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Rcsann 2016 0048
Rcsann 2016 0048
1
Cambridge University Hospitals NHS Foundation Trust, UK
2
University of Cambridge, UK
ABSTRACT
INTRODUCTION Frailty is becoming increasingly prevalent in the elderly population although a lack of consensus regarding a
clinical definition hampers comparison of clinical studies. More elderly patients are being assessed for surgical intervention but
the effect of frailty on surgical related outcomes is still not clear.
METHODS A systematic literature search for studies prospectively reporting frailty and postoperative outcomes in patients
undergoing surgical intervention was performed with data collated from a total of 12 studies. Random effects meta-analysis
modelling was undertaken to estimate the association between frailty and mortality rates (in-hospital and one-year), length of
hospital stay and the need for step-down care for further rehabilitation/nursing home placement.
RESULTS Frailty was associated with a higher in-hospital mortality rate (pooled odds ratio [OR]: 2.77, 95% confidence interval
[CI]: 1.62–4.73), a higher one-year mortality rate (pooled OR: 1.99, 95% CI: 1.49–2.66), a longer hospital stay (pooled mean
difference: 1.05 days, 95% CI: 0.02–2.07 days) and a higher discharge rate to further rehabilitation/step-down care (pooled
OR: 5.71, 95% CI: 3.41–9.55).
CONCLUSIONS The presence of frailty in patients undergoing surgical intervention is associated with poorer outcomes with
regard to mortality and return to independence. Further in-depth studies are required to identify factors that can be optimised
to reduce the burden of frailty in surgical patients.
KEYWORDS
Frailty – Elderly – Postoperative outcomes – Mortality rates – Sarcopenia
Accepted 28 June 2015
CORRESPONDENCE TO
Patrick Coughlin, E: [email protected]
The aging population alongside technological advances in is essential to first determine what effect frailty has on the
surgical and anaesthetic techniques present surgeons with outcomes of commonly performed surgical procedures. The
increasing dilemmas as to whether to intervene on elderly aim of this study was to estimate the association between
patients with a number of surgical conditions in both the frailty and adverse patient events in surgical patients using
elective and emergency setting.1,2 It is well recognised that meta-analysis.
age is a predictor of poorer postoperative outcomes, which
in turn predict poor long-term survival.3,4 Nevertheless, not
all older patients have poor surgical outcomes. The con-
Methods
cept of frailty is a recognised syndrome in the field of eld- An electronic search was undertaken using the PubMed and
erly medicine (although there is little consensus on its MEDLINE® databases from 1 January 1980 to 1 October
exact definition),5,6 and there is recognition of an overlap 2012. The search employed the terms ‘frailty’ and ‘sarcope-
between frailty and other geriatric syndromes including nia’ combined with the terms ‘surgery’, ‘postoperative’ and
sarcopenia.7,8 This lack of definition has resulted in a lack ‘hospital discharge’. Abstracts of the citations identified by
of consensus on the optimal method to determine frailty.9 the search were scrutinised by two of the authors (KO and
Not all elderly patients have a frailty phenotype, which RN) to determine eligibility for inclusion in the analysis.
suggests that frailty is not an inevitable consequence of Studies were deemed eligible if they were purely prospective
aging and as such, may be amenable to treatment. The studies, included surgically related outcomes (specifically
presence of a frailty phenotype has potential significance mortality rates, complication rates, length of stay [LOS] and
in an elderly surgical population as perioperative frailty need for postoperative placement in rehabilitation facilities)
related interventions may improve outcomes. However, it and reported on at least 50 patients.
There is no widely accepted definition of frailty. Scores severely and moderately frail data to provide frail outcome
relating to functional or cognitive dependence, weight, data. This decision was made prior to performing the stat-
muscle mass and co-morbid illness have been developed9 istical analyses that follow.
but these have not been widely adopted or standardised. It In two studies, a single patient in the group of patients
is therefore not yet possible to capture a frail population defined as being frail died.20,22 These single deaths are not
using one discrete definition. As a consequence, studies included in the in-hospital mortality meta-analysis because
were eligible if they defined frailty objectively and had a the zero counts in the corresponding non-frail group would
comparator ‘non-frail’ group. Patients undergoing all forms require artificial correction to include them in the random
of surgery (elective and emergency) except surgery for effects meta-analysis and the resulting normal approxima-
fractured neck of femur were included. Fractured neck of tion would be especially crude and could result in bias,
femur patients were excluded as the widespread involve- especially for relatively small studies such as these.
ment of orthogeriatricians could bias the comparability of The study by Makary et al provided mean lengths of hos-
these patients. Further references were found through pital stay but did not report the associated standard devia-
scrutinised review of the bibliographies of selected articles tions.21 This information is needed for the calculation of
to identify any articles missed by the searches. the within-study variance of the mean difference. As a
Outcomes of the meta-analysis were 1-year mortality result, the data for LOS from this study were not used. The
and early mortality (ie in-hospital mortality). For studies 2011 study by Peng et al provided data on LOS stratified by
where in-hospital mortality was not reported, 30-day sex.17 The pooled (across the two sexes) standard devia-
mortality or mortality ‘following surgery’ were used. Other tions for this study were therefore used to calculate the
outcome measures assessed were LOS and requirement corresponding within-study variance.
for step-down rehabilitation placement. Overall and organ The results from the meta-analyses are presented as
specific complication rates, where reported, are also sum- pooled ORs (with 95% confidence intervals [CIs]) for in-
marised in this review. hospital mortality, one-year mortality and the requirement
for step-down rehabilitation. The pooled mean difference
Statistical analysis (with 95% CI) is presented for the LOS. I2 statistics are
All analyses were performed using the random effects also presented to describe the extent of the between-study
model for meta-analysis, employing the DerSimonian and heterogeneity. Other postoperative complications were
Laird method.10 The meta-analyses of binary outcomes investigated qualitatively.
(in-hospital and one-year mortality, need for rehabilitation)
used study specific log odds ratios (comparing frail with
non-frail patients) as outcome data, and the resulting
Results
pooled estimates and confidence intervals were converted A total of 385 potentially relevant articles were identified
to odds ratios (ORs). Since the binary outcomes were all (Fig 1), of which 12 met the inclusion requirements for our
adverse events, a positive OR indicated that frailty is asso- systematic review, corresponding to a total of 7,960 patients
ciated with worse patient outcomes. The LOS meta-analy- (Table 1). Of the 7,300 patients for whom sex was reported,
sis used study specific mean differences of LOS as outcome 5,392 were men (73.9%). Of the twelve studies, one
data, where a positive mean difference indicated that frailty assessed patients undergoing elective non-cardiac surgery,
is associated with longer hospital stays. four assessed patients undergoing cardiac surgery, six
All analyses used numerical values (eg percentages, assessed patients undergoing gastrointestinal/hepatopan-
counts, means) reported by the studies. In some circum- creaticobiliary surgery and one assessed patients under-
stances, further calculations were needed to ascertain the going open abdominal aortic aneurysm surgery (Table 1).
outcome data but no values were obtained by attempting to The objective measures of frailty used in each study are
read them from graphs. Twelve studies were deemed suit- documented in Table 1.
able for meta-analysis. Six studies provided outcome data
for two distinct groups of patient groups (‘frail’ and ‘non- In-hospital/one-year mortality
frail’ groups).11–16 One study provided outcome data for In-hospital 30-day mortality was reported in 6 studies
four groups but identified one of these groups as patients (Table 2).13–18 The pooled OR for the association between
with sarcopenia;17 this group was used for frail data. The frailty and in-hospital mortality was 2.77 (95% CI: 1.62–
other five studies provided data for multiple patient groups 4.73, I2=16%). One-year mortality rates were reported in
and did not define a threshold to indicate frailty.18–22 five studies.11,13,17–19 The pooled OR for the association
With the exception of the study by Sündermann et al,18 between frailty and one-year mortality was 1.99 (95% CI:
data from the frailest group of patients provided our frail 1.49–2.66, I2=0%).
outcome data and the other groups were combined to pro-
vide our non-frail outcome data. However, as the most frail Length of stay
group (‘severely frail’) in the study by Sündermann et al Data for LOS were available in four studies.12,13,17,22 The
contained only 19 patients (9%) and also because the next pooled mean difference between the LOS for frail and non-
most frail group consisted of 95 clearly frail (‘moderately frail patients was 1.05 days (95% CI: 0.02–2.07 days,
frail’) patients (45%), it was decided to combine the I2=21%).
Table 1 Study characteristics including methods of determining frailty, sex and details of surgical procedures in the 12 studies
used in the systematic review
CT = computed tomography; TPA = total psoas area; ADL = activities of daily living; CABG = coronary artery bypass graft;
AAA = abdominal aortic aneurysm
*The Edmonton frail scale incorporates the domains of cognition, general health status, functional independence, social support,
medication use, nutrition, mood, continence and functional performance, and is scored out of 17.
Frailty itself can be theoretically defined as a clinically review were heterogeneous in their study populations and
recognisable syndrome of increased vulnerability as well definition of frailty but the effect of frailty (particularly on
as age associated decline in reserve and function.25 In clin- in-hospital and one-year mortality) was consistent.
ical practice, there is a lack of a standard definition26 and The biological basis for the effect of frailty is yet to be
this is reflected by the varying definitions of frailty used by fully understood, and may include changes at a cellular
the studies identified in this review. Fried et al defined level (eg oxidative damage) and systemic changes associ-
frailty as meeting three of five phenotypic criteria indicat- ated with medical co-morbidities.23,28,29 Cumulative co-
ing compromised physicality (eg slowed walking speed).25 morbidity may lead to poor outcome as patients may
Peng et al diagnosed frailty as loss of psoas muscle mass develop complications directly related to their medical con-
on diagnostic imaging.17 A 2013 publication focusing on dition or they may simply have reduced physiological
determining a definition did not reach consensus.27 reserve.
Although the precise definition of frailty is yet to be Separating frailty from specific co-morbidities or disabil-
determined, the concept that it leads to poor outcome fol- ity is difficult, especially as many of the frailty scores incor-
lowing surgery still stands. The studies included in this porate co-morbid illness. In this review, there were too few
Table 2 In-hospital and one-year mortality rates for frail and non-frail populations from the eight studies that reported mortality
as an outcome
AUC = area under the curve; CI = confidence interval; CRP = C-reactive protein
studies available and no patient specific data to attempt to fit applicable in clinical practice needs to be formulated and
meta-regression models, which can adjust for confounders in research to determine this must be undertaken. It is also
a very limited way. As such, from a statistical perspective, in essential to ascertain which specific aspects of the frailty
the absence of randomisation, it is not possible to infer causa- phenotype bring about such poor outcomes. This may dif-
tion from the analyses. However, the strength of the measures fer depending on the specific surgical population and path-
of association, combined with the fact that patient frailty is ology operated on, and it is the key to establishing how
such an obvious potential cause of adverse events, suggests best to improve frailty in surgical patients. Irreversible
that frailty is likely to be a strong predictor of poorer out- frailty should be taken into account when deciding
comes for all interventions despite these limitations. whether to proceed to surgical intervention and this may
A further statistical issue is that the in-hospital mortality improve the process of informed consent. Conversely, the
rates were generally quite low, which reduces the accuracy identification of potentially reversible components of frailty
of the normal approximations used in the corresponding not only provides an opportunity for surgical optimisation
meta-analysis. When determining longer-term mortality but also has wider benefits, particularly in terms of social
rates, the possibility of dropout needs to be considered. For and health economic planning.
studies that provided mortality rates at one year, dropout
rates were ignored when calculating study specific log
odds ratios and for studies that gave numbers at risk at
Acknowledgements
one year, an assumption was made that all those no longer DJ and LC are funded by Medical Research Council grants
at risk had died, which again ignores the possibility of U1052 60558 and G0800860.
dropout. Given that the follow-up period was only one year
and that only prospective studies were analysed, dropout is
likely to be small. References
1. Goldstein LJ, Halpern JA, Rezayat C et al. Endovascular aneurysm repair in
There was variation between studies in defining need
nonagenarians is safe and effective. J Vasc Surg 2010; 52: 1,140–1,146.
for rehabilitation or nursing home placement. Despite 2. Kurian AA, Suryadevara S, Vaughn D et al. Laparoscopic colectomy in
these subtle differences, the results from our review con- octogenarians and nonagenarians: a preferable option to open surgery? J Surg
firm that frail patients struggle to return to their own Educ 2010; 67: 161–166.
3. Hamel MB, Henderson WG, Khuri SF, Daley J. Surgical outcomes for patients
home after surgery. Surprisingly, there was only a differ-
aged 80 and older: morbidity and mortality from major noncardiac surgery. J Am
ence of a single day in overall LOS between frail and non- Geriatr Soc 2005; 53: 424–429.
frail patients. This may in part be due to the data coming 4. Patel SA, Zenilman ME. Outcomes in older people undergoing operative
from various healthcare systems (and the variation in intervention for colorectal cancer. J Am Geriatr Soc 2000; 49: 1,561–1,564.
availability of rehabilitation facilities) but it may also be 5. Ahmed N, Mandel R, Fain MJ. Frailty: an emerging geriatric syndrome. Am J
Med 2007; 120: 748–753.
explained by institutions keeping patients in hospital lon-
6. Bergman H, Ferrucci L, Guralnik J et al. Frailty: an emerging research and
ger while home circumstances are optimised. clinical paradigm – issues and controversies. J Gerontol A Biol Sci Med Sci
2007; 62: 731–737.
7. Cooper C, Dere W, Evans W et al. Frailty and sarcopenia: definitions and
Conclusions outcome parameters. Osteoporos Int 2012; 23: 1,839–1,848.
8. Cruz-Jentoft AJ, Baeyens JP, Bauer JM et al. Sarcopenia: European consensus
The results of this systematic review suggest that issues on definition and diagnosis. Age Ageing 2010; 39: 412–423.
associated with frailty should be addressed to improve 9. Cruz-Jentoft AJ, Baeyens JP, Bauer JM et al. Sarcopenia: European consensus
patient outcomes. An easily identifiable definition that is on definition and diagnosis. Age Ageing 2010; 39: 412–423.
10. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 19. Lee JS, He K, Harbaugh CM et al. Frailty, core muscle size, and mortality in
1986; 7: 177–188. patients undergoing open abdominal aortic aneurysm repair. J Vasc Surg 2011;
11. van Vledder MG, Levolger S, Ayez N et al. Body composition and outcome in 53: 912–917.
patients undergoing resection of colorectal liver metastases. Br J Surg 2012; 20. Robinson TN, Wu DS, Stiegmann GV, Moss M. Frailty predicts increased
99: 550–557. hospital and six-month healthcare cost following colorectal surgery in older
12. Lieffers JR, Bathe OF, Fassbender K et al. Sarcopenia is associated with adults. Am J Surg 2011; 202: 511–514.
postoperative infection and delayed recovery from colorectal cancer resection 21. Makary MA, Segev DL, Pronovost PJ et al. Frailty as a predictor of surgical
surgery. Br J Cancer 2012; 107: 931–936. outcomes in older patients. J Am Coll Surg 2010; 210: 901–908.
13. Peng P, Hyder O, Firoozmand A et al. Impact of sarcopenia on outcomes 22. Dasgupta M, Rolfson DB, Stolee P et al. Frailty is associated with postoperative
following resection of pancreatic adenocarcinoma. J Gastrointest Surg 2012; complications in older adults with medical problems. Arch Gerontol Geriatr
16: 1,478–1,486. 2009; 48: 78–83.
14. Cervera R, Bakaeen FG, Cornwell LD et al. Impact of functional status on 23. Xue QL. The frailty syndrome: definition and natural history. Clin Geriatr Med
survival after coronary artery bypass grafting in a veteran population. Ann Thorac 2011; 27: 1–15.
Surg 2012; 93: 1,950–1,954. 24. National Confidential Enquiry into Patient Outcome and Death. An Age Old
15. Afilalo J, Eisenberg MJ, Morin JF et al. Gait speed as an incremental predictor Problem. London: NCEPOD; 2010.
of mortality and major morbidity in elderly patients undergoing cardiac surgery. 25. Fried LP, Tangen CM, Walston J et al. Frailty in older adults: evidence for a
J Am Coll Cardiol 2010; 56: 1,668–1,676. phenotype. J Gerontol A Biol Sci Med Sci 2001; 56: M146–M156.
16. Lee DH, Buth KJ, Martin BJ et al. Frail patients are at increased risk for 26. Abellan van Kan G, Rolland Y, Houles M et al. The assessment of frailty in older
mortality and prolonged institutional care after cardiac surgery. Circulation adults. Clin Geriatr Med 2010; 26: 275–286.
2010; 121: 973–978. 27. Rodríguez-Mañas L, Féart C, Mann G et al. Searching for an operational
17. Peng PD, van Vledder MG, Tsai S et al. Sarcopenia negatively impacts short- definition of frailty: a Delphi method based consensus statement: the Frailty
term outcomes in patients undergoing hepatic resection for colorectal liver Operative Definition-Consensus Conference Project. J Gerontol A Biol Sci Med
metastasis. HPB 2011; 13: 439–446. Sci 2013; 68: 62–67.
18. Sündermann S, Dademasch A, Rastan A et al. One-year follow-up of patients 28. Kalyani RR, Varadhan R, Weiss CO et al. Frailty status and altered glucose-
undergoing elective cardiac surgery assessed with the Comprehensive insulin dynamics. J Gerontol A Biol Sci Med Sci 2012; 67: 1,300–1,306.
Assessment of Frailty test and its simplified form. Interact Cardiovasc Thorac 29. Ho YY, Matteini AM, Beamer B et al. Exploring biologically relevant pathways
Surg 2011; 13: 119–123. in frailty. J Gerontol A Biol Sci Med Sci 2011; 66: 975–979.