidisciplinary team-dened
prohibitivelevels of risk may not be
offered the opportunity to consider surgery
as an option and denied the possibility of
increased life expectancy.
There may also be a degree of concern if
postoperative quality of life may be a trade-
high risk cohort; however, prospective
studies indicated that patients traditionally
considered at higher risk of lung resection
had postoperative physical and emotional
quality of life scores similar to those
observed in younger and tter patients.
Before widespread use, further work
needs to be performed to determine if
cardiopulmonary exercise testing is an
independent predictor of mortality (eg,
above and beyond that of Thorascore), to
relate the study to individual outcomes that
would inuence the decision to undergo
surgery, to provide numerical quantication
of risk with an estimate of uncertainty and
to demonstrate validity in different cohorts.
Competing interests None.
Provenance and peer review Commissioned;
externally peer reviewed.
Published Online First 13 July 2010
Thorax 2010;65:847e849.
1. Brunelli A, Charloux A, Bolliger CT, et al. ERS/ESTS
clinical guidelines on fitness for radical therapy in lung
cancer patients (surgery and chemo-radiotherapy).
Eur Respir J 2009;34:17e41.
2. Colice GL, Shafazand S, Griffin JP, et al. Physiologic
evaluation of the patient with lung cancer being
considered for resectional surgery: ACCP evidenced-
based clinical practice guidelines (2nd edition).
Chest 2007;132(3 Suppl):161Se77S.
3. British Thoracic Society; Society of
Cardiothoracic Surgeons of Great Britain and
Ireland Working Party. BTS guidelines: guidelines
on the selection of patients with lung cancer for
surgery. Thorax 2001;56:89e108.
4. Bechard D, Wetstein L. Assessment of exercise
oxygen consumption as preoperative criterion for lung
resection. Ann Thorac Surg 1987;44:344e9.
5. Bolliger CT, Jordan P, Soler M, et al. Exercise
capacity as a predictor of postoperative
complications in lung resection candidates. Am J
Respir Crit Care Med 1995;151:1472e80.
6. Boysen PG, Clark CA, Block AJ. Graded exercise
testing and postthoracotomy complications.
J Cardiothorac Anesth 1990;4:68e72.
7. Brunelli A, Belardinelli R, Refai M, et al. Peak oxygen
consumption during cardiopulmonary exercise test
improves risk stratification in candidates to major
lung resection. Chest 2009;135:1260e7.
8. Brutsche MH, Spiliopoulos A, Bolliger CT, et al.
Exercise capacity and extent of resection as
predictors of surgical risk in lung cancer. Eur Respir J
9. Epstein SK, Faling LJ, Daly BD, et al. Predicting
complications after pulmonary resection. Preoperative
exercise testing vs a multifactorial cardiopulmonary
risk index. Chest 1993;104:694e700.
10. Richter Larsen K, Svendsen UG, Milman N, et al.
Exercise testing in the preoperative evaluation of
patients with bronchogenic carcinoma. Eur Respir J
11. Markos J, MullanBP,HillmanDR,et al. Preoperative
assessment as a predictorof mortalityand morbidityafter
lung resection. Am Rev Respir Dis 1989;139:902e10.
12. Morice RC, Peters EJ, Ryan MB, et al. Exercise
testing in the evaluation of patients at high risk for
complications from lung resection. Chest
13. Smith TP, Kinasewitz GT, Tucker WY, et al. Exercise
capacity as a predictor of post-thoracotomy
morbidity. Am Rev Respir Dis 1984;129:730e4.
14. Torchio R, Gulotta C, Parvis M, et al. Gas exchange
threshold as a predictor of severe postoperative
complications after lung resection in mild-to-
moderate chronic obstructive pulmonary disease.
Monaldi Arch Chest Dis 1998;53:127e33.
15. Villani F, Busia A. Preoperative evaluation of patients
submitted to pneumonectomy for lung carcinoma:
role of exercise testing. Tumori 2004;90:405e9.
16. Wang J, Olak J, Ultmann RE, et al. Assessment of
pulmonary complications after lung resection.
Ann Thorac Surg 1999;67:1444e7.
17. Loewen GM, Watson D, Kohman L, et al. Preoperative
exercise VO
measurement for lung resection
candidates: results of Cancer and Leukemia Group B
Protocol 9238. J Thorac Oncol 2007;2:619e25.
18. BobbioA, Chetta A, Internullo E, et al. Exercise capacity
assessmentin patientsundergoing lung resection. Eur J
Cardiothorac Surg 2009;35:419e22.
19. Page R, Keogh B. National Thoracic Surgery Activity
and Outcomes Report. Oxford; Dendrite Clinical
Systems Ltd, 2008.
Sample size (n)
Upper confidence limit (percentage)
Figure 1 Upper binomial confidence limit for
‘no observations’.
848 Thorax October 2010 Vol 65 No 10
Editorial on October 28, 2015 - Published by from
20. Schipper PH, Diggs BS, Ungerleider RM, et al. The
influence of surgeon specialty on outcomes in general
thoracic surgery: a national sample 1996 to 2005.
Ann Thorac Surg 2009;88:1566e72;discussion
21. Benzo R, Kelley GA, Recchi L, et al. Complications of
lung resection and exercise capacity: a meta-analysis.
Respir Med 2007;101:1790e7.
22. Falcoz PE, Conti M, Brouchet L, et al. The Thoracic
Surgery Scoring System (Thoracoscore): risk model
for in-hospital death in 15,183 patients requiring
thoracic surgery. J Thorac Cardiovasc Surg
23. Chamogeorgakis TP, Connery CP, Bhora F, et al.
Thoracoscore predicts midterm mortality in patients
undergoing thoracic surgery. J Thorac Cardiovasc
Surg 2007;134:883e7.
24. Montori VM, Permanyer-Miralda G, Ferreira-
Gonzalez I, et al. Validity of composite end points in
clinical trials. Br Med J 2005;330:594e6.
25. Lim E, Brown A, Helmy A, et al. Composite
outcomes in cardiovascular research: a survey of
randomized trials. Ann Intern Med
26. Brunelli A, Socci L, Refai M, et al. Quality of life
before and after major lung resection for lung cancer:
a prospective follow-up analysis. Ann Thorac Surg
Pseudomonas aeruginosa
infection in cystic fibrosis:
prevent, eradicate or both?
Ernst Eber, Maximilian S Zach
Lung disease in cystic brosis (CF) starts
early in life. Infection, inammation,
reduced lung function and abnormal chest
CT ndings are present in a signicant
proportion of infants with CF at a time
when many of these children have no clini-
cally apparent lung disease.
Infection and
inammation are intimately linked early in
the course of CF lung disease.
detection of airway inammation in the
absence of apparent infection led to the
speculation that CF is associated with an
intrinsic abnormality of immune regula-
However, more recent data argue
against a primary CF-associated dysregula-
tion of local immune function where
inammation might precede infection; they
rather support the central role of bacterial
pathogens in initiating and sustaining the
neutrophil-mediated airway inammation
characteristic of CF lung disease, with
ahigherinammatory burden in children
infected with Pseudomonas aeruginosa (PA)
than in those infected with organisms other
than PA or uninfected.
Chronic respi-
ratory infection is one of the main charac-
teristics of CF and signicantly contributes
to morbidity and mortality.
12 13
In young
children Staphylococcus aureus,Haemophilus
inuenzae and PA are the major lower airway
12 13
Chronic infection with PA is
known to be associated with a worse prog-
nosis in children, adolescents and adults,and
patients with mucoid PA strains do worse
than those with non-mucoid strains.
Thus, prevention or early detection and
treatment of infection, in particular with
PA, may prevent or delay irreversible lung
damage from inammation and conse-
quently may improve prognosis. In order to
prevent acquisition of PA, hygienic measures
to decontaminate environmental reservoirs
of this organism including medical equip-
ment have been stressed, and CF centres
have adopted meticulous microbiological
surveillance and effective segregation poli-
cies to limit cross-infection between
patients. Furthermore, several trials have
been undertaken to assess the value of
vaccination as a preventive strategy for PA
infection but, with the variable outcomes of
these trials, vaccines against PA cannot be
At present, early treatmen t
of initial infectiondthat is, an attempt to
eradicate PAdis the agreed standard.
Literature on antibiotic prophylaxis of PA
infection has so far remained scarce.
21 22
In this issue of Thorax, Tramper-
Stranders et al report on a randomised
controlled trial investigating the effec-
tiveness of cycled antibiotic prophylaxis in
children with CF (see page 915).
dren between 0 and 18 years of age
received 3-monthly 3-week treatments
with oral ciprooxacin and inhaled
colistin or placebo for 3 years. The authors
apparently chose this regimen because
many CF centres across Europe have used
the combination of oral ciprooxacin and
inhaled colistin as eradication therapy for
PA, going back to the rst randomised
controlled trial of an eradication regimen
almost 20 years ago.
Patients were
followed at 3-monthly intervals in
between treatment cycles and respiratory
specimens collected for microbiology
studies were either oropharyngeal cough
swabs or sputum samples (notably, the
vast majority of patients did not produce
sputum). In addition, serum samples were
collected every 6 months for measurement
of anti-Pseudomonas antibodies. Infection
with PA (the primary end point) was
dened as either two positive cultures
taken >1 week apart or one positive
culture and a severe pulmonary exacer-
bation. Nineteen out of 65 patients (29%)
reached the primary end point (in only 4
of them was PA detected in sputum);
information on how many strains were
mucoid or non-mucoid is not given.
Fourteen patients had positive antibody
titres during the study period once or
more often; 10 of them were culture-
positive before they were serology-posi-
tive. This study once more shows that
detection of infection in children with CF
is difcult. In general, young children are
not able to expectorate sputum, and
oropharyngeal cultures do not reliably
predict the presence of bacterial pathogens
in the lower airways of young children
with CF.
13 25
Thus, cultures from bron-
choalveolar lavage (BAL) uid are usually
taken as the gold standard for detection of
infection in the lower airways. However,
owing to sampling problems, even a nega-
tive BAL uid culture or the absence of
a particular organism on culture does not
guarantee that the organism is not present
in the lungs of the patient.
For this
reason, additional markers of infection are
desirable and the use of specic serum
antibodies against PA may be helpful in
dening the status of PA infection.
However, the majority of patients are
antibody-negative at the time of rst
infection so specic antibodies against PA
alone are not recommended to diagnose
early infection.
With oropharyngeal
cough swabs being the prevailing respira-
tory specimens, one might speculate that at
least some patients with positive upper
airway cultures might have had negative
Klinische Abteilung fu
¨r Pulmonologie und Allergologie,
Univ-Klinik fu
¨r Kinder- und Jugendheilkunde,
Medizinische Universita
¨t Graz, Graz, Austria
Correspondence to Dr Ernst Eber, Klinische Abteilung
¨r Pulmonologie und Allergologie, Univ-Klinik fu
¨r Kinder-
und Jugendheilkunde, Medizinische Universita
¨t Graz,
Auenbruggerplatz 34, 8036 Graz, Austria;
Thorax October 2010 Vol 65 No 10 849
Editorial on October 28, 2015 - Published by from
lung cancer: friend or foe?
selection of patients undergoing surgery for
Cardiopulmonary exercise testing for the
Eric Lim, Michael Beckles, Chris Warburton and David Baldwin
doi: 10.1136/thx.2009.133181
2010 65: 847-849 originally published online July 13, 2010Thorax
Updated information and services can be found at:
These include:
References #BIBL
This article cites 25 articles, 6 of which you can access for free at:
Email alerting box at the top right corner of the online article.
Receive free email alerts when new articles cite this article. Sign up in the
To request permissions go to:
To order reprints go to:
To subscribe to BMJ go to: on October 28, 2015 - Published by from
... For morbidity, preoperative CPEX testing has poor (19,24,25) to average (20) discriminatory accuracy to predict postoperative outcomes after cancer resection surgery, so has limited utility as an isolated preoperative screening tool. Furthermore, investigations often used composite outcomes and included low Clavien-Dindo graded complications (19,20,23), which reduces the clinical meaningfulness of associations found (40). Much research in CPEX testing has been a continuation of the seminal work of Older et al, in a paper published in 1993; reporting that AT may predict postoperative cardiac-related death after major surgery (7). ...
... Currently, there is no accepted definition of "prohibitive risk" for lung cancer therapy. 63 Assessments of health in patients in whom lung cancer has been newly diagnosed and in lung cancer survivors can help better define both prohibitive and relative risks by identifying long-term disabilities resulting from the associated treatments. Such assessments might be useful to riskstratify patients being considered for therapy, facilitate postoperative/treatment care, and potentially improve outcomes and QoL. ...
The harms associated with lung cancer treatment include perioperative morbidity and mortality and therapy-induced toxicities on various organs, including the heart and lungs. Optimal treatment, therefore, entails a need for risk-assessment to weigh the probabilities of benefits versus harms. Exercise testing offers an opportunity to evaluate a patient’s physical fitness/exercise capacity objectively. In lung cancer, it is most often used to risk-stratify patients undergoing evaluation for lung cancer resection surgery. In recent years, its use outside of this context has been described, including in non-surgical candidates and lung cancer survivors. In this article we review the physiology of exercise testing and lung cancer. Then, we assess the utility of exercise testing in lung cancer patients in 4 contexts (preoperative evaluation for lung cancer resection surgery, following lung cancer surgery, lung cancer prognosis, and assessment of efficiency of exercise training programs) after systematically identifying original studies involving the most common forms of exercise tests in this patient population: laboratory cardiopulmonary exercise testing and simple field testing with the six-minute walk test, shuttle walk test, and/or stair climbing test. Lastly, we propose a conceptual framework for risk-assessment of lung cancer patients being considered for therapy and identify areas of further studies in this patient population.
... While a simple principle, respiratory literature (especially on exercise testing) is littered with studies that use combined outcomes with several end points (e.g. death, pneumonia and arrhythmia), which complicates interpretation [30]. The CALGB 9238 trial was a prospective multicentre study to validate the use of primary exercise VO 2 measurement for the prediction of surgical risk [31]. ...
Full-text available
To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines in advanced disease, early stage disease and locally-advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on early stage disease.
... Functional assessment includes a walk test and cardiopulmonary exercise testing. Surgeons need to bear in mind though that these tests do have shortcomings and in recognition of this, Lim et al. have proposed greater involvement of the patient in the decision making process (13,27). ...
Lung cancer is a leading cause of cancer related mortality. The role of surgery continues to evolve and in the last ten years there have been a number of significant changes in the surgical management of lung cancer. These changes extend across the entire surgical spectrum of lung cancer management including diagnosis, staging, treatment and pathology. Positron Emission Tomography (PET) scanning and ultrasound (EBUS) have redefined traditional staging paradigms, and surgical techniques, including video-assisted thoracoscopy (VATS), robotic surgery and uniportal surgery, are now accepted as standard of care in many centers. The changing pathology of lung cancer, with more peripheral tumours and an increase in adenocarcinomas has important implications for the Thoracic surgeon. Screening, using Low-Dose CT scanning, is having an impact, with not only a higher percentage of lower stage cancers detected, but also redefining the role of sublobar resection. The incidence of pneumonectomy has reduced as have the rates of "exploratory thoracotomy". In general, lung resection is considered for stage I and II patients with a selected role in more advanced stage disease as part of a multimodality approach. This paper will look at these issues and how they impact on Thoracic Surgical practice in 2013 and beyond.
... Indeed, CPEX testing has recently become part of routine medical surveillance of these patients in our center. In other disease settings, impaired CPEX performance is associated with a higher perioperative surgical risk, 5,6 but the association between baseline peak oxygen uptake and surgical risk has not been explored to date in a large cohort of adults with previous repair of tetralogy of Fallot (rTOF) undergoing PVR. ...
Indications for surgical pulmonary valve replacement (PVR) after repair of tetralogy of Fallot (rTOF) have recently been broadened to include asymptomatic patients. The outcome of PVR in adults after rTOF at a single tertiary centre was retrospectively studied. Preoperative cardiopulmonary exercise (CPEX) testing was included. Mortality was the primary outcome measure. Two-hundred-and-twenty-one PVRs were performed in 220 patients (130 male, median age 32, range 16-64 years). Homografts were used in 117, xenografts in 103 and a mechanical valve in 1 case. Early (30-day) mortality was 2%. Overall survival was 97% at one year, 96% at 3 years and 92% at 10 years. Survival after PVR in the later era (2005-2010;n=156) was significantly better compared to survival in the earlier era (1993-2004;n=65), [99% versus 94% at 1 year and 98% versus 92% at 3 years, respectively,P=0.019]. Earlier era patients were more symptomatic preoperatively (P=0.036) with a lower preoperative peak oxygen consumption (peak VO2,P<0.001). Freedom from redo surgical or transcatheter PVR was 98% at 5 years, and 96% at 10 years for the whole cohort. Peak VO2, VE/VCO2 slope and heart rate reserve during CPEX testing predicted risk of early mortality when analyzed with logistic regression analysis; peak VO2 emerged as the strongest predictor amongst them on multivariable analysis (Odds ratio 0.65 per ml/kg/min,P=0.041). PVR after rTOF has a low and improving mortality, with low need for re-intervention. Preoperative cardiopulmonary exercise testing predicts surgical outcome and should therefore be included in the routine assessment of these patients.
Objective(s) Patients undergoing lung resection are at risk of peri-operative complications, many of which necessitate unplanned critical care unit admission in the post-operative period. We sought to characterise this population, providing an up-to-date estimate of the incidence of unplanned critical care admission, and to assess critical care and hospital stay, resource use, mortality, and outcomes. Methods A multicentre retrospective cohort study of patients undergoing lung resection in participating UK hospitals over two years. A comprehensive dataset was recorded for each critical care admission (defined as the need for intubation and mechanical ventilation and/or renal replacement therapy), in addition to a simplified dataset in all patients undergoing lung resection during the study period. Multivariable regression analysis was used to identify factors independently associated with critical care outcome. Results A total of 11,208 patients underwent lung resection in 16 collaborating centres during the study period, and 253 patients (2.3%) required unplanned critical care admission with a median duration of stay of 13 (4-28) days. The predominant indication for admission was respiratory failure (68.1%) with 77.8% of patients admitted during the first 7-days following surgery. Eighty-seven (34.4%) died in critical care. On multivariable regression, only the diagnosis of right ventricular dysfunction and the need for both mechanical ventilation and renal replacement therapy were independently associated with critical care survival; this model however had poor predictive value. Conclusions Though resource intensive and subject to prolonged stay, following unplanned admission to critical care after lung resection outcomes are good for many patients; 65.6% of patients survived to hospital discharge and 62.7% were discharged to their own home.
Cardiopulmonary exercise testing (CPET) permits measurement of oxygen uptake (Vo2), an indicator of overall cardiopulmonary fitness and a useful measurement in the assessment of operative risk for lung cancer patients. The evidence supporting the use of CPET in pre-operative assessment of the lung cancer surgery patient is examined. CPET methodology and limitations, as well as alternatives to CPET for risk assessment are discussed.
In the decade since the last Lancet Seminar on lung cancer there have been advances in many aspects of the classification, diagnosis, and treatment of non-small-cell lung cancer (NSCLC). An international panel of experts has been brought together to focus on changes in the epidemiology and pathological classification of NSCLC, the role of CT screening and other techniques that could allow earlier diagnosis and more effective treatment of the disease, and the recently introduced seventh edition of the TNM classification and its relation to other prognostic factors such as biological markers. We also describe advances in treatment that have seen the introduction of a new generation of chemotherapy agents, a proven advantage to adjuvant chemotherapy after complete resection for specific stage groups, new techniques for the planning and administration of radiotherapy, and new surgical approaches to assess and reduce the risks of surgical treatment.
Full-text available
Composite end points are common in clinical trials. To describe how composite outcomes are used, constructed, and reported in cardiovascular trials and to evaluate the contribution of individual end points to the composite estimate of effect in those trials. Review of 2-group, parallel-design, randomized cardiovascular trials that used composite end points and were published in 14 clinical journals from 1 January 2000 to 1 January 2007. Published randomized trials in cardiovascular medicine and surgery. Two-group, parallel-design trials published in 14 leading general medical, cardiology, and cardiothoracic surgery journals from 1 January 2000 to 1 January 2007. The types and numbers of individual events included in the composite outcome and P values and risk estimates for the composite outcome. Of 304 trials published that used composite outcomes, 221 (73%) reported a composite primary outcome and 83 (27%) reported a composite secondary outcome. Composite outcomes comprised a median of 3 (interquartile range, 3 to 4) individual outcomes; death was the most common individual outcome. The total number of individual events and the total number of events represented by the composite outcome differed in 79% of trials. P values for composite outcomes were less than 0.050 more frequently than they were 0.050 or greater. Death as an individual end point made a relatively minimal contribution to estimates of effect summarized by the trials' composite end points, whereas revascularization made a greater contribution. All-cause and cardiovascular mortality were not distinguished, and the findings might not apply to trials in other fields. Composite outcomes in cardiovascular trials are frequent and commonly comprise 3 to 4 individual end points that vary in clinical significance. Discrepancies between the total number of individual events in a trial and those reported for composite outcomes are common. Individual outcomes do not contribute equally to composite measures, so the overall estimate of effect for a composite measure cannot be assumed to apply equally to each of its individual outcomes.
Although severe impairment on routine pulmonary function tests will identify patients with a high post-thoracotomy morbidity, cardiopulmonary complications often develop in patients with only a mild-to-moderate impairment in pulmonary function. To determine whether the preoperative exercise capacity can prospectively identify those at risk of developing complications, 22 patients scheduled for thoracotomy (mean age, 55.7 +/- 2 yr) underwent an incremental exercise test on a cycle ergometer to determine their maximal O2 uptake (VO2max) prior to thoracotomy. Routine pulmonary function tests were performed and postoperative forced expiratory volume in one second (FEV1) was predicted from split function perfusion lung scan in all subjects. Eleven of the 22 patients had no cardiopulmonary complications postoperatively. The age, history of prior cardiovascular disease, degree of impairment on routine pulmonary function tests, and predicted postoperative FEV1 were similar in those who did and those who did not experience complications. However, those without complications had a significantly higher VO2max than did those who experienced complications (22.4 +/- 1.4 versus 14.9 +/- 0.9 ml/kg/min, p less than 0.001). Only 1 of 10 patients with a VO2max greater than 20 ml/kg/min had a complication, whereas all 6 patients with a VO2max less than 15 ml/kg/min had a complication. We conclude that exercise testing is a useful adjunct in the evaluation of operative risk for thoracotomy.
While general thoracic surgical procedures are performed by several different surgical subspecialties, debate remains as to whether surgeon specialty impacts outcomes. The Nationwide Inpatient Sample (NIS) was queried for procedure codes for pneumonectomy, lobectomy, limited lung resection, and decortication. We constructed multivariate logistic regression models to calculate odds of hospital mortality or length-of-stay (LOS) greater than 14 days (a marker of morbidity), adjusted for age, sex, patient comorbidities, hospital setting, and surgeon specialty. A surgeon was considered general thoracic if they performed greater than 75% general thoracic operations and less than 10% cardiac operations, Cardiac if greater than 10% cardiac operations, and general surgeon if less than 75% general thoracic and less than 10% cardiac operations. A second set of models additionally adjusted for procedure-specific hospital and surgeon volume. From 1996 to 2005, the NIS estimates 41,808 pneumonectomies, 321,767 lobectomies, 75,200 limited lung resections, and 149,318 decortications were performed in the United States. For all procedures studied, general thoracic surgeons had significantly decreased odds-of-death and LOS greater than 14 days compared with general surgeons. Cardiac surgeons had significantly decreased LOS greater than 14 days for all operations and decreased odds-of-death for decortications, lobectomy, and limited lung resection compared with general surgeons. When further adjusted for surgeon volume, most differences in odds-of-death were no longer present; however, significantly decreased LOS greater than 14 days largely persisted for both general thoracic and cardiac surgeons. The majority of general thoracic surgical operations in the United States are performed by surgeons not specializing in thoracic surgery. Both general thoracic surgeons and cardiac surgeons achieve better outcomes than general surgeons. Differences in mortality may be more dependent on surgeon volume than subspecialty. Differences in morbidity are significantly impacted by surgeon specialty and volume.
A collaboration of multidisciplinary experts on the functional evaluation of lung cancer patients has been facilitated by the European Respiratory Society (ERS) and the European Society of Thoracic Surgery (ESTS), in order to draw up recommendations and provide clinicians with clear, up-to-date guidelines on fitness for surgery and chemo-radiotherapy. The subject was divided into different topics, which were then assigned to at least two experts. The authors searched the literature according to their own strategies, with no central literature review being performed. The draft reports written by the experts on each topic were reviewed, discussed and voted on by the entire expert panel. The evidence supporting each recommendation was summarised, and graded as described by the Scottish Intercollegiate Guidelines Network Grading Review Group. Clinical practice guidelines were generated and finalized in a functional algorithm for risk stratification of the lung resection candidates, emphasising cardiological evaluation, forced expiratory volume in 1 s, systematic carbon monoxide lung diffusion capacity and exercise testing. Contrary to lung resection, for which the scientific evidences are more robust, we were unable to recommend any specific test, cut-off value, or algorithm before chemo-radiotherapy due to the lack of data. We recommend that lung cancer patients should be managed in specialised settings by multidisciplinary teams.
The value is examined of preoperative functional assessment, including exercise capacity measurement by a cycloergometric maximal exercise test, in the prediction of postoperative cardio-pulmonary complication after lobar resection. In a prospective study over a 3-year period, all patients who were candidates for lung resection underwent preoperative functional evaluation by means of resting pulmonary function tests, measurement of the lung diffusing capacity for carbon monoxide and cardio-pulmonary exercise test. Patients who had had pneumonectomy or less than anatomical segmentectomy were excluded. The study population consisted of 73 patients. The postoperative morbidity and mortality record was collected. Sixty-four patients underwent lobectomy, five bilobectomy and four segmentectomy. Indication for surgery was NSCLC in 71 cases. Two postoperative deaths were recorded (2.7%). A pulmonary (n=19) and/or cardiac (n=17) complication was scored in 30 patients (41%). Mean preoperative FEV(1) and VO(2)max of patients who developed pulmonary complications were significantly lower (p=0.013 and p=0.043 respectively) than those of patients without pulmonary complications. Logistic regression analysis found FEV(1) to be an independent factor in pulmonary complication (p=0.002). With regard to pulmonary complication occurrence, the receiver operating characteristic curve showed an area of 0.69 with VO(2)max expressed in ml/kg min and of 0.62 when VO(2)max was expressed as a percentage of the predicted value. The widest point of the curve was found at a VO(2)max value of 18.7 ml/kg min. Six out of the 14 patients (43%) with a preoperative VO(2)max equal to or lower than 15 ml/kg min had a pulmonary complication. No functional preoperative identifiers were found for the 16 patients who presented with postoperative new onset atrial fibrillation. The mean preoperative value of carbon monoxide lung diffusing capacity was significantly lower (p=0.037) in the 30 patients who had postoperative cardio-pulmonary complications than in the complication-free population. Preoperative exercise capacity assessment helps in stratifying patients at risk for postoperative pulmonary complication. However, it does not appear to be an independent prognostic factor for postoperative outcome.
The objective of this investigation was to assess the association of peak oxygen consumption (Vo(2)) with postoperative outcome in a prospective cohort of patients undergoing major lung resection for the treatment of lung cancer. Preoperative symptom-limited cardiopulmonary exercise testing (CPET) performed using cycle ergometry was conducted in 204 consecutive patients who had undergone pulmonary lobectomy or pneumonectomy. Peak Vo(2) was tested for possible association with postoperative cardiopulmonary complications and mortality. Logistic regression analysis, validated by a bootstrap analysis, was used to adjust for the effect of other perioperative factors. The role of peak Vo(2) in stratifying the surgical risk was further assessed in different groups of patients subdivided according to their cardiorespiratory status. Logistic regression showed that peak Vo(2) was an independent and reliable predictor of pulmonary complications (p = 0.04). All six deaths occurred in patients with a peak Vo(2) of < 20 mL/kg/min (four deaths in patients with a peak Vo(2) of < 12 mL/kg/min). The mortality rate in this high-risk group was 10-fold higher (4 of 30 patients; 13%) compared to those with higher peak Vo(2) (p = 0.006). Compared to patients with a peak Vo(2) of > 20 mL/kg/min, those with a peak Vo(2) of < 12 mL/kg/min had 5-fold, 8-fold, 5-fold, and 13-fold higher rates, respectively, of total cardiopulmonary complications pulmonary complications, cardiac complications, and mortality. The present study supports a more liberal use of CPET before lung resection compared to the current guidelines since this test can help in stratifying the surgical risk and optimizing perioperative care.
Exercise testing was performed on 37 patients with resectable lung lesions who were deemed inoperable because of any of the following risk factors: (1) FEV1 less than or equal to 40 percent of predicted; (2) radionuclide calculated postlobectomy FEV1 less than or equal to 33 percent of predicted; or (3) arterial PCO2 greater than or equal to 45 mm Hg. The patients who reached a peak level of oxygen consumption during exercise (VO2Peak) of greater than or equal to 15 ml/kg/min were offered surgical treatment. Patients with a VO2Peak of less than 15 ml/kg/min were referred for nonsurgical management and excluded from the study. Eight patients underwent lung resection. Their pulmonary function revealed a severe obstructive lung defect with a group mean predicted FEV1 of 40 +/- 6 percent, an FEV1/FVC ratio of 47 +/- 10, a radionuclide calculated postlobectomy FEV1 of 31 +/- 4 percent, and a mean arterial PCO2 of 44 +/- 6 mm Hg. No relationship was found between each patient's exercise performance and spirometric function. Six of the patients had an uncomplicated postoperative course. Two patients had complications but no patient died as a result of surgery or postoperative complications. All patients were discharged from the hospital within 22 days (mean = 9.8 days). We conclude that exercise testing is a useful complement to conventional cardiopulmonary evaluation used in selecting patients for lung resection.
A controversy exists over whether or not preoperative exercise testing can predict postthoracotomy complications. This study was designed to evaluate the usefulness of a presurgical exercise protocol in patients with lung disease, but no evidence of cardiac disease. Seventy patients underwent baseline pulmonary function testing and split function perfusion studies, when indicated, to calculate predicted postoperative pulmonary function. Noninvasive data were incrementally collected from 17 patients by using a treadmill exercise tolerance test that was designed to elicit maximal performance. Inhaled and exhaled gas flow and volume, the partial pressure of O2 and CO2, maximal O2 consumption (VO2max), and maximal minute ventilation (VE max) were measured. The breathing and heart rate reserves were calculated by standard formulae in an attempt to separate cardiac from pulmonary exercise limitation. Two patients had postoperative cardiopulmonary complications after thoracotomy and lung resection, and six patients had noncardiopulmonary complications. There was no significant prognostic relationship among VO2max, VE max, maximum O2 pulse, and the incidence of postoperative cardiopulmonary complications. The percentages of predicted VE max and predicted maximum heart rate were related to the occurrence of total complications, but not specifically to cardiopulmonary complications. The results emphasize the difficulty in attempting to exercise thoracotomy candidates with chronic lung disease to maximal performance. Excluding patients from further surgical consideration because of exercise limitation is not feasible based on these data.
To refine the functional guidelines for operability for lung resection, we prospectively studied 55 consecutive patients with suspected lung malignancy thought to be surgically resectable. Lung function and exercise capacity were measured preoperatively and at 3 and 12 months postoperatively. Preoperative pulmonary scintigraphy was used to calculate the contribution to overall function by the affected lung or lobe and to predict postoperative lung function. Pneumonectomy was performed in 18 patients, lobectomy in 29, and thoracotomy without resection in six. No surgery was attempted in two patients who were considered functionally inoperable. Cardiopulmonary complications developed in 16 patients within 30 days of surgery, including three deaths. The predictions of postoperative function correlated well with the measured values at 3 months. For FEV1, r = 0.51 in pneumonectomy (p less than 0.05) and 0.89 in lobectomy (p less than 0.001). Predicted postoperative FEV1 (FEV1-ppo), diffusing capacity (DLCO), predicted postoperative DLCO (DLCO-ppo) and exercise-induced arterial O2 desaturation (delta SaO2) were predictive of postoperative complications including death and respiratory failure. In patients who underwent pneumonectomy, the best predictor of death was FEV1-ppo. The predictions were enhanced by expressing the value as a percentage of the predicted normal value (% pred) rather than in absolute units. For the entire surgical group a FEV1-ppo greater than or equal to 40% pred was associated with no postoperative mortality (n = 47), whereas a value less than 40% pred was associated with a 50% mortality (n = 6), suggesting that resection is feasible when FEV1-ppo is greater than or equal to 40% pred.(ABSTRACT TRUNCATED AT 250 WORDS)