Abstract Introduction Colonoscopy is the gold standard test for investigating lower gastrointestinal symptoms and is an important therapeutic tool for colonic polypectomy. This paper is aimed at the general physician and examines the role of colonoscopy in very elderly patients by exploring the particular risks in this population, the yield of colonoscopy and potential alternative investigations. Sources of data Original research and review articles were identified through selective PubMed searches. Guidelines were identified through interrogation of national and international society websites in addition to PubMed searches. Areas of agreement Advanced age alone is not a reason to avoid investigation. The decision to perform colonoscopy in this population must take into account indication and yield, risks of the procedure and bowel preparation, physical fitness of the patient, potential alternative and the ability to consent. As a general rule, the principle of ‘first doing no harm’ should be applied and requires balancing of the risks of the procedure and preparation with the benefits of doing the test. Areas of controversy There is no defined upper age limit at which colonoscopy is contraindicated, however; the National Health Service Bowel Cancer Screening Programme stops inviting patients for screening and surveillance colonoscopy at age 75. Growing points and areas timely for developing research The concepts of ‘first do no harm’ and shared decision-making are not new but are increasingly important, particularly in this patient group. It is crucial to provide patients with information about risks, benefits and alternative investigations to empower their decision-making. colonoscopy, frailty, shared decision-making Introduction Colonoscopy is the gold standard test for investigating lower gastrointestinal (GI) symptoms and is also the modality of choice for colorectal cancer screening, colorectal polyp surveillance and inflammatory bowel disease (IBD) surveillance.1 Direct luminal intubation with a colonoscope allows biopsies to be taken. The procedure is also an important therapeutic tool for colonic polypectomy. This paper will examine the role of colonoscopy in very elderly patients for the non-endoscopist, in addition to exploring the particular risks in this population, the yield of colonoscopy, potential alternative investigations and a suggested pragmatic approach for the general physician. A focused PubMed literature search was undertaken to identify relevant literature, including the terms ‘colonoscopy’ and ‘very elderly.’ Reference lists of identified papers were also interrogated. Relevant national and International society guidelines were searched. The very elderly patient The life expectancy of the global population is rising, partly as a result of reduced child mortality rates and reduced mortality from infectious diseases in developing countries, additively as a result of improved mortality in the older population in developed countries.2–4 Despite an increase in overall life expectancy, these additional years are not necessarily disability-free and in the West may be associated with multiple long term conditions, polypharmacy, frailty and increased social care requirements.5,6 As such decisions behind medical intervention are often complex and must encompass individual patient characteristics and patient choice.7 Ageing is a functional decline over time usually represented by ‘chronological age’. The ageing process however is complex and involves cellular damage, genetic change and protein alterations which contribute to differing rates of ageing; the ‘biological age’.8–10 In addition to pathological processes, this accounts for the variability in functional status within chronological age groups.11,12 There is therefore no formal definition of ‘very elderly’ patients, however, patients of retirement age or over are generally considered elderly. Whilst comorbidity and disability increase with age, frailty is a separate entity described by Fried et al. as a ‘biologic syndrome of decreased reserve and resistance to stressors, resulting from cumulative declines across multiple physiologic systems, and causing vulnerability to adverse outcomes.’13 The presence of frailty is associated with increased falls, hospitalisation, disability and mortality.12,13 Various frailty indexes exist to identify older patients at risk of inappropriate prescriptions and to predict adverse outcomes.14,15 This paper focuses on colonoscopy in the very elderly, i.e. 80 years and over but the principles discussed may be applicable to younger patients who are frail and similarly they may not apply to the very fit octogenarian. Decision to perform colonoscopy ‘First, do no harm’ The decision to perform colonoscopy in the very elderly must take into account the indication and expected yield, risks of the procedure, risks of bowel preparation, physical fitness of the patient, potential alternative and the ability to consent. The principle of ‘first do no harm’ should be applied and requires balancing of the risks of the procedure and preparation with the benefits of doing the test. Advanced age alone is not a reason to avoid investigation—such rationale could be considered as age discrimination and could prevent patients from receiving diagnoses, receiving treatment and even prevent cure from disease. The decision to undertake colonoscopy should be made in partnership with the patient and in the UK must include informed consent with adherence to the Mental Capacity Act 2005 and the Adults with Incapacity (Scotland) Act 2000.16 Given that the prevalence of neurocognitive disorders such as dementia increases with age, consideration of the issue of capacity to consent is important.17 The clinician organising colonoscopy needs to ascertain the patient’s baseline cognitive function by liaising with those who know the patient well; family, friends and general practitioner. In patients with cognitive or sensory impairment, these discussions often take more time and require creative communication skills- booking extra time in clinic for such patients may be helpful to enable shared decision-making. Furthermore, the provision of simple written communication for the patient to reflect on following the consultation is an important aide-memoire. Upper age limits As mentioned previously, decisions about patient treatment and investigation should not be made upon age alone. The incidence of colorectal cancer increases with age, meaning investigation of lower GI symptoms may well pick up relevant, serious pathology. Within the symptomatic service, the decision to undertake colonoscopy in a patient over this age usually depends on the individual’s fitness. The British Society of Gastroenterology (BSG) guidelines suggest that the upper age limit for screening and surveillance colonoscopy for adenoma surveillance should usually stop at the age of 75 years, taking into consideration comorbidity and relative colorectal cancer risk.1 The adenoma-carcinoma pathway is the accepted sequence by which the majority of colorectal cancers arise through adenomas and is thought to take at least 10–15 years.18 Screening for adenomas beyond the age of 75 years is therefore unlikely to significantly improve life expectancy. The National Health Service (NHS) Bowel Cancer Screening Programme (BCSP) invites patients in England and Wales from 60 years of age and from 50 years of age in Scotland to complete biennial faecal occult blood tests (FOBt) with referral for colonoscopy where positive. Patients beyond the age of 74 are not invited and surveillance within the programme ends at age 74, and therefore formal national screening within the UK is not routinely offered in the very elderly. Individuals may however opt in after the age of 74. Risks of procedure It is crucial that the correct investigation is selected to answer the clinical issue in question and to avoid unnecessary risks associated with the procedure. Diagnostic colonoscopy is a relatively safe procedure, however, associated risks increase with therapeutic intervention. The main risks are of colonic perforation or bleeding. Cardiovascular and pulmonary complications may also occur as a result of sedation, gaseous distension or discomfort. Colonoscopic complication rates vary, with a recent UK audit suggesting a perforation incidence of 0.04% and a haemorrhage rate of 0.26%.19 The audit did not take into account late presentations of complications and therefore may under-represent the true figure. A systematic review and meta-analysis demonstrated higher complication rates in the elderly, largely driven by cardiovascular and pulmonary complications.20 Patients aged ≥80 years had a 70% higher risk of cumulative GI adverse events compared with patients under 80 years.20 Patients aged ≥80 years also had higher risks of perforation compared with those <80 years of age (Incidence Rate Ratio 1.6; 95% CI, 1.2–2.1; P = 0.9 for heterogeneity). Although GI bleeding rates and cardiovascular and pulmonary adverse rates were higher in those aged over 80 years, these were not statistically significant.20 Higher perforation rates may be explained by higher rates of diverticular disease in the older population, higher yield of polyps requiring therapeutic intervention and increased colon tortuosity in the elderly group.20,21 Although the increased risk of perforation is small and increased bleeding risk not significant in very elderly patients, it is important to consider the impact of that risk on the overall health of the individual patient and weigh-up potential benefits. Intra-procedural medications may also pose a risk to patients. Patients may choose to undertake the procedure using conscious sedation, which in the UK is usually composed of ‘midazolam’ and an intravenous opiate such as ‘Fentanyl’ or ‘Pethidine’. There is little specific evidence regarding sedation in very elderly patients and this is an area where further research is required. It has been observed that very elderly patients are more likely to require reversal of intravenous sedation and likely require lower doses to achieve the same effect as younger patients.22–24 An American evaluation of practice patterns demonstrated that endoscopists tend to give lower doses of sedation to elderly patients.25 ‘Hyoscine butylbromide (Buscopan)’, which may be used to improve views on withdrawal or to alleviate bowel spasm may also pose risk.26 A recent Medicines and Healthcare products Regulatory Agency update noted that serious adverse effects such as tachycardia, hypotension and anaphylaxis can result in fatal outcomes in patients with underlying cardiac disease.27 As comorbidity rises with age, ‘Hyoscine butylbromide’ should be avoided in cases of known or suspected underlying cardiac disease and in tachycardic patients. The BSG urges caution when using ‘Hyoscine butylbromide’ but advises weighing the benefits and risks. Risks of bowel preparation Aside from the risks of the procedure itself, the preparation used to clear the bowel can also be problematic in terms of purgative effect and risk. Patients must also undergo a period of restricted diet, fasting and later fluid restriction which can be problematic in those with diabetes or renal impairment. The aim of bowel preparation is to completely clear the bowel so that adequate views can be obtained to exclude pathology. Bowel preparation is extremely purgative. This may not be a problem in patients who are mobile and fit, however, patients with limited mobility may find it difficult. It is important to explain this to older patients. An elderly patient whose toilet is only accessible with a stair-lift may not manage the preparation at home. In these cases, in-patient admission for bowel preparation or alternative investigation to colonoscopy may need to be considered. Although there is a perception amongst clinicians that in-patient bowel preparation is more likely to be inadequate due to alien patient environment, a large multi-centre European study found that there was no difference between in-patient and out-patient preparation adequacy.28 Certain individual patient characteristics, such as chronic constipation, diabetes mellitus and incomplete bowel preparation intake, may affect the adequacy of bowel preparation.28 Although there is a paucity of research addressing bowel preparation within the very elderly population, a recent study found that diabetes, difficulty walking or performing activities of daily living were associated with poor bowel preparation in patients aged over 65.29 Poor bowel preparation is the main reason for failure to complete colonoscopy in patients aged 90 years and over.30 The BSG issued consensus guidance on the prescription and administration of oral bowel preparation in response to a National Patient Safety Agency alert which reported one death and 218 patient safety incidents within a 5-year period.31,32 Although the majority of these incidents resulted in no or low harm (93%), 6% caused moderate harm and 1 patient died.32 Medication errors included omitted medicine/ingredient (29%), wrong drug (23%) and wrong or unclear dose or strength/frequency (11%).32 Complications which may arise from bowel preparation include hypovolaemia, renal failure and electrolyte disturbances.31 Accurate prescription of bowel preparation and consideration of its potential interactions and side effects are particularly important in the very elderly population who are more likely to have multiple comorbidites and polypharmacy which could potentiate side effects. They may also have less physical reserve to deal with complications should they occur. Serum albumin concentration prior to bowel preparation may predict hypovolaemia in patients over 65 years old.33 The majority of bowel cleansing agents used in the UK fall into two groups; polyethylene glycol (PEG or macrogols) and sodium phosphate preparations. PEGs are non-absorbable iso-osmotic solutions which reduce the risk of significant fluid and electrolyte shifts; however, they often taste unpleasant and in order to achieve their purgative effect they must be diluted in large volumes of water.31 Sodium phosphate preparations tend to be diluted in smaller volumes of water and are hyper-osmotic, causing large volumes of water to shift into the colon. A meta-analysis showed that PEG and sodium preparations were equally effective but PEG preparations are more effective in ensuring right sided bowel clearance.34 PEG is felt to be relatively safe in terms of renal risk in patients over the age of 65.35 In general, because of their hyper-osmotic properties, sodium phosphate preparations should be restricted to patients who have no other comorbidities, and should be specifically avoided in patients with chronic kidney disease, congestive cardiac failure or hypertension.31 All oral bowel cleansing agents should be used with caution in patients with pre-existing chronic renal failure and liaison with the renal team is advised in patients undergoing dialysis or with advanced chronic kidney disease. Guidelines suggest that sodium phosphate preparations should be completely avoided in patients with renal failure.31 Furthermore, it is important to identify and consider withholding any medications which may potentiate renal failure in combination with bowel preparation, e.g. diuretics, angiotensin converting enzyme inhibitors and Angiotensin II receptor antagonists.31 Whilst specific data on bowel preparation is lacking in the very elderly population the dangers of bowel preparation are highly likely to be exacerbated in this population. Consideration should be given to research in this area. Polypharmacy Comorbidity increases with age, meaning that polypharmacy is common in older patients. Anti-platelet agents and anticoagulants are the most important concomitant medications when considering colonoscopy. Whilst ‘Aspirin’ can be safely continued for both diagnostic and therapeutic colonoscopy, P2Y12 anti-platelet agents such as ‘Clopidogrel’ and ‘Ticagrelor’ and anticoagulants including ‘Warfarin’ and the direct oral anticoagulants (DOACs) must be reviewed. The European Society of Gastrointestinal Endoscopy (ESGE) and BSG joint guidelines provide clear guidance on when these medications should be stopped and when they may be continued.36 Application of these guidelines is not always straight forward. In general, P2Y12 anti-platelet agents can be continued for diagnostic colonoscopy (i.e. colonoscopy without polypectomy), as can ‘Warfarin’ providing the International Normalised Ratio is within range. DOACs should be stopped at least 24 hours prior to the procedure, according to renal function. Patients on anti-platelet or anticoagulant medications undergoing therapeutic colonoscopy (i.e. colonoscopy with polypectomy) should be managed according to BSG and ESGE guidelines. Yield of procedure When investigating GI symptoms, it is important to choose a test which detects relevant pathology without exposing the patient to unnecessary procedural risks. The test therefore must answer the clinical question being asked. Significant findings of colonoscopy in the very elderly include colorectal cancer, diverticular disease and inflammation.37 Angiodysplasia may be relevant in those with significant lower GI bleeding or iron deficiency anaemia. Polyps may also be a significant finding in an elderly patient, however, this is controversial. While advanced polyps which are at risk of containing or developing colorectal cancer are significant findings, it could be argued that small or diminutive polyps which are deemed low risk are not significant as they do not cause symptoms and are unlikely to progress to significant pathology within a very elderly patient’s lifetime.18,38 The incidence of colorectal cancer, polyps ≥10 mm and diverticular disease are all higher in patients aged 65 years and older, however, new diagnoses of IBD decrease with age.21,39,40 The majority of studies examining yield in the very elderly population are limited by small study numbers. A Dutch study comparing yield in symptomatic patients aged younger than 80 years with those ≥80 years demonstrated that patients younger than 80 years are significantly more likely to have a normal colonoscopy (32.0% vs. 10.1%, P < 0.001).37 A British study of 316 patients ≥85 years demonstrated that 24.7% of procedures were normal, but explanatory pathology was found in 37% of completed cases.41 In terms of overall yield, 41.1% showed diverticular disease, polyps were found in 14.2%, colorectal cancer in 8.9%, IBD in 4.1% and angiodysplasia in 2.2%.41 Of those patients who were found to have colorectal cancer, the most common presenting symptoms were anaemia (53%), diarrhoea (17%) and haematochezia (17%). Interestingly, 68% of the patients found to have colorectal cancer underwent curative surgery.41 A study in Japan found that very elderly patients (age > 90 years) were significantly more likely to have advanced cancers than those in younger age groups.42 Another study demonstrated that cancer and advanced adenomas were more likely to be found in patients with anaemia (11% and 9%, respectively), haematochezia (7% and 14%, respectively), occult blood loss (7% and 14%, respectively) and altered bowel habits (2% and 7%, respectively).43 The UK National Bowel Cancer Audit 2017 found that patients over the age of 85 years were less likely to undergo treatment for colorectal cancer with curative intent (37% of cases).44 Identifying a cancer diagnosis is nonetheless important in enabling symptom control and prognosticating. As discussed, population screening for colorectal cancer in asymptomatic, low risk, very elderly individuals is not an indication for colonoscopy in the UK. This is supported by the extremely low yield of relevant pathology in such patients.43 Alternative investigations to colonoscopy Colonoscopy is the gold standard for investigation of lower GI symptoms. In very elderly patients, colonoscopy may not be appropriate due to patient choice, suboptimal patient fitness and inability to consent. Furthermore, colonoscopy may not be completed due to poor bowel preparation or discomfort.45 Elderly patient’s preference may differ from the referring doctor’s expectations of their preferred option and they should be given adequate information to come to an informed decision regarding investigation.46 Colonoscopy appears to be well-tolerated in elderly and elderly patients.47 The main alternative to colonoscopy is computed tomographic colonography (CTC), which requires the patient to drink oral contrast the day before the test (with or without bowel preparation). Oral bowel preparation may be avoided as ‘Gastrografin’ may cause diarrhoea due to its hyper-osmotic properties.31 A small plastic tube is then used to insert air or carbon dioxide to insufflate the bowel and the patient is asked to change position during the scan to enable views. A large UK trial demonstrated no significant difference in detection rates of colorectal cancer and large polyps between CTC and colonoscopy; however, undertaking CTC precludes the ability to take biopsies or undertake polypectomy and may miss smaller lesions.48–50 The significance of smaller lesions could be argued in the very elderly population. Extra-colonic findings were present in 59.6% of CTCs and were more common in older patients. 8.5% of these findings required further investigation.50 In terms of safety, CTC is extremely safe, with a recent review of 50 860 patients across three studies demonstrating a total perforation rate of 0.035% (symptomatic 0.015%, asymptomatic 0.013%).51,52 Intravenous sedation is not used in CTC and therefore the risk of cardiovascular complications is extremely low. A large multi-centre retrospective analysis of 17 067 CTCs revealed three vasovagal episodes and one episode of cardiac angina.51,53 Furthermore, CTC is significantly more acceptable to patients than colonoscopy or barium enema, the latter of which the authors believe is an out of date test due to high colorectal cancer miss rates and poor acceptability to patients.48,50,54,55 There are issues with CTC in very elderly patients. Whilst it is generally safer and better tolerated than colonoscopy the tolerability is worse than patients expect.56 CTC is more invasive than simple contrast CT. It involves having a rectal catheter inserted to inflate the colon and often use of a purgative. Patients must be aware of this as many are poorly prepared for the procedure. If the CTC yields significant pathology then further investigation with further bowel preparation and colonoscopy is usually required in order to remove lesions or gain histology. It is therefore important that clinicians are clear what action will be taken depending upon CTC results. If a patient is not fit for colonoscopy and polypectomy, then the decision should be taken pre-CTC that polyps will not be pursued if found. In extremely frail patients, CTC may be too invasive. The indication in these patients is likely to be to diagnose or exclude very serious pathology such as cancer and a CT with contrast without purgative and rectal insufflation may be appropriate in this setting. Conclusions In an age of ‘too much medicine’, it is important that over investigation and over treatment are avoided. The first rule of medicine is first do no harm and this rule should be strongly considered when considering undertaking interventional procedures on very elderly patients. Colonoscopy is a relatively safe procedure but done for poor indications or without a clear rationale, it becomes a procedure with risk but unclear benefit. It is important for clinicians to be clear what the purpose of an investigation is and to consider potential sequelae if abnormalities are found. Whilst yield of pathology in elderly patients is high, the relevance of the pathology may be low. A very elderly patient is likely to die with a small colorectal polyp (from another cause) and not of a small colorectal polyp (it is very unlikely to turn into cancer). Endoscopic complications such as perforation after polypectomy in a very elderly patient may be extremely serious due to increased comorbidity and reduced functional reserve, therefore a procedure should only be undertaken if it will clearly benefit and not harm an individual. Screening Colonoscopy has no proven benefit in very elderly patients and should not be undertaken. Patients referred with symptoms should be assessed to determine the purpose of investigation. This is likely to be to diagnose or exclude cancer or provide explanation and management of symptoms. If a patient is relatively free from comorbidity and fit enough to take bowel preparation then colonoscopy should be undertaken as first choice. This allows a thorough diagnostic test and the ability to take tissue for histology. If the patient has multiple comorbidities, is frail and at risk from bowel preparation then CTC should be considered but with a clear plan for how any abnormalities (e.g. polyps) should be dealt with if they are found. It is often appropriate to decide that only life-threatening pathology will be investigated and managed further. Colonoscopy is a very important investigative and therapeutic tool. It is generally safe and well-tolerated but is highly invasive and has the potential to cause significant harm and to find abnormalities that may have little clinical relevance to a particular patient. It has a clear role in very elderly patients but should be used with caution weighing up risks and benefits to the given individual. As in all areas of medicine, patients must be integral to decision-making regarding their own health. Together, clinicians and patients should weigh-up the options and do the right thing for that individual patient. 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British Medical Bulletin – Oxford University Press
Published: Jun 2, 2018
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