Acute Loin Pain: Stones,Scopes,Shocks and Stents

Incidence/prevalence

The incidence of urolithiasis is increasing in all demographic groups (i.e. age, sex and race) around the world, such that its prevalence in the USA has doubled in the last 40 years; in the year 2000, its incidence there was 1116/100,000 18 to 64 year olds, with a peak incidence between 40 and 49 years old [1]. Although the incidence of stone disease begins to fall after this age, the cumulative risk of stone formation continues such that by the age of 70, 11% men and 5.6% women will have had a kidney stone diagnosed [2]. It is well established that more men form stones than women, and there are race related risks with Asians having the lowest risk, followed by Blacks, Hispanics, and Caucasians having the greatest risk of becoming a stone former [1,2].

Not only is it common to develop a stone, there is also a high chance of recurrence, ranging from 27% of a symptomatic recurrence after mean follow up of seven and a half years, increasing by a further 28% if asymptomatic stones detected by ultrasound are included [3].

Diagnostic investigations

The role of the non-contrast CTKUB has become well established as the imaging modality of choice for acute ureteric colic due to its rapidity, avoidance of contrast, and the potential to identify other non-stone related causes of abdominal pain. CT is also valuable for its sensitivity, including the ability to identify stones that are genuinely radiolucent on plain films (e.g. those of uric acid composition) or those that cannot be seen due to their small size, or position overlying bone [4].

However, stone formers tend to be young, and have a substantial likelihood of a recurrent episode: increasing awareness of radiation risk, both by clinicians and patients, means that it is important to think twice before arranging this test, particularly in follow-up investigations.

Indeed, a study at St George's Hospital, London demonstrated the median total effective radiation dose of 60 patients rendered stone free from a median stone burden of 4mm was 5.3 mSv (range 1.18–37.66 mSv), with higher doses associated with renal and proximal ureteric stones [5].

In a similar US multicenter study, patients with acute colic typically underwent four further radiographic investigations over the following year, with a median total radiation dose of 29.7 mSv per patient. On average, this comprised 1.2 KUBs (range 0–7), 1.7 CTKUBs (range 0–6) and 1 IVU (range 0–3). [6] The number, location and composition of stones, the type of intervention and the patient's age and sex did not predict the risk of exceeding the recommended annual occupational radiation limit (50 mSv according to the International Commission on Radiological Protection [7]), which was breached in one fifth of the patients in this study [6].

The mainstay of reducing the radiation dose has traditionally been the KUB X-ray, which retains a role for accurate measurement of stone size (which can be overestimated by CT), and during follow up for assessing spontaneous passage or the response to treatment. In this regard, demonstrating a radiolucent stone may lead to a change in management (e.g. from ESWL to URS), due to potential difficulty localising the stone for treatment, and subsequently in confirming a post-treatment stone free state [8].

In fact, a KUB X-ray is not necessary in every patient who presents with possible ureteric colic, or at least, not until the diagnosis is confirmed. Kennish et al. demonstrated that only one half of patients presenting with classical symptoms actually had a stone on CTKUB (61/120 patients analysed i.e. 50.8%). Patients who had already undergone a KUB X-ray before a negative CT had therefore had an unnecessary test, which amounted to 38% of the patients in their series [9].

The need to perform a KUB X-ray after a positive diagnosis by CT to aid follow up can be further reduced by use of the CT scout image. In a retrospective review of 108 patients with confirmed ureteric colic, Johnston et al. found that three quarters of the stones that were visible on KUB X-ray had also been visible on the CT scout image. Although plain film imaging detected some additional radiodense stones that were not visible on the scout image, every stone seen on the scout image was visible on the KUB X-ray [10].

The logical approach is therefore to perform a low dose non-contrast CT KUB as the initial investigation and to examine the scout film of any positive scan to predict stone visibility on KUB X-ray. Only those patients with a stone on CT, which cannot be seen on the scout, need a plain film, since approximately one third of these will show a radio-dense stone and therefore also allow plain film follow up [10].

If CT must be performed for follow-up imaging, then reducing the dose is worthwhile, especially since there is no advantage for increased soft tissue resolution once the diagnosis has been confirmed. Using decreasing doses (140, 100, 60, 30, 15 and 7.5 mAs) to detect calcium oxalate stones measuring 3–7mm that had been placed in the distal ureters of cadaveric models, Jellison and colleagues demonstrated a sensitivity of 98% and specificity 83% for stone detection at any mAs, thereby allowing the radiation dose to be reduced by up to 95% whilst maintaining stone detection rates [11].

The alternative to “ultra-low dose” CT is to avoid ionising radiation altogether with ultrasound. In a prospective study, Passerotti et al. investigated 50 children by both ultrasound and CT, and demonstrated that US had 76% sensitivity (the average size of missed stones was 2.3 mm). Whenever stones were seen on ultrasound, they were confirmed on CT, giving ultrasound 100% specificity. Furthermore, the clinical decisions based on ultrasound were unchanged in 92%: in those that were changed based on the CT result, the ultrasound appearances had recommended additional imaging [12].

These conclusions are supported by Pichler et al, who demonstrated the overall stone detection rate using US was 86.4% (including stones <5mm in size in all positions of the ureter) increasing to 96.4% in adults younger than 35. Body mass index was a significant factor in ultrasound detection rates, such that no patient under 35 with a BMI ≤24kg/m² needed a CT to detect their ureteric stone [13].

These studies confirm that CT is the more sensitive test, but also that ultrasound is particularly valuable in younger patients, for whom a reduced radiation dose is especially important. The clinical relevance of any improved detection of small stones by CT over ultrasound should be considered before arranging a CT, particularly in children [12,13].

Finally, CT at initial assessment brings the potential for over-diagnosis through the detection of small renal stones that may not have been the cause of the acute presentation. Based on evaluation of 5047 patients undergoing CT colonography, the overall prevalence of asymptomatic renal stones was 7.8% (males>females 9.7% vs 6.3%, with an average of 2.1 stones per patient (range 1–29), and mean stone size of 3.0mm (range 1–20) at a mean age of 56.9). An increase in the amount of CT-based imaging is likely to lead to an increased referral of incidental urinary calculi. In their study, Boyce et al. noted that during follow up of up to 10 years, approximately one fifth of the stone-bearing patients had a symptomatic episode (81/395 patients, representing 1.6% of the total population studied). Diabetes and obesity were significant risk factors for symptom development [14].

Whether, and when to intervene

There are a number of factors to consider when deciding whether a patient can be managed expectantly, anticipating spontaneous stone passage, or whether more active intervention is required, what form this should take, and if this is necessary urgently or more electively. The five main factors governing these decisions are the presence of infection proximal to the stone, the risk of renal impairment, the degree of symptoms, the likelihood of spontaneous stone passage, and confirmation (or not) that the patient is stone free after appropriate imaging and follow-up.

The risk of infection

Infection proximal to an obstructing stone is a serious complication due to the risk of gram negative uro-sepsis, which can be potentially life threatening as well as accelerating the loss of that kidney's function. In these circumstances, the collecting system should be drained, antibiotics continued until the infection has resolved, and the stone treated as the final step when the patient has recovered from the acute episode [15].

According to Pearle et al's randomised study comparing percutaneous nephrostomy or JJ stent insertion in patients with obstructing ureteric calculi and features of infection (defined as a temperature > 38 °C or a white blood count > 17,000 mm⁻³), there was no difference in the time taken for temperature to resolve to ≤37.4°C (2.3 days for nephrostomy vs 2.6 for stent), white blood count to reduce to ≤10,000 mm³ (2 days vs 1.7 days) nor in length of stay (4.5 days vs 3.2 days). However, it is important to consider these data in the context of a small study (42 patients), and where positive pre-intervention (52.4% vs 23.8%) and post intervention urine cultures (69.9% vs 19.1%) were disproportionately greater in the patients undergoing nephrostomy than those who were stented [16].

The EAU guidelines support either option for drainage [15], but at UCH (as in most UK units where the circumstances permit), nephrostomy insertion is the preferred choice for the advantages of a large caliber drainage tube (up to 12 Fr compared to a standard 6Fr JJ stent), whilst avoiding the need for general anaesthesia and the risk of ureteric trauma in attempting to bypass a potentially impacted stone. External drainage also allows the output of the obstructed kidney to be monitored, both by volume and appearance. Whilst less practical than a stent, this is less of an issue during the period that the patient requires in-patient care regardless of the position of the tubing, and can be converted to the greater convenience of an antegrade stent before undergoing intervention electively after further recovery at home.

The concern for renal impairment

Impending renal failure is the worrying consequence of inactivity if there is a stone obstructing a solitary kidney, acute colic in a patient with pre-existing chronic renal impairment, or bilateral ureteric stones. In these cases, the more immediate results of ureteroscopy and the potential for leaving a stent, make this a more favourable option than ESWL, particularly as it is possible to treat both sides at one sitting by ureteroscopy.

Although bilateral ureteroscopy might be anticipated to be a risk factor for adverse results, El-Hefnawy et al. investigated 89 patients treated with bilateral ureteroscopy, and reported a successful outcome (defined as both ureters stone free without any intra-operative complications) in 70% of patients. Risk factors for an unsuccessful procedure included impacted (RR 3.6), large (RR 1.47) proximal ureteric (RR 3.3) stones. Interestingly, compared to 105 unilateral ureteroscopic procedures, the intra-operative complication rate was equivalent at 6.2% (bilateral) vs 6.7% (unilateral); as was the stone free rate 86% (bilateral) vs 80% (unilateral) [17].

The degree of symptoms

Active intervention can only be deferred if the patient's pain can be adequately managed without injectable analgesia. Assuming there are no contraindications, the best first-line analgesia for ureteric colic is a non-steroidal anti-inflammatory drug (NSAID), as concluded by Holdgate and Pollock's Cochrane review of 20 randomized controlled trials that compared NSAIDs with opiate analgesia. They reported no difference in complete pain relief for either analgesic, but noted that supplementary analgesia was needed more often in patients receiving opiates as the initial medication (25.4 versus 18.9%). Since patients randomized to opiates, especially pethidine, were more likely to suffer with vomiting (19.5 versus 5.8%), using NSAIDs with equivalent analgesic effect and less side effects makes good sense [18].

Unfortunately, the common practice of encouraging a high fluid intake to “flush out the stone” may be fallacious. Glen Preminger's team found that patients given 2L forced hydration over 2h had no difference in analgesic requirement, pain score nor stone-passage rates compared with patients on a minimal maintenance regimen [19].

A patient who cannot be made comfortable, including due to uncontrollable nausea and vomiting, should be offered emergency active treatment.

The likelihood of spontaneous stone passage

Morse and Resnik demonstrated an overall spontaneous passage rate of 60% for ureteric calculi, but found the more proximal the stone, the less likely it would pass spontaneously. Although nearly three quarters (71%) of distal stones passed spontaneously, half (46%) of mid ureteric and less than a quarter (22%) of proximal ureteric stones did so [20].

A cut-off of 5 mm is also useful in predicting stone passage: a meta-analysis in the EAU guidelines of 2009 showed that 68% of stones ≤5mm passed spontaneously, reducing to 47% for stones between 5 and 10mm [15]. Furthermore, stones larger than 5mm have been shown to be more likely to cause obstruction, drop in relative renal function and require subsequent intervention [21].

The speed at which spontaneous passage occurs

In another classic study based on 143 ureteric stone patients monitored with renography, Holm-Nielsen et al. demonstrated that the longer the stone remained in situ, the greater the chance of reduced renal function. They reported 100% recovery of renal function by renography for stones passed within 14 days, 82% recovery if obstruction was relieved within 15–28 days, but just 65% recovery if the kidney was left obstructed for longer than 28 days. As already commented on above, they reported that infection proximal to ureteric stones accelerated kidney damage substantially [22].

Smaller stones are not only more likely to pass, they tend to do so more quickly, as demonstrated by Miller and Kane, who reported that stones ≤2mm, 2–4mm and 4–6mm that passed spontaneously tended to do so by 31, 40, and 39 days, respectively [23].

Since these studies were performed, the observation of ureteric stones has been changed by the addition of medical expulsive therapy (MET), which has now been evaluated in a number of meta-analyses. The first of these was reported in the Lancet in 2006 by Hollingsworth et al, who summarised nine RCTs using Ca-channel blockers or alpha blockers in acute ureteric colic up to July 2005. Their data demonstrated a 65% greater chance of stone passage with expulsive therapy, with a number needed to treat of 4 [24]. By 2007, 25 studies of MET were available for evaluation, with a relative risk for alpha blockers of 1.59 (NNT 3.3) and 1.50 (NNT 3.9) for calcium channel blockers. This study showed fewer side effects with alpha blockers (4%) compared with calcium channel blockers (15.2%) [25]. By the end of 2008, 47 RCTs assessing MET were reviewed by Seitz et al, who reported a higher and faster expulsion rate seen with MET (alpha-blocker and calcium channel blocker data were pooled) compared to controls. In addition, analgesia consumption, episodes of colic, and hospital attendances were also reduced [26].

The EAU guidelines also included a meta-analysis of MET, concluding that alpha blockers showed a statistically significant absolute increase of 29% in the stone-passage rate versus control. They concluded that patients with ureteric stones less than 10mm with well controlled symptoms could reasonably be offered MET whilst awaiting stone passage provided appropriate monitoring and follow-up was arranged (i.e. to demonstrate stone progression and absence of hydronephrosis) [15].

These analyses all agreed that the majority of randomised studies analysed were small, single-centre studies, and that a high-quality, multicentre, randomised, placebo-controlled trial was still needed to confirm the role of MET in acute colic [15,24 -26].

Finally, it is important to emphasise that patients should be informed that MET is an “off label” use for the medication, particularly for females prescribed alpha-blockers in which the product information or internet search is likely to cause considerable confusion about their prostate symptoms…

Active treatment

Large, proximal stones take longer to pass, if they do so at all, and carry a risk to renal function whilst waiting, as well as the potential for recurrent symptoms or readmission. For these reasons, it may be better to offer patients with large stones active intervention sooner rather than later. The EAU guidelines state that “both SWL and URS should be discussed as initial treatment options for the majority of cases”. Like the chances of spontaneous passage discussed above, the choice of treatment depends primarily on the site and size of the stone, with ureteroscopy generally having a slight edge over ESWL for all stone sizes below the iliac vessels. In the proximal ureter, ESWL has a better stone free rate than URS for stones less than 10mm in size (the only site/size combination where it out-performs ureteroscopy, at 90% vs 80%), which is reversed in favour of URS for stones more than 10mm (79% for URS vs 68% with ESWL) [15].

The choice between these may also be influenced by the potential for complications from the treatment – ESWL having the convenience of an out-patient based procedure avoiding general anaesthesia, but with the potential need for repeated treatments, and the chance of colic from the passage of fragments, including the risk of ureteric steinstrasse. However, the main advantage of ESWL is its much lower likelihood of requiring a JJ stent – a key consideration if the patient has ever had one before (see below) and the fact that complications from ureteroscopy can be more serious than those associated with ESWL, although improvements to instruments continue to reduce the incidence of ureteric perforation to less than 5%, and stricture rates are less than 2% [27]. In a retrospective review of 442 ureteroscopic procedures, Abdelrahim et al. identified a 27% chance of an intra-operative adverse event, of which 45% were due to stone migration and 20% accounted for by minor mucosal injuries. More serious adverse events were less common, with 10% due to ureteric perforation and 1.7% risk of ureteric avulsion (representing 2.7% and 0.5% of cases overall respectively). 24% of adverse cases (6.6% of the cases overall) were abandoned (due to bleeding or oedema) [28].

Complications common to both ESWL and ureteroscopy include Urinary Tract Infection, and the potential for leaving of a residual fragment (RF), with the risk of this enlarging and requiring further treatment, or passing spontaneously in an episode of ureteric colic. In an often quoted study of post ESWL RF, each of these outcomes for a residual stone was equally likely: after median follow up 40.6 months post ESWL, 29% of patients with RF remained stable, 37% had increased in size, and 33% became stone free [29]. A similar study based on 173 patients post ESWL with residual fragments ≤4mm reported a slightly lower rate of symptom recurrence and the need for repeat treatment of 21.4%. Those patients who passed stones spontaneously generally did so within a few weeks, and were then untroubled by recurrent symptoms [30]. These data are mirrored by a study of RF ≤4mm followed for 19 months after ureteroscopy, in whom 19.6% of patients had a “stone event” (A/E visit/admitted or an additional intervention) and a further 21.7% had spontaneous fragment passage. In this series, the remaining 58.7% continued to be asymptomatic with stones remaining stable in size [31].

In the end, a “residual fragment” is simply a stone by another name, and therefore behaves the same whether it was created by ESWL, ureteroscopy, or was identified incidentally. Although many patients with RF will remain asymptomatic, residual stones carry a risk of further problems, particularly if the fragment was located in the renal pelvis or ureter, had a maximum diameter >2mm or where there were multiple fragments, and therefore a larger total residual stone burden [32].

Whereas ESWL necessarily leaves fragments for spontaneous passage (perhaps with the addition of MET to facilitate this), ureteroscopy offers the opportunity for active removal of stone fragments. However, this carries the added cost of the basket/retrieval device, as well as the potential cost to the ureter through additional oedema or direct trauma from repeated instrumentation. The two distinct techniques of “paint and dust” (i.e. vaporising the stone as much as possible into tiny, powder-like fragments, which are difficult to grasp, but ideal for spontaneous drainage) against a “smash and grab” approach (fragmenting the stone into 3–4mm pieces and removing these under vision) therefore have to be considered as part of the overall treatment strategy. Furthermore, the possibility of loss of small fragments to the kidney under irrigation may be minimised by the use of a device to reduce stone migration [33,34], or resolved after the stone has been treated by flexible ureterorenoscopy.

Coining the term “favourable result” for ureteroscopy (defined as being stone-free in a single procedure with no complications), El-Nahas et al. retrospectively analysed 841 patients undergoing 908 ureteroscopic procedures for ureteric stones. There was an 87% stone-free rate after a single URS, and a 6.7% complication rate, with a combined chance of 82.7% for a “favourable result”. The most significant risk factor for unfavourable results was stone location in the proximal ureter (RR 4), followed by surgical inexperience (RR 2.5), stone impaction (RR 1.8) and stone width (RR 1.2) [35].

Having identified a potentially challenging case raises the question whether to pre-stent the patient in anticipation of complications. In a retrospective study comparing single-phased versus 2-phased ureteroscopy, success was increased from 86.9% in de novo treated stones to 97.3% in patients who had been pre-stented, although this was not statistically significant [36].

The clear advantage of ureteroscopy over ESWL for ureteric stones is the potential to perform a flexible ureterorenoscopy at the same time. Based on a review of 112 patients having URS for ureteric stones with a mean size of 8mm, 63 also had FURS for concomitant renal stones, which increased the operative time by an average of 18min. The overall complication rate was equivalent (3.1% for ureteroscopy and flexible ureterorenoscopy vs 2.5% for ureteroscopy alone). The authors of this study noted that the stone free rates decreased with larger renal stones, and therefore recommended this for ipsilateral renal calculi smaller than 15 mm [37].

Stents

All urologists know that stents can cause bothersome symptoms. As clearly demonstrated in Joshi et al's key paper of 2003, more than 80% of patients suffered stent symptoms that affected their day-to-day life. The commonest side effect (in nearly four fifths of patients) was bothersome urinary symptoms, primarily storage symptoms including incontinence, and haematuria. More than half of patients have reduced ability to return to work, and just under a third experience some sexual dysfunction [38].

Numerous methods to reduce discomfort have been tried, including various evolutions of stent design, such as softening the distal end of the stent with the goal of reducing bladder irritation. Although this type of stent caused slightly less haematuria (without reaching significance), there was no difference in stent symptoms in a randomised trial [39].

A similar study comparing four different types of stent (short and long “loop tailed” stents, the Percuflex Plus stent and the Polaris stent) showed characteristic stent symptoms in all, including flank pain (47%), haematuria (39%), dysuria (34%), frequency (30%) and urgency (27%). Pain worsened from baseline to day 4 (although the use of analgesics peaked on day 1, suggesting a degree of acceptance of the symptoms) and improved again from day 4 until stent removal after 30 days [40].

In an attempt to minimise pain, ketorolac drug-eluting stents have been tried, but unfortunately a randomised study comparing these against control stents showed no difference in pain visual analogue score, nor in the likelihood of an unscheduled consultation or early stent removal [41].

Oral medication with oxybutynin or phenazopyridine (an oral agent that has a local anaesthetic effect through being excreted in the urine) is no more effective, providing no advantage over placebo for flank pain, suprapubic pain, urinary frequency, urgency nor dysuria in a prospective, randomized, double-blind trial of patients with a unilateral stent after ureteroscopy. Phenazopyridine was associated with an earlier resolution of haematuria, and those on oxybutynin tended to use less opioid analgesia (but this did not reach statistical significance) [42].

The best hope for relieving stent symptoms may come from alpha blockers: there are now two metaanalyses for the use of alpha blockers in alleviating stent symptoms. The rationale for this is through their reduction in smooth muscle activity, and therefore reducing stent pain from ureteric smooth muscle spasm. In the study from Cambridge, five randomized controlled trials were analysed, and the urinary symptom score showed a mean reduction of 8.4, with a reduction in the body pain score of 7.2 (as assessed by the Ureteral Stent Symptom Questionnaire). Patients receiving an α-blocker experienced less painful episodes (45% compared to 76% of controls, a risk reduction of 0.59) [43].

These findings were mirrored in a similar study that identified 12 randomized controlled trials comparing alpha-blockers against placebo, although only four of these were adequate for the metanalysis. Given the overlap in data, the results are similar with α-blockers showing a significant decrease in urinary symptoms (6.8 point reduction) and pain (a 3.6 point reduction), but not with a benefit for return to work nor in sexual function. In this study, seven of the eight studies not analysed were also noted to have shown a significant decrease in urinary symptoms and pain [44].

Overall, the attempts to make stents more tolerable have been disappointing, and therefore the best way to reduce stent symptoms is to avoid stent insertion in the first place. The insertion of a stent should therefore be an active decision, rather than a “routine” step of ureteroscopic treatment. Although there are clearly circumstances in which stenting is sensible (including ureteric injury, the presence of a stricture, surgery on a solitary kidney or background of renal impairment, or a large residual stone burden requiring a “2nd Look” treatment), it is also increasingly appreciated that stents may not be required in “uncomplicated cases”.

This has been demonstrated in a meta-analysis of nine RCTs (including 831 patients) of stented versus un-stented ureteroscopy, which confirmed that performing a stent-free ureteroscopy was not associated with an adverse affect on the stone free rate, likelihood of urinary tract infection, nor on the requirement for analgesia. Most reassuringly, there was no difference in the long term risk of developing a ureteric stricture. However, the authors commented that poor data quality means the role of stents after uncomplicated ureteroscopy remains unresolved, not least as the definition of “uncomplicated” ureteroscopy is unclear [45].