5 Things Every Family Physician Should Know in 2015
March 9, 2015
5 THINGS EVERY PHYSICIAN SHOULD KNOW IN 2015
Best Strategies for Treatment of Hypertension
Although much remains unknown about the best therapies for treatment of hypertension, an increasing body of evidence sheds light on some of the important questions.
Should we be treating patients with mild hypertension? A Cochrane review analyzed four randomized controlled trials involving almost 9000 patients with mild hypertension (systolic blood pressure [SBP] 140-159 mm Hg and/or diastolic blood pressure [DBP] 90-99 mm Hg) and without cardiovascular disease (CVD) treated with antihypertensive therapy or placebo for an average of 4-5 years. The reviewers found no difference between treated and untreated individuals in the incidence of coronary heart disease, stroke, total cardiovascular (CV) events, and death. Furthermore, about 9% of patients treated with drugs discontinued treatment owing to adverse effects. The bottom line? Treating mild hypertension provides little prevention of CVD in the short term; use the least bothersome first-line agent as possible.
Is sodium restriction helpful? A meta-analysis of 34 trials examining the effect of salt restriction on blood pressure (BP) found a mean reduction in SBP of 5.39 mm Hg and mean DBP reduction of 2.82 mm Hg. From a population viewpoint, these were deemed to be important reductions in BP and were found in both hypertensive and normotensive individuals, irrespective of sex and ethnic group. The investigators further speculated that the significant association between the reduction in 24-hour urinary sodium and the fall in SBP indicates that larger reductions in salt intake would lead to larger SBP reductions. There were small physiologic increases in renin activity, aldosterone, and noradrenaline. Renin increases the amount of angiotensinogen in the blood, which could increase BP; the release of aldosterone has the potential to increase both sodium retention and potassium secretion, which also could increase BP.
How low should sodium intake go? The 2010 Dietary Guidelines for Americans recommend reducing daily sodium intake to less than 2300 mg for the general population and to 1500 mg among higher-risk groups including African Americans, adults aged 51 years and older, and those with hypertension, diabetes, or chronic kidney disease (CKD). However, a 2013 report from the Institute of Medicine concluded that current evidence did not support this lower recommendation for some populations. So, at least for now, one size appears to fit all. The bottom line? Limiting the use of a salt shaker is unlikely to improve any short- or long-term outcomes. Instead, encourage patients to limit their intake of prepared foods (canned soups, store or restaurant prepared foods) that contain large amounts of hidden sodium.
Could potassium be the answer? A systematic review and meta-analysis of 22 randomized controlled trials and 11 cohort studies examined the effects of potassium intake on BP, renal function, lipids, catecholamine concentrations, all-cause mortality, CVD, stroke, and coronary heart disease. Increased potassium intake reduced BP with no adverse effect on lipids, catecholamine concentrations, or renal function in adults. The highest intake of more than 4700 mg/day was associated with the largest SBP reduction. However, the average American consumes only 2640 mg/day. The highest potassium concentrations are found in figs, molasses, seaweed, dates, prunes, tree nuts, avocados, bran cereal, wheat germ, and lima beans. Just one fourth of a teaspoon of Morton® salt substitute provides more potassium than such frequently cited food sources as bananas, oranges, potatoes, and spinach. The Office of Disease Prevention and Health Promotion in the Department of Health and Human Services provides an online table of foods ranked by mg of potassium per standard serving.
If you are going to treat, should you use chlorthalidone or hydrochlorothiazide? To try to better answer this question, an observational cohort study of almost 30,000 individuals aged 65 years or older who had not had a hospitalization for major CV event in the previous year and were newly treated with chlorthalidone or hydrochlorothiazide was conducted in Canada. The investigators concluded that the risk for death or adverse CV events was similar and use of chlorthalidone in older adults was not associated with fewer adverse CV events or deaths compared with hydrochlorothiazide. The chlorthalidone group was, however, more likely to be hospitalized with hypokalemia (hazard ratio [HR], 3.06) or hyponatremia (HR, 1.68). And thanks to the Joint National Committee 8 (JNC 8), thiazides are not the only choice for first-line treatment.
What does JNC 8 say? In December 2013, the long-awaited adult hypertension management guidelines from JNC 8 were released to much fanfare and controversy. Some of the new recommendations include:
- In patients aged 60 years or older, start treatment for SBP >150 mm Hg or DBP >90 mm Hg and treat to under those thresholds.
- In patients aged 18-60 years, treatment initiation and goals should be 140/90 mm Hg.
- The same goals apply to patients with diabetes or CKD.
- In nonblack patients, initial treatment can be a thiazide-type diuretic, calcium channel blocker (CCB), angiotensin-converting-enzyme (ACE) inhibitor, or angiotensin receptor blocker (ARB).
- For black patients, initial therapy should be a thiazide-type diuretic or CCB.
- In patients aged 18 years or older with CKD, initial or add-on therapy should be an ACE inhibitor or ARB, regardless of race or diabetes status.
Making Lifestyle Change Work for Patients With Diabetes
The Action for Health Diabetes (Look AHEAD) study is a national, multicenter, randomized, controlled trial that is examining the long-term effects of an intensive lifestyle intervention program designed to achieve and maintain weight loss by reduced caloric intake and increased physical activity in more than 5000 overweight or obese patients with type 2 diabetes. Patients received weekly treatment with group and individual sessions for the first 6 months, with bimonthly sessions thereafter. The trial was stopped early at 9.6 years after finding that the intervention group had higher weight loss (8.6% vs 0.7% at 1 year; 6.0% vs 3.5% at study end) as well as larger reductions in glycated hemoglobin levels, greater initial improvements in fitness, and improved CV risk factors, except for low-density-lipoprotein cholesterol levels. However, the primary outcome of CV events was not affected. Does this mean that lifestyle intervention is not the answer? No. But it does mean that it may not be the only answer. Equally it is not an easy answer. The intensive intervention provided in this trial is not feasibly reproduced in a busy primary care setting. However, primary care is the best setting to provide smart, evidence-based weight loss suggestions and reinforce them at each visit. Recommendations should include:
- Increase intake of vegetables and fruit but not fruit juice. A cohort study conducted in Spain found a significant reduction in diabetes with every three servings per week, with the highest degree of fruit and vegetable intake associated with the lowest risk for weight gain (odds ratio [OR], 0.22).
- Increase vegetable but not animal protein. A study of 1730 employed white men aged 40-55 years found a statistically significant, positive association between animal protein intake and obesity; those in higher quartiles of vegetable protein intake had lower odds of being obese. The researchers calculated a relative risk (RR) for obesity of 4.62 in those at the highest quartile of animal protein intake; the comparable RR for those at the highest quartile of vegetable protein intake was 0.58.
- Mediterranean diet beats low-fat diet. A randomized controlled trial of 7000 patients at high CV risk but without CVD assigned participants to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Patients were followed for a mean of 4.8 years. The Mediterranean diet, supplemented with either olive oil (approximately 4 tablespoons/day) or nuts (average of 3 servings/day), reduced the risk for major CV events. The unadjusted hazard ratios for both diets was 0.70 (95% CI, 0.53-0.91 for olive oil or 0.94 for nuts). Moreover, participants in the two Mediterranean-diet groups significantly increased weekly servings of fish (by 0.3 servings) and legumes (by 0.4 servings) in comparison with those in the control group.
Happy Spitters Do Not Have a Disease
New guidelines from the American Academy of Pediatrics released in 2013 emphasized what we all know—that gastroesophageal reflux (GER) is normal and does not require treatment beyond perhaps such lifestyle changes as feeding and positioning. GER with complications GER disease (GERD)—should likewise be treated with lifestyle changes. Medications should be reserved for children who do not respond to more conservative therapy. The guideline authors concluded: "Best practice involves both identifying children at risk for complications of GERD and reassuring parents of patients with physiologic GER who are not at risk for complications to avoid unnecessary diagnostic procedures or pharmacologic therapy."
SSRIs and Pregnancy
A cohort study published in JAMA involving more than 30,000 women in Scandinavia with 1.6 million births (6054 stillbirths, 3609 neonatal deaths, and 1578 postneonatal deaths) concluded that selective serotonin reuptake inhibitor (SSRI) use was not associated with any of the following negative outcomes:
- Stillbirth: OR, 1.17 (confidence interval [CI], 0.96-1.41; P = .12)
- Postneonatal death: OR, 1.34 (95% CI, 0.97-1.86; P = .08)
- Neonatal death: OR, 1.23 (95% CI, 0.96-1.57; P = .11)
Yes, women exposed to an SSRI presented with higher rates of stillbirth (4.62 vs 3.69 per 1000, P = .01) and postneonatal death (1.38 vs 0.96 per 1000, P = .03) than those who were not. However, these associations disappeared in multivariable models. Before you reach for your prescription pad, however, the results of another large, case control study conducted in Sweden with approximately 1700 children with autism should be considered. After adjustment for potential confounders, in utero exposure to both SSRIs and nonselective monoamine reuptake inhibitors (tricyclic antidepressants) was associated with an increased risk for autism spectrum disorders (ASDs), particularly without intellectual disability. The study authors emphasized that it cannot be determined whether this association is causal or reflects the elevated risk for ASD in women with severe depression. Even if the association is causal, the use of these agents explained less than 1% of the cases of ASD in this cohort, and their use is unlikely to be a significant contributor to the rise in ASD. The researchers concluded that decisions about use of SSRIs during pregnancy must take into account other perinatal outcomes and the risks associated with maternal mental illness.
The Rise in Autism
An analysis of data from the Nurses' Health Study II looked at 325 children with ASD matched with 22,000 control children. After adjustment for socioeconomic status and other potential confounders, the investigators concluded that the highest exposures to diesel, lead, manganese, mercury, methylene chloride, and overall metals were associated with increased risk for ASDs (OR, 1.5-2.0). The linear trend found in this study adds to existing evidence that maternal exposure to air pollution in the perinatal period may increase risk for ASD in children.
Frank J. Domino, MD
Management of renal colic
March 11, 2015
MANAGEMENT OF RENAL COLIC
- Renal colic is a common presentation (lifetime risk 12% in men, 6% in women) causing pain and morbidity
- Non-contrast computed tomography is the imaging method of choice, owing to its high sensitivity and specificity
- Non-steroidal anti-inflammatory drugs offer the best initial analgesia, with opiates as a second line treatment
- Up to 80% of stones will pass spontaneously, and increasing evidence supports medical expulsive therapy
- Patients with coexistent obstruction and sepsis should have urgent relief of the obstruction with either percutaneous nephrostomy or retrograde stent
- Ureteroscopy and extracorporeal shockwave lithotripsy are highly successful treatments for ureteric stones
Urinary stone disease is increasingly prevalent, with a lifetime risk of about 12% in men and 6% in women. Age of onset of a first stone episode for men rises from their 20s and peaks at age 40-60 years, with an incidence of three cases per 1000 population per year. Women appear to peak a little younger in their late 20s. The male to female ratio is narrowing, with one study showing a reduction from 1.7:1 to 1.3:1 over a five year period. Presentation varies according to geographical and seasonal factors, with higher incidences in warmer climates and during the summer months.
This review includes the latest information from meta-analyses, systematic reviews, randomised trials, current guidelines, and other peer reviewed evidence to provide a background on presentation, investigation, and medical and surgical management of patients with renal colic.
Sources and selection criteria
We performed a PubMed search to identify peer reviewed original articles, meta-analyses, and reviews using the search terms “renal colic” and “ureteric stone”. We also reviewed national and international guidelines, and the Cochrane Collaboration and clinical evidence databases. We considered only papers written in English, with the emphasis on more recent articles if available or if we deemed the scientific validity to be sufficient.
What are urinary stones?
Urinary stones are formed by the aggregation of crystals with a non-crystalline protein (matrix) component. These crystals clump together to form a stone and then move when they reach a certain size and pass down the ureter, frequently causing colic symptoms. Eighty per cent of stones contain calcium, most commonly in the form of calcium oxalate (60%). Calcium phosphate accounts for 20% of stones, with uric acid forming approximately 7%,3 although this uric acid proportion may rise in obese patients. Another 7% are infection stones containing magnesium ammonium phosphate. Bladder stones usually have a different cause, often as a result of bladder outflow obstruction.
Who gets urinary stones?
The incidence of stones is higher in warmer climates, owing to a combination of dehydration and sun exposure (vitamin D). Obesity is also a risk factor, with large epidemiological studies showing both high body mass index and weight as independent risk factors for stones. There is a 2.5 times greater risk if a patient has a family history of stone disease. This increase is probably a genetic predisposition but may also be due to similar environmental factors such as dehydration and diet. Any anatomical abnormality of the urinary tract (such as a horseshoe kidney) indicates a higher risk of stone formation, as well as several medical disorders such as primary hyperparathyroidism, renal tubular acidosis, myeloproliferative disorders, all chronic diarrhoeal conditions (for example, Crohn’s disease), and gout. Occupations involving work in a hot environment (for example, kitchen workers) are also at risk due to dehydration. Previous stone formation is a risk factor, with a 30-40% chance of forming a second stone within five years of the initial episode. Both observational studies and a randomised trial (compared with control) have shown the importance of fluid intake—patients producing less than 1 L of urine per day are at highest risk of stone formation, while producing 2 L of urine per day substantially reduces the risk of stone episodes.
What is renal colic?
Renal colic describes the pain arising from obstruction of the ureter, although ureteric colic would be a more accurate term. The pain is caused by spasm of the ureter around the stone, causing obstruction and distension of the ureter, pelvicalyceal system, and renal capsule. Although the most common cause is a stone, the term “renal colic” actually refers to a collection of symptoms attributed to the kidney and ureter. There are other intrinsic or occasionally extrinsic causes such as lymphadenopathy, although extrinsic causes tend to present with milder and more chronic discomfort. Other common intrinsic causes are blood clots (from upper tract bleeding) or sloughed renal papilla (which can occur in sickle cell disease, diabetes, or long term use of analgesics).
What are the symptoms of renal colic?
The classic presentation of renal colic is the sudden onset of severe loin pain (in the costovertebral angle, lateral to the sacrospinus muscle, and beneath the 12th rib), often described as akin to labour pains. Depending on the site of obstruction, the pain will radiate to the flank, groin, and testes or labia majora. This pain can be a useful method of judging the level of obstruction. If a stone is at the vesico-ureteric junction (VUJ), the patient may often complain of strangury (the urgent desire to pass urine with poor volumes, urinary frequency, and straining) due to irritation of the detrusor muscle from the stone. Nausea with vomiting is common. The pain is a colic, and thus comes in waves of varying intensity. Patients will often have completely pain free spells between attacks. Furthermore, they are often restless and cannot get comfortable, by contrast with peritonitic conditions in which patients remain still. Visible haematuria may occur, but in these cases it is important to ensure that the pain is not secondary to a clot as a result of other upper tract pathology. If concomitant urinary infection is present, the patient could complain of fevers and sweats. The table⇓ lists possible differential diagnoses.
How should a person presenting with acute flank pain be assessed?
The underlying cause of acute flank pain is not always a urinary stone, and other important conditions can mimic this. A thorough history and examination are important to determine further management, with particular emphasis on eliciting the typical site and nature of the pain of renal colic, and exclusion of symptoms and signs suggesting that acute hospital admission is needed (boxes 1 and 2). In men, the testes must be examined because scrotal pathology may rarely present solely with abdominal pain. All patients must have their temperatures documented, and pyrexia should prompt immediate referral. A leaking abdominal aortic aneurysm can mimic left sided renal colic, and patients at high risk, such as those older than 60 years and with known arteriopathy (particularly if not previously a stone former), need immediate referral for imaging.
Box 1: Indications for acute hospital admission
- Diagnostic uncertainty (consider admission for patients older than 60 years, because a leaking aortic aneurysm could present with similar symptoms)
- Inability to obtain or maintain adequate pain control
- Presence of significant fever (>37.5°C) in association with suspected renal colic
- Renal colic in patient with solitary or transplanted kidney
- Suspected bilateral obstructing stones
- Impending acute renal failure
- Inability to arrange early investigation or urological assessment
Box 2: Signs of sepsis
- Fever (>37.5°C)
- Facial flushing
- Tachycardia (especially once pain relieved)
- Loin tenderness
When can a patient be managed in a primary care or outpatient setting?
Patients with first presentation of renal colic are often seen in the emergency department, owing to both the severity of the pain and anxiety as to the cause. However, for patients in whom the diagnosis is clear, adequate pain relief can be achieved, and there are no complicating factors (box 1), it may be possible for a general practitioner to diagnose and manage patients with renal colic in the community and avoid acute hospital admission. This management is especially true for recurrent stone formers.
If the decision is taken to manage the patient in a community setting, urgent imaging must be arranged to confirm the diagnosis and assess the likelihood of spontaneous stone passage. This confirmation could require liaison with radiology to ensure an appropriate timescale is achievable. Little evidence indicates what this timescale should be. Expert consensus has suggested that seven days is the maximum acceptable interval, and inability to achieve this could necessitate hospital admission. Urology outpatient assessment should occur within seven to 14 days.
A common scenario is of a patient who is diagnosed in the emergency department with computed tomography (CT) and discharged home with conservative management. The patient should be advised that further episodes of pain are possible and that they may be caused by the stone passing. The patient should be supplied with non-steroidal anti-inflammatory drugs (NSAIDs) for pain relief. Usually, these patients do not require readmission unless the pain is severe. A need for further scanning by CT would be rare, and second presentation to the emergency department would require referral to a urologist.
When does a patient with renal colic require hospital admission?
Inability to control pain and provide adequate analgesia are criteria for acute hospital referral. Some clinical scenarios are of higher risk to the patient (box 1), and should suggest a lower threshold for referral into secondary care. In particular, any signs of urinary sepsis must be excluded (box 2); an obstructed infected kidney is an emergency because patients can rapidly deteriorate with overwhelming sepsis.
What investigations are needed when a stone is suspected?
Expert guidelines from the British Association of Urological Surgeons (BAUS) and College of Emergency Medicine state that all patients should have a urine dipstick documented. However, the sensitivity of haematuria in patients with ureteric stones is about 90%, and 40% of patients presenting with acute flank pain and haematuria do not have urolithiasis.9 Expert opinion suggests that the diagnosis and decision on whether to perform imaging should not be based solely on the presence or absence of haematuria. The presence of leucocytes and nitrites would support a diagnosis of urine infection, and the expert guidelines state that a midstream urine sample should be sent for culture.
Expert guidelines state that determining full blood counts (for white cell counts) and renal function should be considered, which is mandatory in patients with pyrexia or a single functioning kidney. Patients with proven stone formation should have basic metabolic studies measuring serum calcium and urate.
Most patients assessed in the emergency department will proceed to immediate imaging for a definitive diagnosis and management plan. However, if the pain has already resolved, there is no sepsis, and the patient has a normal contralateral kidney, immediate imaging is not mandatory and urgent imaging and review can be organised. The exact timing of this approach will depend on local availability, but it is advantageous to make a firm diagnosis and management plan. In the only trial that analysed this, researchers arranged imaging within two to three weeks, although other expert consensus opinion suggests a timeframe of seven days.
Non-contrast CT (NCCT) (fig 1⇓) has become the imaging method of choice for investigating acute flank pain. Several studies have shown consistently better results from NCCT than from intravenous urograms (IVUs; fig 2⇓) (NCCT sensitivity 94-100% and specificity 92-100% v IVU 51-87% and 92-100%, respectively). Radiation doses for NCCT can be reduced to similar levels as IVU by using a low dose protocol while maintaining diagnostic accuracy. NCCT has other benefits over IVUs, including speed of the test, detection of other pathology, and eliminating risks of nephrotoxicity or of allergic or anaphylactic reactions from the intravenous contrast.10 Guidelines from the BAUS, European Association of Urology (EAU), and American Urological Association recommend NCCT as the definitive investigation. If the stone is visible on the scout film, a plain radiograph of the kidneys, ureter, and bladder is not required, although such a radiograph would be needed if the stone was not visible, to assess visibility for directing the modality of follow-up imaging.
Fig 1. Representative axial slices of the kidneys, ureter, and bladder for renal colic, using NCCT. (A) Normal contralateral (left) kidney, with hydronephrosis of the right kidney and peri-nephric fat stranding indicating obstruction. (B) Distal ureteric stone (4 mm in diameter) with peri-ureteric oedema (rim sign) differentiating it from a phlebolith; the dilated ureter could also be traced down to the stone
Fig 2. IVU, 1 h after contrast injection, showing a normal left kidney and dilated right pelvicalyceal system. The ureter is dilated all the way to the lower ureter (where a small calculus was visible on plain imaging). The image should be taken after micturition to allow the ureter to be traced to the bladder
Ultrasonography is a cheap alternative as a primary diagnostic screening tool, particularly in thinner patients. It is good at identifying stones (particularly those >5 mm in diameter) within the pelvicalyceal system. Patients should be scanned with a full bladder to identify stones at the VUJ. However, stones elsewhere in the ureter (between the pelvi-ureteric junction (PUJ) and VUJ) are unlikely to be seen. Secondary signs, such as dilatation which may suggest an obstructing stone, improve the test’s sensitivity. It is the first line test in pregnancy and children.
Plain radiography of the kidneys, ureter, and bladder
Plain radiography of the kidneys, ureter, and bladder could be useful, with a sensitivity of 44-77% and specificity of 80-87%.10 Detection rates of radiography and ultrasonography combined could approach those of CT if in the most experienced hands, but a NCCT will be required if uncertainty remains. The combined approach is certainly reasonable if CT is not immediately available or if radiation dosing needs to be minimised.
Where are stones usually located?
Anatomically, the three narrowest parts of the ureter are at the PUJ, in the mid-ureter where the ureter crosses the iliac vessels, and at the VUJ. The most common site at presentation by far is at the VUJ; 60.6% of stones were found in this location by a retrospective review of 94 patients admitted to the emergency department with colic. The study also found 23.4% of stones in the proximal ureter; 10.6% at the PUJ; and only 1.1% at the level of the iliac vessels.
What initial analgesia and advice should be given?
NSAIDs and opiates are the mainstay of treatment. Systematic reviews have shown that NSAIDs achieve a greater reduction in pain scores and that patients are less likely to require additional analgesia than those treated with opiates. Furthermore, opiates (particularly pethidine) are associated with higher rates of adverse effects such as vomiting. Thus, NSAIDs should be used as first line analgesia unless a patient has a contraindication to their use (for example, history of peptic ulceration, known or suspected renal impairment, severe asthma). A Cochrane review of analgesia in renal colic was unable to determine which NSAID is best. The BAUS guidelines suggest oral or parenteral diclofenac as first line treatment, although choice will depend on local policies. If an opioid is used, it is recommended that pethidine is not used, owing to a high association with vomiting. Often patients are advised to increase oral fluid intake to accelerate stone passage, and some centres have used high volume intravenous fluid replacement or diuretics to achieve the same outcome. A Cochrane review found no convincing evidence to support these high volume strategies. There is no guidance on what patients should be advised, but our personal opinion would be to advise 2 L of oral fluid per day to ensure hydration, especially if receiving nephrotoxic agents. In one randomised trial, local warming using an electric blanket applied to the lateral abdomen and lower back was found to be an effective method of improving pain control (compared with controls (no warming)), particularly in a community setting.22 Acupuncture is used extensively in some parts of the world, and one randomised study showed equivalent effect compared with an intramuscular analgesic. There is low quality evidence for the use of anti-spasmodic drugs in renal colic, with no benefit observed in one randomised trial of hyoscine versus placebo. However, another randomised study suggested some benefit to intravenous papaverine in patients with ongoing pain after diclofenac. If a stone is passed and can be obtained from the urine, biochemical analysis can be performed (recommended in first time stone formers), which will avoid the need for any further imaging as long as symptoms have settled. Therefore, asking the patient to sieve their urine may be beneficial.
What is the chance of stones passing spontaneously and how long does it take?
Whether a stone will pass spontaneously depends on its size and location. In one single centre study analysing 172 patients by stone location, the passage rates were 48%, 60%, 75%, and 79% for proximal, mid, distal ureteric, and VUJ stones, respectively. When analysed by stone size, the rates were 76%, 60%, 48%, and 25% for 2-4 mm, 5-7 mm, 7-9 mm, and >9 mm diameters, respectively. A meta-analysis of available studies (328 patients) showed an overall passage rate of 68% for stones at least 5 mm in diameter and 47% for stones of 5-10 mm. A more recent report of 656 patients chosen to be managed conservatively, showed an overall passage rate of 86% (without medical expulsive therapy). Of stones that passed, 55.3%, 73.7%, and 88.5% did so within seven, 14, and 28 days, respectively. The mean time to passage was 6.8, 12.6, 14.8, and 21.8 days for stone sizes of at least 2 mm, 2-4 mm, 4-6 mm, and 6-8 mm, respectively, although 42.5% of stones larger than 6 mm did not pass within two months. Intervention was significantly more likely for proximal stones larger than 6 mm in size. In a smaller but much quoted study (75 patients), the mean time to stone passage was similar although the intervention rates were higher (50% for stone diameter >4 mm). Of stones up to 6 mm in diameter that did pass, 95% did so within four to six weeks.
What is the role of medical expulsive therapy?
Growing evidence indicates that treatments can increase the passage rates of stones by relaxing ureteric smooth muscle, either by α1 receptor blockade or calcium channel pump inhibition. Several studies have used nifedipine, while a range of α blockers have shown equivalent efficacy suggesting a class effect. In a meta-analysis, patients given medical expulsive therapy had a 65% (relative) greater likelihood of stone passage than controls (no treatment), and the number needed to treat was four. In another analysis, the absolute benefit with α blockers was 29% over controls, and only 9% with nifedipine. Not only do α blockers increase expulsion rates, but they also reduce time to expulsion, pain episodes, perceived pain scale, and analgesic requirements. Most of these studies are for stones in the distal ureter and smaller than 10 mm in diameter. Since small stones (less 5 mm) will probably pass anyway, the greatest treatment effect has been for sizes of 5-10 mm. Only one randomised study has specifically investigated upper ureteric stones. Stones smaller than 5 mm had a higher passage rate with tamsulosin than no treatment (71.4% v 50%), while 5-10 mm stones showed a benefit in terms of relocating to the distal ureter. From these studies, it is not surprising that the guidelines advocate medical expulsive therapy. Patients should be warned of the adverse effects of the drugs, and that it is an off-label indication. Women should be advised to use contraception to avoid pregnancy while taking the drug.
How long is it safe to leave a stone?
Existing evidence is weak. In old animal experiments with complete unilateral obstruction, irreversible loss did not occur before two weeks, although total renal loss can occur by six weeks. Fortunately, stones usually only cause partial obstruction. The guidelines recommend periodic evaluation if a stone is treated conservatively, with ultrasonography to check for hydronephrosis. If a stone has not passed within four to six weeks, it is unlikely to do so and intervention will probably be required.
When is urgent surgical intervention required?
Emergency surgical intervention is recommended in four situations: presence of an obstructed infected kidney, obstruction of a solitary kidney, bilateral obstruction, or uncontrolled pain. Infection in the presence of obstruction requires emergency surgery. Patients can deteriorate quickly with profound hypotension and septic shock, usually due to Gram negative organisms. Aggressive fluid resuscitation with broad spectrum intravenous antibiotics should be instituted and support from an intensive care unit may be required. Antibiotic delivery into the obstructed system is limited, and thus urgent decompression is indicated, which can be achieved either with a percutaneous nephrostomy or a retrograde ureteric stent. A nephrostomy tube is typically inserted by interventional radiologists under local anaesthesia or sedation with direct needle puncture into the collecting system through the loin. A retrograde stent is inserted with a cystoscope via the bladder by urologists in the operating theatre using a cystoscopy. A randomised trial in this setting showed no significant difference in outcomes between the two interventions, and consequently both the BAUS and EAU guidelines advocate the use of either. The choice will depend on local preference and availability; stone characteristics; and patient factors such as obesity, coagulopathy, and suitability for anaesthesia. Either way, only decompression of the collecting system should be obtained, and the stone must not be treated until the patient has fully recovered and the sepsis resolved.
What follow-up imaging should be used?
If stones are managed conservatively, the evidence for timing and modality of follow-up imaging is limited. If a patient passes the stone, no further imaging is required. If the stone was visible on the NCCT scout film, a radiograph of the kidneys, ureter, and bladder can be used to assess the stone’s progress. If the stone was not visible at the time of NCCT, a radiograph should have been performed at that time, because 10% of stones will still be visible. For follow-up, the expert panel recommends a plain radiograph of the kidneys, ureter, and bladder to check for the stone as well as ultrasonography to assess the degree of hydronephrosis. If the patient is symptomatic and those investigations are normal, low dose NCCT is recommended. Stones that are radiolucent will also need low dose NCCT.
What treatment options are available for the stone?
When to actively treat a stone will depend on size, location, ongoing symptoms, local availability, and patient preference. Most units will conservatively manage patients with stones smaller than 10 mm, controlled pain, normal renal function, and no signs of sepsis. If stones have not passed within four to six weeks, they are unlikely to do so, and very few pass after eight weeks. Patient preference is paramount, especially in situations where commitments necessitate a predictable clinical course or they intend on foreign travel. A patient’s intention to travel would be an indication for prompt stone treatment, and patients with ureteric stones should be advised of the risks of developing colic during a flight. If the flight had to be diverted, patients could be liable for medical costs since their insurance policy would probably be invalidated. Indications for initial active treatment of stones are low chance of spontaneous passage, persistent pain, ongoing obstruction, and renal insufficiency. If coexistent infection is present at admission for treatment, renal drainage only should be conducted. The main treatment options are extracorporeal shockwave lithotripsy (ESWL) or ureteroscopy. ESWL is usually an outpatient procedure performed with analgesia or sedation. A shockwave is generated and focused on the stone. The procedure is generally well tolerated but is not available in all urology units, and could require more than one treatment. Ureteroscopy is typically done under general (or spinal) anaesthesia. Usually a rigid or semi-rigid ureteroscope is used, although evidence suggests that flexible ureteroscopy has better clearance rates for upper ureteric stones. The vast majority of stones will be cleared in one treatment, but an indwelling stent may be required for some time afterwards. Both procedures have high success rates for all ureteric stones. A meta-analysis of available studies has shown ESWL to have stone free rates of 82%, 73%, and 74% for proximal, mid, and distal ureteric stones, respectively. Corresponding success rates for ureteroscopy were 82%, 87%, and 93%, respectively. In relation to stone diameter size, ureteroscopy obtained significantly better results than ESWL (distal ureteric stones, less 10 mm 97% v 86%, >10 mm 93% v 74%; proximal ureteric stones, >10 mm 81% v 70%). However, since the success rates are so high, patients can opt for the less invasive option of ESWL if available. ESWL may be better for proximal stones smaller than 10 mm. A recent Cochrane review concluded that ureteroscopy had a better stone free rate but a longer hospital stay and greater risk of complications than ESWL.34 Only rarely would other more invasive surgical options be used, such as percutaneous antegrade ureteroscopy (involving direct puncture into the kidney) or laparoscopy, which is usually reserved for large stones (>15 mm), and only if other options have failed or are not suitable.
Tips for non-specialists
- Exclude non-stone causes in patients presenting with renal colic
- Evaluate for signs of sepsis in patients presenting with renal colic
- Provide adequate analgesia using NSAIDs initially, and titrate up the analgesic ladder (avoiding pethidine) according to pain
- Pain free patients without signs of sepsis or red flags for admission (boxes 1 and 2) can be managed in an outpatient setting
- Liaison with local radiology department may be required to organise appropriate and timely imaging if patients are managed outside the hospital setting; based on the limited available evidence, our opinion is that this should be within seven days and ideally sooner
A patient’s perspective
My first experience of renal colic occurred when I was about 20 years old, and it was completely shocking as I had never experienced pain so severe. As well as the intense physical pain in my lower back, which came in waves, there was the added psychological aspect that I did not know what was going on, but knew that it was very serious. The intensity of the associated nausea and vomiting seemed to be amplified by this “fear factor.” In the emergency department, the doctor gave me morphine, after which I fell asleep and the symptoms had passed when I awoke. When riding on my motorcycle the next day, I felt an urgent need to urinate and I passed a small stone. Although this experience left me in fear of renal colic, the subsequent episodes have never had the intensity of the first; they were very unpleasant but I knew what was going on. As I have travelled a lot in the intervening period, including to some areas with poor healthcare, I always carry diclofenac and tramadol with me for emergencies, and I have learnt the importance of always drinking enough fluid.
Questions for future research
- What is the role of medical expulsive therapy? (Ongoing trial by the National Institute for Health Research, SUSPEND (spontaneous urinary stone passage enabled by drugs)
- What is the best surgical intervention for ureteric stones? (Future trial proposed by National Institute for Health Research trial to compare extracorporeal shockwave lithotripsy with ureteroscopy, TISU (therapeutic intervention for stones in the ureter)
- Is retrograde stenting or insertion of percutaneous nephrostomy the best form of drainage in an obstructed infected kidney?
Should All Adults Take a Daily Aspirin?
March 23, 2015
SHOULD ALL ADULTS TAKE A DAILY ASPIRIN
The medical guidelines surrounding aspirin therapy can be confusing. Most doctors agree that an aspirin a day is a good idea for people who already have had a heart attack or stroke, but opinions differ on who, if anyone, should take aspirin to prevent a problem from happening in the first place, a use known as primary prevention. The controversy centers on the painkiller’s blood-thinning properties: While studies have shown that aspirin offers protective benefits against cardiovascular disease and certain cancers, they also have shown that aspirin use can cause bleeding in the stomach and brain.
The question is, do the benefits outweigh the risks for generally healthy people? The Food and Drug Administration doesn’t think so. Some researchers, however, believe the tide will turn in aspirin’s favor once the growing body of cancer evidence is fully evaluated. Jack Cuzick, director of the Wolfson Institute of Preventive Medicine at Queen Mary University of London, argues in favor of general aspirin use, saying the benefit far outweighs the risks; Lianne Marks, assistant dean for educational development and regional chairwoman for internal medicine at Texas A and M Health Science Center College of Medicine, believes the risks are just too great.
YES: The Evidence Is Clear It Reduces Deaths From Cancer. By Jack Cuzick
If you are a middle-aged adult at low risk for bleeding, there is a simple, low-cost way to reduce your chances of dying from cancer and to a lesser extent heart disease: Take a daily baby aspirin. A group of international experts reached that conclusion after conducting a formal benefit/harm analysis on aspirin use in the general population. Our study, published in the Annals of Oncology, found that overall for both men and women aged 50 to 65 the benefits of 10 years of low-dose aspirin outweigh the risks of gastrointestinal bleeding and other complications by a large margin. Specifically, we estimated that daily aspirin could prevent 4% of all deaths in the next 20 years, mostly due to reduced cancer mortality. In terms of cancer prevention, that is exceeded only by avoiding tobacco use and is comparable to reducing obesity but much easier to achieve. Eight deaths from cancer and heart disease would be prevented for every death from gastrointestinal bleeding or stroke. Those are pretty good odds!
Many clinical trials have shown a clear reduction in colorectal cancer from aspirin use, and long-term follow-up of those studies suggests aspirin offers protection against other types of cancers, too. Aspirin seems to have the biggest effect on colorectal, esophageal and stomach cancers, where reductions in excess of 30% were seen both for the development of new cancers and deaths. Smaller but fairly consistent benefits have been reported for lung, prostate and breast cancer, with both incidence and mortality reduced between 10% and 15%. Over 150 observational studies have also confirmed these findings. Why has it taken so long for aspirin’s anticancer benefits to be discovered? The benefits don’t occur right away, so early follow-up of the clinical trials failed to observe them. It is now clear that at least five years of aspirin use is needed for aspirin’s anticancer properties to kick in, and that the benefits are sustained for many years after aspirin use has stopped. How long this carry-over effect lasts needs to be studied further to determine when to stop aspirin, since the bleeding side effects become more serious after age 70.
Aspirin use isn’t without potential side effects, and those who oppose its routine use may cite studies showing higher-than-acceptable rates of bleeding complications to bolster their case. We consider such studies to be outliers. We found serious complications to be rare, with one extra major bleeding event requiring hospitalization occurring for every 300 individuals who take aspirin for 10 years. Aspirin also can increase the incidence of hemorrhagic strokes due to bleeding in the brain, but these events are even more rare and are balanced by a similar reduction in the more common occlusive strokes associated with blood clotting. Still, because hemorrhagic strokes are more often fatal, the small number of people with higher bleeding risks (mostly those with diabetes or hypertension, or who take blood thinners) shouldn’t use aspirin without consulting a doctor.
Changing the equation
When aspirin is evaluated solely in the context of cardiovascular disease, its protective effects are less pronounced, which is why major health organizations don’t recommend it for primary prevention. But the growing body of cancer data tips the benefit-risk calculation strongly in aspirin’s favor, and I expect those recommendations to change once that evidence is fully evaluated. Many things still need to be discovered to refine our use of aspirin for cancer prevention, but that shouldn’t deter people from making use of the clear information we have now.
Video: Professor Peter Elwood and Dr Gareth Morgan discuss the health benefits of Aspirin.
NO: The Risks Are Large, and Increase as a Person Ages. By Lianne Marks
Preventing disease is certainly a noble goal. But before you start taking aspirin to ward off a first heart attack, stroke or cancer, as some suggest, consider this: Evidence-based medicine is increasingly revealing harms in many seemingly safe preventive measures, and aspirin therapy is no exception. New data show that the benefit of taking aspirin to prevent the onset of disease is smaller and the risk greater than previously suspected. Many people consider aspirin to be a relatively benign painkiller, but the complications associated with regular use can be significant, and they increase as a person ages. Daily aspirin can cause gastrointestinal bleeding serious enough to cause hospitalization, as well as fatal hemorrhagic strokes caused by bleeding in the brain. Based on the available evidence, routine aspirin use is best avoided. Instead, it should be an individualized decision discussed with a physician and based on a person’s specific risks.
Paying a price
A study published in the journal Heart in December found that if your risk of coronary artery disease or colon cancer is low, your chance of benefiting from daily aspirin is very low, too. The study examined 28,000 women over 15 years randomized to take low-dose aspirin (100 milligrams every other day) or placebo. The women’s average age at the onset of the trial was 55. Researchers found that the women taking aspirin had a slightly lower risk of cardiovascular disease (371 would have to regularly take the drug to ward off one cardiovascular complication) and colon cancer (709 women would have to take aspirin to prevent one case of colon cancer). But those benefits came at the expense of serious side effects: The estimation was that for every 133 women on aspirin, one would suffer a major bleeding episode (requiring hospitalization), and one out of 29 would have milder bleeding. The authors concluded that for most women, the risk of aspirin outweighs the benefit.
What about diabetic patients and others with higher levels of risk? Several studies have shown no benefit here, either. Research published in December looked at individuals age 60 or older with multiple cardiovascular risk factors and found no benefit from aspirin. In both the aspirin and no-aspirin groups, 56 fatal events occurred in almost 15,000 individuals with a median follow-up of five years. (The study was stopped early as a result.) Older studies produced similar results. A 2012 meta-analysis study that looked at more than 100,000 individuals over six years concluded that in patients with no history of cardiovascular disease, there was no significant benefit of aspirin in reducing deaths from cardiovascular disease or cancer. But there was a significantly increased risk (1 out of 73) of clinically relevant bleeding.
As for aspirin’s role in cancer prevention, a recent paper in Annals of Oncology came out in favor of it. But three of the study’s co-authors said that because the evidence linking aspirin to reductions in breast, prostate and lung cancers is limited, they favor an analysis that includes only reductions in colorectal, esophageal and stomach cancers. Done that way, the analysis shows fewer people helped but the same number harmed. The widespread use of screening tests like colonoscopies also needs to be considered, as that may abrogate aspirin’s protective effects, if present.
In short, for most people, the risks related to aspirin are just too great to justify routine use.
Dr. Marks is assistant dean for educational development and regional chairwoman for internal medicine at Texas A&M Health Science Center College of Medicine in Round Rock, Texas, and an internist with Baylor Scott & White Health.